Respiratory problems in patients with ectodermal dysplasia syndromes.

PubMed

Fete, Timothy

2014-10-01

The ectodermal dysplasias (EDs) are a heterogeneous group of disorders characterized by a deficiency of ectoderm- and mesoderm-derived tissues and appendages, particularly hair, skin, teeth, and nails. Many of these disorders are associated with a greater risk of respiratory disease than found in the general population. There are no published papers that comprehensively describe these findings and the possible etiologies. Patients have been reported with dramatic decrease in mucous glands in the respiratory tract. Anatomic defects, including cleft palate, that predispose to respiratory infection, are associated with several of the ED syndromes. Atopy and immune deficiencies have been shown to have a higher prevalence in ED syndromes. Clinicians who care for patients affected by ED syndromes should be aware of the potential respiratory complications, and consider evaluation for structural anomalies, atopy and immunodeficiency in individuals with recurrent or chronic respiratory symptoms. © 2014 Wiley Periodicals, Inc.

The origin and evolution of the ectodermal placodes

PubMed Central

Graham, Anthony; Shimeld, Sebastian M

2013-01-01

Many of the features that distinguish the vertebrates from other chordates are found in the head. Prominent amongst these differences are the paired sense organs and associated cranial ganglia. Significantly, these structures are derived developmentally from the ectodermal placodes. It has therefore been proposed that the emergence of the ectodermal placodes was concomitant with and central to the evolution of the vertebrates. More recent studies, however, indicate forerunners of the ectodermal placodes can be readily identified outside the vertebrates, particularly in urochordates. Thus the evolutionary history of the ectodermal placodes is deeper and more complex than was previously appreciated with the full repertoire of vertebrate ectodermal placodes, and their derivatives, being assembled over a protracted period rather than arising collectively with the vertebrates. PMID:22512454

KDF1, encoding keratinocyte differentiation factor 1, is mutated in a multigenerational family with ectodermal dysplasia.

PubMed

Shamseldin, Hanan E; Khalifa, Ola; Binamer, Yousef M; Almutawa, Abdulmonem; Arold, Stefan T; Zaidan, Hamad; Alkuraya, Fowzan S

2017-01-01

Ectodermal dysplasia is a highly heterogeneous group of disorders that variably affect the derivatives of the ectoderm, primarily skin, hair, nails and teeth. TP63, itself mutated in ectodermal dysplasia, links many other ectodermal dysplasia disease genes through a regulatory network that maintains the balance between proliferation and differentiation of the epidermis and other ectodermal derivatives. The ectodermal knockout phenotype of five mouse genes that regulate and/or are regulated by TP63 (Irf6, Ikkα, Ripk4, Stratifin, and Kdf1) is strikingly similar and involves abnormal balance towards proliferation at the expense of differentiation, but only the first three have corresponding ectodermal phenotypes in humans. We describe a multigenerational Saudi family with an autosomal dominant form of hypohidrotic ectodermal dysplasia in which positional mapping and exome sequencing identified a novel variant in KDF1 that fully segregates with the phenotype. The recapitulation of the phenotype we observe in this family by the Kdf1-/- mouse suggests a causal role played by the KDF1 variant.

Localization of Brachyury (T) in embryonic and extraembryonic tissues during mouse gastrulation.

PubMed

Inman, Kimberly E; Downs, Karen M

2006-10-01

T-box gene family members have important roles during murine embryogenesis, gastrulation, and organogenesis. Although relatively little is known about how T-box genes are regulated, published gene expression studies have revealed dynamic and specific patterns in both embryonic and extraembryonic tissues of the mouse conceptus. Mutant alleles of the T-box gene Brachyury (T) have identified roles in formation of mesoderm and its derivatives, such as somites and the allantois. However, given the cell autonomous nature of T gene activity and conflicting results of gene expression studies, it has been difficult to attribute a primary function to T in normal allantoic development. We report localization of T protein by sectional immunohistochemistry in both embryonic and extraembryonic tissues during mouse gastrulation, emphasizing T localization within the allantois. T was detected in all previously reported sites within the conceptus, including the primitive streak and its derivatives, nascent embryonic mesoderm, the node and notochord, as well as notochord-associated endoderm and posterior neurectoderm. In addition, we have clarified T within the allantois, where it was first detected in the proximal midline of the late allantoic bud (approximately 7.5 days postcoitum, dpc) and persisted within an expanded midline domain until 6-somite pairs (s; approximately 8.5 dpc). Lastly, we have discovered several novel T sites, including the developing heart, visceral endoderm, extraembryonic ectoderm, and its derivative, chorionic ectoderm. Together, these data provide a unified picture of T in the mammalian conceptus, and demonstrate T's presence in unrelated cell types and tissues in highly dynamic spatiotemporal patterns in both embryonic and extraembryonic tissues.

Co-ordinated ocular development from human iPS cells and recovery of corneal function.

PubMed

Hayashi, Ryuhei; Ishikawa, Yuki; Sasamoto, Yuzuru; Katori, Ryosuke; Nomura, Naoki; Ichikawa, Tatsuya; Araki, Saori; Soma, Takeshi; Kawasaki, Satoshi; Sekiguchi, Kiyotoshi; Quantock, Andrew J; Tsujikawa, Motokazu; Nishida, Kohji

2016-03-17

The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.

Tissue-specific Requirements of β-Catenin in External Genitalia Development

PubMed Central

Lin, Congxing; Yin, Yan; Long, Fanxin; Ma, Liang

2008-01-01

SUMMARY External genitalia are body appendages specialized for internal fertilization. Its development can be divided into two phases, an early androgen-independent phase and a late androgen-dependant sexual differentiation phase. In the early phase, the embryonic anlage of external genitalia, the genital tubercle (GT), are morphologically identical in both sexes. Although congenital external genitalia malformations represent the second most common birth defect in humans, the genetic pathways governing early external genitalia development and urethra formation are poorly understood. Proper development of the GT requires coordinated outgrowth of the mesodermally-derived mesenchyme and extension of the endodermal urethra within an ectodermal epithelial capsule. Here we demonstrate that β-Catenin plays indispensable and distinct roles in each of the aforementioned three tissue layers in early androgen-independent GT development. WNT-β-Catenin signaling is required in the endodermal urethra to activate and maintain Fgf8 expression and direct GT outgrowth, as well as to maintain homeostasis of the urethra. Moreover, β-Catenin is required in the mesenchyme to promote cell proliferation. In contrast, β-Catenin is required in the ectoderm to maintain tissue integrity possibly through cell-cell adhesion during GT outgrowth. The fact that both endodermal and ectodermal β-Catenin knockout animals develop severe hypospadias in both sexes raises the possibility that deregulation of any of these functions can contribute to the etiology of congenital external genital defects in humans. PMID:18635608

Ectodermal Dysplasia: A Case Report

PubMed Central

2011-01-01

Ectodermal dysplasia is a hereditary disease characterized by dysplasia of tissues of ectodermal origin. The incidence of ectodermal dysplasia is rare (1 in 100,000 birth). This case report discusses the features, classification and prosthetic treatment plan (upper partial denture and lower complete denture for upper partial and lower complete edentulous arches respectively). This treatment plan would be able to provide psychological and functional boost to the sufferer. PMID:27678241

EDA mutation as a cause of hypohidrotic ectodermal dysplasia: a case report and review of the literature.

PubMed

Huang, S X; Liang, J L; Sui, W G; Lin, H; Xue, W; Chen, J J; Zhang, Y; Gong, W W; Dai, Y; Ou, M L

2015-08-28

Ectodermal dysplasia (ED) represents a collection of rare disorders that result from a failure of development of the tissues derived from the embryonic ectoderm. ED is often associated with hair, teeth, and skin abnormalities, which are serious conditions affecting the quality of life of the patient. To date, a large number of genes have been found to be associated with this syndrome. Here, we report a patient with hypohidrotic ED (HED) without family history. We identified that this patient's disorder arises from an X-linked HED with a mutation in the EDA gene (G299D) found by whole-exome sequencing. In addition, in this paper we summarize the disease-causing mutations based on current literature. Overall, recent clinical and genetic research involving patients with HED have uncovered a large number of pathogenic mutations in EDA, which might contribute to a full understanding of the function of EDA and the underlying mechanisms of HED caused by EDA mutations.

Inducible Transgenic Models of BRCA1 Function

DTIC Science & Technology

1998-10-01

development, and for signs of hyperplasia, dysplasia and neoplasia. Specific Aim 3. Inducibly abolish Brcal expression in the mammary epithelium of...abnormalities in mammary epithelial proliferation, differentiation and development, and for signs of hyperplasia, dysplasia and neoplasia. 6...Lyu MS, Kozak CA and Leder P. Expression of Brcal is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice

Müllerian agenesis with hypohidrotic ectodermal dysplasia syndrome.

PubMed

Whaley, Katie; Winter, Jordan; Eyster, Kathleen M; Hansen, Keith A

2012-04-01

To describe the association of müllerian agenesis with hypohidrotic ectodermal dysplasia. Case report. University medical center. A 17-year-old woman with hypohidrotic ectodermal dysplasia referred for evaluation of primary amenorrhea. History, physical examination, and ultrasound. Physical findings of these two syndromes. Physical examination and ultrasound demonstrated müllerian agenesis with findings of hypohidrotic ectodermal dysplasia. This is the first description of the association of müllerian agenesis with ectodermal dysplasia. This rare case might provide further insight into the development of the uterus and the ectoderm as well as its derivatives. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Characterization and expression of amphioxus ApoD gene encoding an archetype of vertebrate ApoD proteins.

PubMed

Wang, Lei; Zhang, Shicui; Liu, Zhenhui; Li, Hongyan; Wang, Yongjun; Jiang, Shengjuan

2007-01-01

Here we report a homologue of the apolipoprotein D gene (AmphiApoD) in amphioxus, Branchiostoma belcheri tsingtauense, the first such finding in a basal chordate cephalochordate. The main features of the protein predicted from AmphiApoD are characteristic of the apolipoprotein D. Phylogenetic analysis places AmphiApoD at the base of the phylogenetic tree, suggesting that AmphiApoD is the archetype of the vertebrate ApoD genes. Both whole mount in situ hybridization and Northern blotting and RT-PCR as well as in situ hybridization histochemistry reveal that AmphiApoD is expressed in tissues derived from mesoderm and endoderm including notochord and hind-gut, which contrasts with the strong expression patterns of ApoD genes in the ectodermal derivatives in mammals and birds. The expression profiles of the ApoD gene may have been changed to be expressed in the endo-mesodermal derivatives in amphioxus after the vertebrate and cephalochordate lineages diverged; alternatively, the ApoD gene may first have been expressed in the endo-mesoderm during embryogenesis in the last common ancestor of all chordates, and subsequently came to be expressed in the ectodermal derivatives of vertebrates including mammals and birds.

Transcriptional Profiling of Ectoderm Specification to Keratinocyte Fate in Human Embryonic Stem Cells

PubMed Central

Tadeu, Ana Mafalda Baptista; Lin, Samantha; Hou, Lin; Chung, Lisa; Zhong, Mei; Zhao, Hongyu; Horsley, Valerie

2015-01-01

In recent years, several studies have shed light into the processes that regulate epidermal specification and homeostasis. We previously showed that a broad-spectrum γ–secretase inhibitor DAPT promoted early keratinocyte specification in human embryonic stem cells triggered to undergo ectoderm specification. Here, we show that DAPT accelerates human embryonic stem cell differentiation and induces expression of the ectoderm protein AP2. Furthermore, we utilize RNA sequencing to identify several candidate regulators of ectoderm specification including those involved in epithelial and epidermal development in human embryonic stem cells. Genes associated with transcriptional regulation and growth factor activity are significantly enriched upon DAPT treatment during specification of human embryonic stem cells to the ectoderm lineage. The human ectoderm cell signature identified in this study contains several genes expressed in ectodermal and epithelial tissues. Importantly, these genes are also associated with skin disorders and ectodermal defects, providing a platform for understanding the biology of human epidermal keratinocyte development under diseased and homeostatic conditions. PMID:25849374

Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.

PubMed

Li, Jing; Wang, Shusheng; Anderson, Chastain; Zhao, Fangkun; Qin, Yu; Wu, Di; Wu, Xinwei; Liu, Jia; He, Xuefei; Zhao, Jiangyue; Zhang, Jinsong

2016-01-01

Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development.

Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development

PubMed Central

Li, Jing; Wang, Shusheng; Anderson, Chastain; Zhao, Fangkun; Qin, Yu; Wu, Di; Wu, Xinwei; Liu, Jia; He, Xuefei; Zhao, Jiangyue; Zhang, Jinsong

2016-01-01

Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development. PMID:27494603

Three-dimensional epithelial tissues generated from human embryonic stem cells.

PubMed

Hewitt, Kyle J; Shamis, Yulia; Carlson, Mark W; Aberdam, Edith; Aberdam, Daniel; Garlick, Jonathan A

2009-11-01

The use of pluripotent human embryonic stem (hES) cells for tissue engineering may provide advantages over traditional sources of progenitor cells because of their ability to give rise to multiple cell types and their unlimited expansion potential. We derived cell populations with properties of ectodermal and mesenchymal cells in two-dimensional culture and incorporated these divergent cell populations into three-dimensional (3D) epithelial tissues. When grown in specific media and substrate conditions, two-dimensional cultures were enriched in cells (EDK1) with mesenchymal morphology and surface markers. Cells with a distinct epithelial morphology (HDE1) that expressed cytokeratin 12 and beta-catenin at cell junctions became the predominant cell type when EDK1 were grown on surfaces enriched in keratinocyte-derived extracellular matrix proteins. When these cells were incorporated into the stromal and epithelial tissue compartments of 3D tissues, they generated multilayer epithelia similar to those generated with foreskin-derived epithelium and fibroblasts. Three-dimensional tissues demonstrated stromal cells with morphologic features of mature fibroblasts, type IV collagen deposition in the basement membrane, and a stratified epithelium that expressed cytokeratin 12. By deriving two distinct cell lineages from a common hES cell source to fabricate complex tissues, it is possible to explore environmental cues that will direct hES-derived cells toward optimal tissue form and function.

Spatial and temporal expression of the Grainyhead-like transcription factor family during murine development.

PubMed

Auden, Alana; Caddy, Jacinta; Wilanowski, Tomasz; Ting, Stephen B; Cunningham, John M; Jane, Stephen M

2006-10-01

The Drosophila transcription factor Grainyhead (grh) is expressed in ectoderm-derived tissues where it regulates several key developmental events including cuticle formation, tracheal elongation and dorsal closure. Our laboratory has recently identified three novel mammalian homologues of the grh gene, Grainyhead-like 1, -2 and -3 (Grhl1-3) that rewrite the phylogeny of this family. Using gene targeting in mice, we have shown that Grhl3 is essential for neural tube closure, skin barrier formation and wound healing. Despite their extensive sequence homology, Grhl1 and Grhl2 are unable to compensate for loss of Grhl3 in these developmental processes. To explore this lack of redundancy, and to gain further insights into the functions of this gene family in mammalian development we have performed an extensive in situ hybridisation analysis. We demonstrate that, although all three Grhl genes are highly expressed in the developing epidermis, they display subtle differences in the timing and level of expression. Surprisingly, we also demonstrate differential expression patterns in non-ectoderm-derived tissues, including the heart, the lung, and the metanephric kidney. These findings expand our understanding of the unique role of Grhl3 in neurulation and epidermal morphogenesis, and provide a focus for further functional analysis of the Grhl genes during mouse embryogenesis.

Multidisciplinary management of hypohydrotic ectodermal dysplasia – a case report

PubMed Central

Joseph, Suja; Cherackal, George J; Jacob, Jose; Varghese, Alex K

2015-01-01

Key Clinical Message Hypohydrotic ectodermal dysplasia is a hereditary disorder, which affects ectodermal derivatives. It manifests several abnormalities of the teeth, and is commonly inherited through female carriers. This case report presents a patient with compromised esthetics and function. A multidisciplinary approach was planned involving an oral pathologist, endodontist, orthodontist and a prosthodontist. PMID:25984305

Individualized Plastic Reconstruction Strategy for Patients With Ectodermal Dysplasia Syndrome.

PubMed

Hou, Yikang; Jin, Yunbo; Lin, Xiaoxi; Chai, Gang; Zhang, Yan; Qi, Zuoliang

2017-06-01

Ectodermal dysplasia syndrome is a hereditary disease of ectodermal origin. Appearances of nail dystrophy, alopecia or hypotrichosis, saddle nose deformity, and palmoplantar hyperkeratosis are usually associated with a lack of sweat glands as well as partial or complete absence of teeth. These manifestations are usually corrected only with oral rehabilitation by mounting dentures. In this study, plastic rehabilitation was developed to correct the special features of patients with ectodermal dysplasia. Four men and 1 woman with ectodermal dysplasia syndrome were treated. Four patients showed dysostosis of the midface, and rhinoplasty with costal bone was performed, whereas cosmetic operation aiming to repair soft tissue defects was adopted for the last patient. After plastic corrections, all 5 patients were satisfied with the results and had no social embarrassment.

[Clinical and molecular study in a child with X-linked hypohidrotic ectodermal dysplasia].

PubMed

Callea, Michele; Yavuz, Izzet; Clarich, Gabriella; Cammarata-Scalisi, Francisco

2015-12-01

Ectodermal dysplasia encompasses more than 200 clinically distinct entities, which affect at least two structures derived from the ectoderm, including the skin, hair, nails, teeth, sweat glands, and sebaceous glands. X-linked hypohidrotic ectodermal dysplasia is the most common type and is caused by mutation of the EDA gene that encodes Ectodysplasin-A. It occurs in less than 1 in 100 000 individuals and is clinically characterized by hypodontia, hypohidrosis, hypotrichosis, and eye dis orders. We present a child evaluated in a multidisciplinary manner with clinical and molecular diagnosis of X-linked hypohidrotic ectodermal dysplasia with type missense mutation c.1133C> T; p.T378M in EDA gene.

Applications of patient-specific induced pluripotent stem cells; focused on disease modeling, drug screening and therapeutic potentials for liver disease.

PubMed

Chun, Yong Soon; Chaudhari, Pooja; Jang, Yoon-Young

2010-12-14

The recent advances in the induced pluripotent stem cell (iPSC) research have significantly changed our perspectives on regenerative medicine by providing researchers with a unique tool to derive disease-specific stem cells for study. In this review, we describe the human iPSC generation from developmentally diverse origins (i.e. endoderm-, mesoderm-, and ectoderm- tissue derived human iPSCs) and multistage hepatic differentiation protocols, and discuss both basic and clinical applications of these cells including disease modeling, drug toxicity screening/drug discovery, gene therapy and cell replacement therapy.

The Neural Border: Induction, Specification and Maturation of the territory that generates Neural Crest cells.

PubMed

Pla, Patrick; Monsoro-Burq, Anne H

2018-05-28

The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions. Copyright © 2018. Published by Elsevier Inc.

Infantile bilateral glaucoma in a child with ectodermal dysplasia.

PubMed

Callea, Michele; Vinciguerra, Agatino; Willoughby, Colin E; Deroma, Laura; Clarich, Gabriella

2013-01-01

Ectodermal dysplasia is a rare disease which affects at least two ectodermal-derived structures such as hair, nails, skin, sweat glands and teeth. Approximately 200 different conditions have been classified as an ectodermal dysplasia and X-linked hypohidrotic ectodermal dysplasia (XHED) represents the commonest form. Clinically, XHED is characterized by hypotrichosis, hypohidrosis and hypodontia. A variety of ocular manifestations have been reported in XHED, the most common being dryness of eyes due to tear deficiency and instability of the film secondary to the absence of meibomian gland function. Here we report a child with the distinctive clinical features of XHED confirmed with molecular diagnosis who presented with infantile bilateral glaucoma, in addition to the classical ocular involvement in XHED.

Clonal and molecular analysis of the prospective anterior neural boundary in the mouse embryo

PubMed Central

Cajal, Marieke; Lawson, Kirstie A.; Hill, Bill; Moreau, Anne; Rao, Jianguo; Ross, Allyson; Collignon, Jérôme; Camus, Anne

2012-01-01

In the mouse embryo the anterior ectoderm undergoes extensive growth and morphogenesis to form the forebrain and cephalic non-neural ectoderm. We traced descendants of single ectoderm cells to study cell fate choice and cell behaviour at late gastrulation. In addition, we provide a comprehensive spatiotemporal atlas of anterior gene expression at stages crucial for anterior ectoderm regionalisation and neural plate formation. Our results show that, at late gastrulation stage, expression patterns of anterior ectoderm genes overlap significantly and correlate with areas of distinct prospective fates but do not define lineages. The fate map delineates a rostral limit to forebrain contribution. However, no early subdivision of the presumptive forebrain territory can be detected. Lineage analysis at single-cell resolution revealed that precursors of the anterior neural ridge (ANR), a signalling centre involved in forebrain development and patterning, are clonally related to neural ectoderm. The prospective ANR and the forebrain neuroectoderm arise from cells scattered within the same broad area of anterior ectoderm. This study establishes that although the segregation between non-neural and neural precursors in the anterior midline ectoderm is not complete at late gastrulation stage, this tissue already harbours elements of regionalisation that prefigure the later organisation of the head. PMID:22186731

Dlx proteins position the neural plate border and determine adjacent cell fates.

PubMed

Woda, Juliana M; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

2003-01-01

The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates.

Death due to complications of anhidrotic ectodermal dysplasia.

PubMed

Ogden, Emily; Schandl, Cynthia; Tormos, Lee Marie

2014-11-01

Ectodermal dysplasia comprises a group of disorders affecting ectodermal tissues. Severity depends on the genetic aberration; hyperpyrexia secondary to absence of sweat glands is a common complication. Treatment is supportive. This case report describes a 1-month, 27-day-old male infant with a diagnosis of X-linked recessive anhidrotic ectodermal dysplasia. On the day of his death, his mother swaddled him in a blanket and placed him on the couch at 5:30 am. When she picked him up at 8:00 am, he was unresponsive. At the emergency department, his rectal temperature was 40°C. Postmortem blood culture was positive for group B streptococcus, a possible etiology for fever. It is vital to teach parents that close monitoring of children with ectodermal dysplasia is necessary, as an increase in body temperature can become life threatening. © 2014 American Academy of Forensic Sciences.

Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration.

PubMed

Ratheesh, Aparna; Biebl, Julia; Vesela, Jana; Smutny, Michael; Papusheva, Ekaterina; Krens, S F Gabriel; Kaufmann, Walter; Gyoergy, Attila; Casano, Alessandra Maria; Siekhaus, Daria E

2018-05-07

Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Dlx proteins position the neural plate border and determine adjacent cell fates

PubMed Central

Woda, Juliana M.; Pastagia, Julie; Mercola, Mark; Artinger, Kristin Bruk

2014-01-01

Summary The lateral border of the neural plate is a major source of signals that induce primary neurons, neural crest cells and cranial placodes as well as provide patterning cues to mesodermal structures such as somites and heart. Whereas secreted BMP, FGF and Wnt proteins influence the differentiation of neural and non-neural ectoderm, we show here that members of the Dlx family of transcription factors position the border between neural and non-neural ectoderm and are required for the specification of adjacent cell fates. Inhibition of endogenous Dlx activity in Xenopus embryos with an EnR-Dlx homeodomain fusion protein expands the neural plate into non-neural ectoderm tissue whereas ectopic activation of Dlx target genes inhibits neural plate differentiation. Importantly, the stereotypic pattern of border cell fates in the adjacent ectoderm is re-established only under conditions where the expanded neural plate abuts Dlx-positive non-neural ectoderm. Experiments in which presumptive neural plate was grafted to ventral ectoderm reiterate induction of neural crest and placodal lineages and also demonstrate that Dlx activity is required in non-neural ectoderm for the production of signals needed for induction of these cells. We propose that Dlx proteins regulate intercellular signaling across the interface between neural and non-neural ectoderm that is critical for inducing and patterning adjacent cell fates. PMID:12466200

Wnt and FGF signals interact to coordinate growth with cell fate specification during limb development.

PubMed

ten Berge, Derk; Brugmann, Samantha A; Helms, Jill A; Nusse, Roel

2008-10-01

A fundamental question in developmental biology is how does an undifferentiated field of cells acquire spatial pattern and undergo coordinated differentiation? The development of the vertebrate limb is an important paradigm for understanding these processes. The skeletal and connective tissues of the developing limb all derive from a population of multipotent progenitor cells located in its distal tip. During limb outgrowth, these progenitors segregate into a chondrogenic lineage, located in the center of the limb bud, and soft connective tissue lineages located in its periphery. We report that the interplay of two families of signaling proteins, fibroblast growth factors (FGFs) and Wnts, coordinate the growth of the multipotent progenitor cells with their simultaneous segregation into these lineages. FGF and Wnt signals act together to synergistically promote proliferation while maintaining the cells in an undifferentiated, multipotent state, but act separately to determine cell lineage specification. Withdrawal of both signals results in cell cycle withdrawal and chondrogenic differentiation. Continued exposure to Wnt, however, maintains proliferation and re-specifies the cells towards the soft connective tissue lineages. We have identified target genes that are synergistically regulated by Wnts and FGFs, and show how these factors actively suppress differentiation and promote growth. Finally, we show how the spatial restriction of Wnt and FGF signals to the limb ectoderm, and to a specialized region of it, the apical ectodermal ridge, controls the distribution of cell behaviors within the growing limb, and guides the proper spatial organization of the differentiating tissues.

Modeling AEC—New Approaches to Study Rare Genetic Disorders

PubMed Central

Koch, Peter J.; Dinella, Jason; Fete, Mary; Siegfried, Elaine C.; Koster, Maranke I.

2015-01-01

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare monogenetic disorder that is characterized by severe abnormalities in ectoderm-derived tissues, such as skin and its appendages. A major cause of morbidity among affected infants is severe and chronic skin erosions. Currently, supportive care is the only available treatment option for AEC patients. Mutations in TP63, a gene that encodes key regulators of epidermal development, are the genetic cause of AEC. However, it is currently not clear how mutations in TP63 lead to the various defects seen in the patients’ skin. In this review, we will discuss current knowledge of the AEC disease mechanism obtained by studying patient tissue and genetically engineered mouse models designed to mimic aspects of the disorder. We will then focus on new approaches to model AEC, including the use of patient cells and stem cell technology to replicate the disease in a human tissue culture model. The latter approach will advance our understanding of the disease and will allow for the development of new in vitro systems to identify drugs for the treatment of skin erosions in AEC patients. Further, the use of stem cell technology, in particular induced pluripotent stem cells (iPSC), will enable researchers to develop new therapeutic approaches to treat the disease using the patient’s own cells (autologous keratinocyte transplantation) after correction of the disease-causing mutations. PMID:24665072

Molecular basis of hypohidrotic ectodermal dysplasia: an update.

PubMed

Trzeciak, Wieslaw H; Koczorowski, Ryszard

2016-02-01

Recent advances in understanding the molecular events underlying hypohidrotic ectodermal dysplasia (HED) caused by mutations of the genes encoding proteins of the tumor necrosis factor α (TNFα)-related signaling pathway have been presented. These proteins are involved in signal transduction from ectoderm to mesenchyme during development of the fetus and are indispensable for the differentiation of ectoderm-derived structures such as eccrine sweat glands, teeth, hair, skin, and/or nails. Novel data were reviewed and discussed on the structure and functions of the components of TNFα-related signaling pathway, the consequences of mutations of the genes encoding these proteins, and the prospect for further investigations, which might elucidate the origin of HED.

Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.

PubMed

Chaaya, Gerard; Morales, Jorge; Castiglioni, Analia; Subhani, Noman; Asmar, Abdo

2018-02-01

Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations. Published by Elsevier Inc.

Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation.

PubMed

Galve-Roperh, Ismael; Chiurchiù, Valerio; Díaz-Alonso, Javier; Bari, Monica; Guzmán, Manuel; Maccarrone, Mauro

2013-10-01

Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS). The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB1) and type-2 (CB2) cannabinoid receptors] and metabolic enzymes. Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved. Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm). In the ectoderm-derived nervous system, both CB1 and CB2 receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation. Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells. Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery. The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

The evolution of Msx gene function: expression and regulation of a sea urchin Msx class homeobox gene.

PubMed

Dobias, S L; Ma, L; Wu, H; Bell, J R; Maxson, R

1997-01-01

Msx- class homeobox genes, characterized by a distinct and highly conserved homeodomain, have been identified in a wide variety of metazoans from vertebrates to coelenterates. Although there is evidence that they participate in inductive tissue interactions that underlie vertebrate organogenesis, including those that pattern the neural crest, there is little information about their function in simple deuterostomes. Both to learn more about the ancient function of Msx genes, and to shed light on the evolution of developmental mechanisms within the lineage that gave rise to vertebrates, we have isolated and characterized Msx genes from ascidians and echinoderms. Here we describe the sequence and expression of a sea urchin (Strongylocentrotus purpouratus) Msx gene whose homeodomain is very similar to that of vertebrate Msx2. This gene, designated SpMsx, is first expressed in blastula stage embryos, apparently in a non-localized manner. Subsequently, during the early phases of gastrulation, SpMsx transcripts are expressed intensely in the invaginating archenteron and secondary mesenchyme, and at reduced levels in the ectoderm. In the latter part of gastrulation, SpMsx transcripts are concentrated in the oral ectoderm and gut, and continue to be expressed at those sites through the remainder of embryonic development. That vertebrate Msx genes are regulated by inductive tissue interactions and growth factors suggested to us that the restriction of SpMsx gene expression to the oral ectoderm and derivatives of the vegetal plate might similarly be regulated by the series of signaling events that pattern these embryonic territories. As a first test of this hypothesis, we examined the influence of exogastrulation and cell-dissociation on SpMsx gene expression. In experimentally-induced exogastrulae, SpMsx transcripts were distributed normally in the oral ectoderm, evaginated gut, and secondary mesenchyme. However, when embryos were dissociated into their component cells, SpMsx transcripts failed to accumulate. These data show that the localization of SpMsx transcripts in gastrulae does not depend on interactions between germ layers, yet the activation and maintenance of SpMsx expression does require cell-cell or cell-matrix interactions.

Prevalence of atopic disorders and immunodeficiency in patients with ectodermal dysplasia syndromes

PubMed Central

Mark, Barry J.; Becker, Bradley A.; Halloran, Donna R.; Bree, Alanna F.; Sindwani, Raj; Fete, Mary D.; Motil, Kathleen J.; Srun, Sopheak W.; Fete, Timothy J.

2013-01-01

Background Ectodermal dysplasia (ED) syndromes are a diverse group of disorders that affect multiple ectodermally derived tissues. Small studies and case reports suggest an increase in atopy and primary immunodeficiencies (PIDs) among patients with ED syndromes. Objective To determine the prevalence of clinical symptoms suggestive of atopy or immunodeficiency among a large cohort of children with ED syndromes. Methods A 9-page questionnaire was mailed to families who were members of the National Foundation for Ectodermal Dysplasias. The surveys were completed by parents of children younger than 18 years with a diagnosis of an ED syndrome or carrier state. Portions of the questionnaire were adapted from previously validated questionnaires developed by the International Study of Asthma and Allergies in Childhood (ISAAC). Results We received 347 completed questionnaires (41%). When compared with the 13- to 14-year-old children surveyed by ISAAC, we found both all-aged and age-matched children with ED syndromes, respectively, had significantly higher rates of asthma (32.2% and 37.2% vs 16.4%), rhinitis symptoms (76.1% and 78.3% vs 38.9%), and eczema (58.9% and 48.9% vs 8.2%). The prevalence of physician-diagnosed food allergies (20.7%) and PIDs (6.1%) in these ED patients also exceeded known rates in the general pediatric population. Conclusion This large-scale, retrospective study demonstrates a greater reported prevalence of symptoms suggestive of atopic disorders and PIDs among children with ED syndromes than the general pediatric population. A combination of genetic and environmental factors in ED syndromes may contribute to breaches of skin and mucosal barriers, permitting enhanced transmission and sensitization to irritants, allergens, and pathogens. PMID:22626597

Evolution of neural crest and placodes: amphioxus as a model for the ancestral vertebrate?

NASA Technical Reports Server (NTRS)

Holland, L. Z.; Holland, N. D.

2001-01-01

Recent studies of protochordates (ascidian tunicates and amphioxus) have given insights into possible ancestors of 2 of the characteristic features of the vertebrate head: neural crest and placodes. The neural crest probably evolved from cells on either side of the neural plate-epidermis boundary in a protochordate ancestral to the vertebrates. In amphioxus, homologues of several vertebrate neural crest marker genes (BMP2/4, Pax3/7, Msx, Dll and Snail) are expressed at the edges of the neural plate and/or adjacent nonneural ectoderm. Some of these markers are also similarly expressed in tunicates. In protochordates, however, these cells, unlike vertebrate neural crest, neither migrate as individuals through embryonic tissues nor differentiate into a wide spectrum of cell types. Therefore, while the protochordate ancestor of the vertebrates probably had the beginnings of a genetic programme for neural crest formation, this programme was augmented in the earliest vertebrates to attain definitive neural crest. Clear homologues of vertebrate placodes are lacking in protochordates. However, both amphioxus and tunicates have ectodermal sensory cells. In tunicates these are all primary neurons, sending axons to the central nervous system, while in amphioxus, the ectodermal sensory cells include both primary neurons and secondary neurons lacking axons. Comparisons of developmental gene expression suggest that the anterior ectoderm in amphioxus may be homologous to the vertebrate olfactory placode, the only vertebrate placode with primary, not secondary, neurons. Similarly, biochemical, morphological and gene expression data suggest that amphioxus and tunicates also have homologues of the adenohypophysis, one of the few vertebrate structures derived from nonneurogenic placodes. In contrast, the origin of the other vertebrate placodes is very uncertain.

Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos

NASA Technical Reports Server (NTRS)

Fredieu, J. R.; Cui, Y.; Maier, D.; Danilchik, M. V.; Christian, J. L.

1997-01-01

When Xenopus gastrulae are made to misexpress Xwnt-8, or are exposed to lithium ions, they develop with a loss of anterior structures. In the current study, we have characterized the neural defects produced by either Xwnt-8 or lithium and have examined potential cellular mechanisms underlying this anterior truncation. We find that the primary defect in embryos exposed to lithium at successively earlier stages during gastrulation is a progressive rostral to caudal deletion of the forebrain, while hindbrain and spinal regions of the CNS remain intact. Misexpression of Xwnt-8 during gastrulation produces an identical loss of forebrain. Our results demonstrate that lithium and Wnts can act upon either prospective neural ectodermal cells, or upon dorsal mesodermal cells, to cause a loss of anterior pattern. Specifically, ectodermal cells isolated from lithium- or Wnt-exposed embryos are unable to form anterior neural tissue in response to inductive signals from normal dorsal mesoderm. In addition, although dorsal mesodermal cells from lithium- or Wnt-exposed embryos are specified properly, and produce normal levels of the anterior neural inducing molecules noggin and chordin, they show a greatly reduced capacity to induce anterior neural tissue in conjugated ectoderm. Taken together, our results are consistent with a model in which Wnt- or lithium-mediated signals can induce either mesodermal or ectodermal cells to produce a dominant posteriorizing morphogen which respecifies anterior neural tissue as posterior.

Prosthodontic Management of Hypohidrotic Ectodermal Dysplasia with Anodontia: A Case Report in Pediatric Patient and Review of Literature

PubMed Central

Ladda, R; Gangadhar, SA; Kasat, VO; Bhandari, AJ

2013-01-01

Ectodermal dysplasias are rare hereditary disorders characterized by abnormal development of certain tissues and structures of ectodermal origin. The condition is important for dentists as it affects teeth resulting in hypodontia or anodontia and dentist plays an important role in rehabilitation of the patient. Affected young children with anodontia not only have difficulties in eating and speaking but can also feel that they look different from their contemporaries. Well-fitting and functioning prosthesis could be a great help during their schooling years as it will improve appearance and thus boost their self confidence. We report a case of hypohidrotic ectodermal dysplasia in an 8-year-old boy who exhibited anodontia and was successfully rehabilitated with conventional complete dentures in both maxillary and mandibular arches. The aim of the treatment was to improve psychological development apart from promoting better functioning of the stomatognathic system. PMID:23919206

In situ hybridization analysis of the temporospatial expression of the midkine/pleiotrophin family in rat embryonic pituitary gland.

PubMed

Fujiwara, Ken; Maliza, Rita; Tofrizal, Alimuddin; Batchuluun, Khongorzul; Ramadhani, Dini; Tsukada, Takehiro; Azuma, Morio; Horiguchi, Kotaro; Kikuchi, Motoshi; Yashiro, Takashi

2014-07-01

Pituitary gland development is controlled by numerous signaling molecules, which are produced in the oral ectoderm and diencephalon. A newly described family of heparin-binding growth factors, namely midkine (MK)/pleiotrophin (PTN), is involved in regulating the growth and differentiation of many tissues and organs. Using in situ hybridization with digoxigenin-labeled cRNA probes, we detected cells expressing MK and PTN in the developing rat pituitary gland. At embryonic day 12.5 (E12.5), MK expression was localized in Rathke's pouch (derived from the oral ectoderm) and in the neurohypophyseal bud (derived from the diencephalon). From E12.5 to E19.5, MK mRNA was expressed in the developing neurohypophysis, and expression gradually decreased in the developing adenohypophysis. To characterize MK-expressing cells, we performed double-staining of MK mRNA and anterior pituitary hormones. At E19.5, no MK-expressing cells were stained with any hormone. In contrast, PTN was expressed only in the neurohypophysis primordium during all embryonic stages. In situ hybridization clearly showed that MK was expressed in primitive (immature/undifferentiated) adenohypophyseal cells and neurohypophyseal cells, whereas PTN was expressed only in neurohypophyseal cells. Thus, MK and PTN might play roles as signaling molecules during pituitary development.

Topical cetirizine and oral vitamin D: a valid treatment for hypotrichosis caused by ectodermal dysplasia.

PubMed

Rossi, A; Miraglia, E; Fortuna, M C; Calvieri, S; Giustini, S

2017-02-01

Ectodermal dysplasia is a clinically and genetically heterogeneous group of inherited disorders characterized by abnormal development of two or more of the following ectodermal-derived structures: hair, teeth, nails and sweat glands. The hair is the most frequently affected structure. Hair shaft abnormalities are of great concern to these patients, but no effective treatments are available. We describe three girls with congenital hypotrichosis (9, 5 and 6 years old) caused by ectodermal dysplasia treated with topical cetirizine solution (2 mL. once daily) and oral vitamin D supplementation (1000 IU daily). After 6 months of treatment, the density of hair on the scalp increased in all patients. The vellus hair was replaced by terminal hair. Hair regrowth was evaluated both from the clinical and trichoscopic point of view. We propose a combination of topical cetirizine and oral vitamin D as a rational treatment of choice in congenital hypotrichosis caused by ectodermal dysplasia. © 2016 European Academy of Dermatology and Venereology.

Ectodermal Differentiation of Wharton's Jelly Mesenchymal Stem Cells for Tissue Engineering and Regenerative Medicine Applications.

PubMed

Jadalannagari, Sushma; Aljitawi, Omar S

2015-06-01

Mesenchymal stem cells (MSCs) from Wharton's jelly (WJ) of the human umbilical cord are perinatal stem cells that have self-renewal ability, extended proliferation potential, immunosuppressive properties, and are accordingly excellent candidates for tissue engineering. These MSCs are unique, easily accessible, and a noncontroversial cell source of regeneration in medicine. Wharton's jelly mesenchymal stem cells (WJMSCs) are multipotent and capable of multilineage differentiation into cells like adipocytes, bone, cartilage, and skeletal muscle upon exposure to appropriate conditions. The ectoderm is one of the three primary germ layers found in the very early embryo that differentiates into the epidermis, nervous system (spine, peripheral nerves, brain), and exocrine glands (mammary, sweat, salivary, and lacrimal glands). Accumulating evidence shows that MSCs obtained from WJ have an ectodermal differentiation potential. The current review examines this differentiation potential of WJMSC into the hair follicle, skin, neurons, and sweat glands along with discussing the potential utilization of such differentiation in regenerative medicine.

Keratoprosthesis in Ectodermal Dysplasia.

PubMed

Wozniak, Rachel A F; Gonzalez, Mithra; Aquavella, James V

2016-07-01

To describe the complex surgical management and novel medical approach for a keratoprosthesis (KPro Boston type I) in a monocular, 73-year-old patient with ectodermal dysplasia and chronic, noninfectious corneal necrosis. Best-corrected visual acuity (BCVA) was measured with Snellen letters. Surgical intervention included an amniotic membrane graft, complete replacement of the KPro, conjunctival flap graft, corneal donor tissue grafts combined with inferior rectus muscle advancement, periosteal tissue graft, tarso-conjunctival flap construction, and symblepharolysis. Infliximab was used as a medical adjunctive therapy. Initial KPro placement provided a BCVA of 20/25 and long-term stability. Subsequent chronic melting at the optic border necessitated numerous surgeries to prevent extrusion and failure. Ultimate fistulization was addressed with the formation of a surgical pocket. The addition of infliximab promoted ocular surface stability, and the patient has maintained a BCVA of 20/80. Ectodermal dysplasia can result in eyelid and corneal abnormalities, requiring a KPro for visual restoration. In the setting of chronic, sterile corneal melt, novel surgical approaches and the off-label use of infliximab allowed for visual rehabilitation.

Bilateral congenital lacrimal fistulas in an adult as part of ectrodactyly-ectodermal dysplasia-clefting syndrome: A rare anomaly.

PubMed

Ghosh, Debangshu; Saha, Somnath; Basu, Sumit Kumar

2015-10-01

Ectrodactyly-ectodermal dysplasia and clefting syndrome or "Lobster claw" deformity is a rare congenital anomaly that affects tissues of ectodermal and mesodermal origin. Nasolacrimal duct (NLD) obstruction with or without atresia of lacrimal passage is a common finding of such a syndrome. The authors report here even a rarer presentation of the syndrome which manifested as bilateral NLD obstruction and lacrimal fistula along with cleft lip and palate, syndactyly affecting all four limbs, mild mental retardation, otitis media, and sinusitis. Lacrimal duct obstruction and fistula were managed successfully with endoscopic dacryocystorhinostomy (DCR) which is a good alternative to lacrimal probing or open DCR in such a case.

Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome.

PubMed

Rachmiel, Adi; Turgeman, Shahar; Emodi, Omri; Aizenbud, Dror; Shilo, Dekel

2018-02-01

Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation.

Management of Severely Atrophic Maxilla in Ectrodactyly Ectodermal Dysplasia-cleft Syndrome

PubMed Central

Rachmiel, Adi; Emodi, Omri; Aizenbud, Dror; Shilo, Dekel

2018-01-01

Background: Ectrodactyly ectodermal dysplasia-cleft syndrome is a rare genetic syndrome with an incidence of 1/90,000 live births, characterized by cleft lip and palate, severely hypoplastic maxilla, and hypodontia. Patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome suffer from a severely hypoplastic maxilla that is highly difficult to treat using traditional orthognathic methods. In this study, we propose using distraction osteogenesis to achieve a major advancement while maintaining good stability and minimal relapse. To our knowledge, this is the first description of patients with this syndrome treated using distraction osteogenesis. Methods: Five patients diagnosed with ectrodactyly ectodermal dysplasia-cleft syndrome were included in the study. All patients had been operated on according to the well-established protocol of cleft lip and palate reconstruction before maxillary distraction osteogenesis. Hard and soft-tissue changes were evaluated by cone beam computed tomography and lateral cephalograms before distraction osteogenesis (T1), at the postdistraction point (T2) and after 1 year of follow-up (T3). Results: Examination revealed marked maxillary advancement in all our patients with a significant mean difference in hard tissue parameters (condylion to A point = 18 mm; nasion-sella line to A point = 15.2 degrees) and a notable improvement in facial convexity (20.9 degrees). One year follow-up measurements demonstrated mild relapse rates of 6% in the horizontal plane. Conclusions: We conclude that despite the challenging anatomic and physiological features of ectrodactyly ectodermal dysplasia-cleft patients, by enhancing current surgical techniques, there is promising potential for improved patient outcomes, achieving normognathic facial appearance with implant supported rehabilitation. PMID:29616174

Tissue interactions in the induction of anterior pituitary: role of the ventral diencephalon, mesenchyme, and notochord.

PubMed

Gleiberman, A S; Fedtsova, N G; Rosenfeld, M G

1999-09-15

Rathke's pouch, the epithelial primordium of the anterior pituitary, differentiates in close topographical and functional association with the ventral diencephalon. It is still not known whether the ventral diencephalon acts as the initial inducer of pituitary development. The roles of the adjacent mesenchyme and notochord, two other tissues located in close proximity to Rathke's pouch, in this process are even less clear. In this report we describe an in vitro experimental system that reproduces the earliest steps of anterior pituitary development. We provide evidence that the ventral diencephalon from 2- to 4-day-old chick embryos is able to function as an inducer of pituitary development and can convert early chick embryonic head ectoderm, which is not involved normally in pituitary development, into typical anterior pituitary tissue. This induction is contact-dependent. In our experimental system, there is a requirement for the supporting action of mesenchyme, which is independent of the mesenchyme source. Transplantation of the notochord into the lateral head region of a six-somite chick embryo induces an epithelial invagination, suggesting that the notochord induces the outpouching of the roof of the stomodeal ectoderm that results in formation of Rathke's pouch and causes the close contact between this ectoderm and the ventral diencephalon. Finally, we demonstrate that the ventral diencephalon from e9.5-e11.5 mouse embryos is also an efficient inducer of anterior pituitary differentiation in chick embryonic lateral head ectoderm, suggesting that the mechanism of anterior pituitary induction is conserved between mammals and birds, using the same, or similar, signaling pathways. Copyright 1999 Academic Press.

Constitutively Active Akt Induces Ectodermal Defects and Impaired Bone Morphogenetic Protein Signaling

PubMed Central

Segrelles, Carmen; Moral, Marta; Lorz, Corina; Santos, Mirentxu; Lu, Jerry; Cascallana, José Luis; Lara, M. Fernanda; Carbajal, Steve; Martínez-Cruz, Ana Belén; García-Escudero, Ramón; Beltran, Linda; Segovia, José C.; Bravo, Ana

2008-01-01

Aberrant activation of the Akt pathway has been implicated in several human pathologies including cancer. However, current knowledge on the involvement of Akt signaling in development is limited. Previous data have suggested that Akt-mediated signaling may be an essential mediator of epidermal homeostasis through cell autonomous and noncell autonomous mechanisms. Here we report the developmental consequences of deregulated Akt activity in the basal layer of stratified epithelia, mediated by the expression of a constitutively active Akt1 (myrAkt) in transgenic mice. Contrary to mice overexpressing wild-type Akt1 (Aktwt), these myrAkt mice display, in a dose-dependent manner, altered development of ectodermally derived organs such as hair, teeth, nails, and epidermal glands. To identify the possible molecular mechanisms underlying these alterations, gene profiling approaches were used. We demonstrate that constitutive Akt activity disturbs the bone morphogenetic protein-dependent signaling pathway. In addition, these mice also display alterations in adult epidermal stem cells. Collectively, we show that epithelial tissue development and homeostasis is dependent on proper regulation of Akt expression and activity. PMID:17959825

Engineering epithelial-stromal interactions in vitro for toxicology assessment.

PubMed

Belair, David G; Abbott, Barbara D

2017-05-01

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues. Published by Elsevier B.V.

Engineering epithelial-stromal interactions in vitro for toxicology assessment

PubMed Central

Belair, David G.; Abbott, Barbara D.

2018-01-01

Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue homeostasis. Epithelial-stromal interactions (ESIs) have historically been examined using mammalian models and ex vivo tissue recombination. Although these approaches have elucidated signaling mechanisms underlying embryonic morphogenesis processes and adult mammalian epithelial tissue function, they are limited by the availability of tissue, low throughput, and human developmental or physiological relevance. In this review, we describe how bioengineered ESIs, using either human stem cells or co-cultures of human primary epithelial and stromal cells, have enabled the development of human in vitro epithelial tissue models that recapitulate the architecture, phenotype, and function of adult human epithelial tissues. We discuss how the strategies used to engineer mature epithelial tissue models in vitro could be extrapolated to instruct the design of organotypic culture models that can recapitulate the structure of embryonic ectodermal tissues and enable the in vitro assessment of events critical to organ/tissue morphogenesis. Given the importance of ESIs towards normal epithelial tissue development and function, such models present a unique opportunity for toxicological screening assays to incorporate ESIs to assess the impact of chemicals on mature and developing epidermal tissues. PMID:28285100

Ear nose throat manifestations in hypoidrotic ectodermal dysplasia.

PubMed

Callea, Michele; Teggi, Roberto; Yavuz, Izzet; Tadini, Gianluca; Priolo, Manuela; Crovella, Sergio; Clarich, Gabriella; Grasso, Domenico Leonardo

2013-11-01

The ectodermal dysplasias (EDs) are a large and complex group of inherited disorders. In various combinations, they all share anomalies in ectodermal derived structures: hair, teeth, nails and sweat gland function. Clinical overlap is present among EDs. Few causative genes have been identified, to date. Altered gene expression is not limited to the ectoderm but a concomitant effect on developing mesenchymal structures, with modification of ectodermal-mesenchymal signaling, takes place. The two major categories of ED include the hidrotic and hypohidrotic form, the latter more frequent; they differentiate each other for the presence or absence of sweat glands. We report Ear Nose Throat manifestations of ED, linked to the reduction of mucous glands in the nasal fossae with reduced ciliar function, and decrease salivary glands function. Often patients report an increased rate of infections of the upper respiratory tract and of the ear. Nasal obstruction due to the presence of nasal crusting, hearing loss and throat hoarseness are the most represented symptoms. Environmental measures, including a correct air temperature and humidification, is mandatory above all in subjects affected by hypohidrotic form. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Molecular-clinical correlation in a family with a novel heteroplasmic Leigh syndrome missense mutation in the mitochondrial cytochrome c oxidase III gene.

PubMed

Mkaouar-Rebai, Emna; Ellouze, Emna; Chamkha, Imen; Kammoun, Fatma; Triki, Chahnez; Fakhfakh, Faiza

2011-01-01

Cytochrome c oxidase is an essential component of the mitochondrial respiratory chain that catalyzes the reduction of molecular oxygen by reduced cytochrome c. In this study, the authors report the second mutation associated with Leigh syndrome in the blood and buccal mucosa of 2 affected members of a Tunisian family. It was a novel heteroplasmic missense mitochondrial mutation at nucleotide 9478 in the gene specifying subunit III of cytochrome c oxidase substituting the valine at position 91 to alanine in a highly conserved amino acid. It was found with a high mutant load in tissues derived from endoderm (buccal mucosa) and mesoderm (blood). However, it was nearly absent in tissue derived from ectoderm (hair follicles). It was absent in 120 healthy controls, and PolyPhen analysis showed that the hydropathy index changed from +1.276 to +0.242, and the number of structures of the 3D protein decreased from 39 to 32.

Dermatopathia pigmentosa reticularis: A rare reticulate pigmentary disorder

PubMed Central

Shanker, Vinay; Gupta, Mudita

2013-01-01

Dermatopathia pigmentosa reticularis is a rare ectodermal dysplasia with a triad of generalized reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. We report a case of a 21 year old woman who had generalized reticulate pigmentation, diffuse noncicatricial alopecia and onychodystrophy of finger and toe nails. Along with this triad she had palmoplantar keratoderma and poorly developed dermatoglyphics. There was no evidence of involvement of other ectodermally derived organ. PMID:23440032

The canonical Wnt signaling activator, R-spondin2, regulates craniofacial patterning and morphogenesis within the branchial arch through ectodermal-mesenchymal interaction

PubMed Central

Jin, Yong-Ri; Turcotte, Taryn J.; Crocker, Alison L.; Han, Xiang Hua; Yoon, Jeong Kyo

2011-01-01

R-spondins are a recently characterized family of secreted proteins that activate Wnt/β-catenin signaling. Herein, we determine R-spondin2 (Rspo2) function in craniofacial development in mice. Mice lacking a functional Rspo2 gene exhibit craniofacial abnormalities such as mandibular hypoplasia, maxillary and mandibular skeletal deformation, and cleft palate. We found that loss of the mouse Rspo2 gene significantly disrupted Wnt/β-catenin signaling and gene expression within the first branchial arch (BA1). Rspo2, which is normally expressed in BA1 mesenchymal cells, regulates gene expression through a unique ectoderm-mesenchyme interaction loop. The Rspo2 protein, potentially in combination with ectoderm-derived Wnt ligands, up-regulates Msx1 and Msx2 expression within mesenchymal cells. In contrast, Rspo2 regulates expression of the Dlx5, Dlx6, and Hand2 genes in mesenchymal cells via inducing expression of their upstream activator, Endothelin1 (Edn1), within ectodermal cells. Loss of Rspo2 also causes increased cell apoptosis, especially within the aboral (or caudal) domain of the BA1, resulting in hypoplasia of the BA1. Severely reduced expression of Fgf8, a survival factor for mesenchymal cells, in the ectoderm of Rspo2−/− embryos is likely responsible for increased cell apoptosis. Additionally, we found that cleft palate in Rspo2−/− mice is not associated with defects intrinsic to the palatal shelves. A possible cause of cleft palate is a delay of proper palatal shelf elevation that may result from the small mandible and a failure of lowering the tongue. Thus, our study identifies Rspo2 as a mesenchyme-derived factor that plays critical roles in regulating BA1 patterning and morphogenesis through ectodermal-mesenchymal interaction and a novel genetic factor for cleft palate. PMID:21237142

Engineering the extracellular matrix for clinical applications: endoderm, mesoderm, and ectoderm.

PubMed

Williams, Miguel L; Bhatia, Sujata K

2014-03-01

Tissue engineering is rapidly progressing from a research-based discipline to clinical applications. Emerging technologies could be utilized to develop therapeutics for a wide range of diseases, but many are contingent on a cell scaffold that can produce proper tissue ultrastructure. The extracellular matrix, which a cell scaffold simulates, is not merely a foundation for tissue growth but a dynamic participant in cellular crosstalk and organ homeostasis. Cells change their growth rates, recruitment, and differentiation in response to the composition, modulus, and patterning of the substrate on which they reside. Cell scaffolds can regulate these factors through precision design, functionalization, and application. The ideal therapy would utilize highly specialized cell scaffolds to best mimic the tissue of interest. This paper discusses advantages and challenges of optimized cell scaffold design in the endoderm, mesoderm, and ectoderm for clinical applications in tracheal transplant, cardiac regeneration, and skin grafts, respectively. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiphasic and tissue-specific roles of sonic hedgehog in cloacal septation and external genitalia development

PubMed Central

Seifert, Ashley W.; Bouldin, Cortney M.; Choi, Kyung-Suk; Harfe, Brian D.; Cohn, Martin J.

2009-01-01

Malformations of the external genitalia are among the most common congenital anomalies in humans. The urogenital and anorectal sinuses develop from the embryonic cloaca, and the penis and clitoris develop from the genital tubercle. Within the genital tubercle, the endodermally derived urethral epithelium functions as an organizer and expresses sonic hedgehog (Shh). Shh knockout mice lack external genitalia and have a persistent cloaca. This identified an early requirement for Shh, but precluded analysis of its later role in the genital tubercle. We conducted temporally controlled deletions of Shh and report that Shh is required continuously through the onset of sexual differentiation. Shh function is divisible into two temporal phases; an anogenital phase, during which Shh regulates outgrowth and patterning of the genital tubercle and septation of the cloaca, and a later external genital phase, during which Shh regulates urethral tube closure. Disruption of Shh function during the anogenital phase causes coordinated anorectal and genitourinary malformations, whereas inactivation during the external genital phase causes hypospadias. Shh directs cloacal septation by promoting cell proliferation in adjacent urorectal septum mesenchyme. Additionally, conditional inactivation of smoothened in the genital ectoderm and cloacal/urethral endoderm shows that the ectoderm is a direct target of Shh and is required for urethral tube closure, highlighting a novel role for genital ectoderm in urethragenesis. Identification of the stages during which disruption of Shh results in either isolated or coordinated malformations of anorectal and external genital organs provides a new tool for investigating the etiology of anogenital malformations in humans. PMID:19906862

An unusual case of ectodermal dysplasia: combating senile features at an early age

PubMed Central

Gupta, Mudit; Sundaresh, Kumbar Jayadevappa; Batra, Manu; Rathva, Vandana J

2014-01-01

Ectodermal dysplasia (ED) refers to a group of inherited diseases that have developmental defects in at least two major structures derived from the ectoderm, that is, hair, teeth, nails and sweat glands. Although more than 192 distinct disorders have been described, the most common is X-linked recessive hypohidrotic ED (Christ-Siemens-Touraine syndrome). Since such patients usually presents with missing teeth, dentists are usually the first person to diagnose such cases. Diagnosis of such cases is important because absence of sweat glands can lead to hyperthermia which can be life-threatening if proper care is not taken. Through this manuscript, we report a case of anhidrotic ED affecting deciduous and permanent dentition, which is rare. PMID:24493109

A Novel Splicesite Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohydrotic (Anhidrotic) Ectodermal Dysplasia in an Iranian Family.

PubMed

Torkamandi, Shahram; Gholami, Milad; Mohammadi-Asl, Javad; Rezaie, Somaye; Zaimy, Mohammad Ali; Omrani, Mir Davood

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare congenital disorder arising from deficient development of ectoderm-derived structures including skin, nails, glands and teeth. The phenotype of HED is associated with mutation in EDA, EDAR, EDARADD and NEMO genes, all of them disruptingNF-κB signaling cascade necessary for initiation, formation and differentiation in the embryo and adult. Here we describe a novel acceptor splice site mutation c.730-2 A>G(IVS 8-2 A>G) in EDAR gene in homozygous form in all affected members of a family,and in heterozygous form in carriers. Bioinformatics analysis showed that this mutation can create a new broken splicing site and lead to aberrant splicing.

Conventional Complete Denture in Patients with Ectodermal Dysplasia

PubMed Central

Vilanova, Larissa Soares Reis; Sánchez-Ayala, Alfonso; Ribeiro, Giselle Rodrigues; Campos, Camila Heitor; Farias-Neto, Arcelino

2015-01-01

Ectodermal dysplasia is described as heritable conditions that involve anomalies of structures derived from the ectoderm, including hypodontia. In the cases of edentulous young patients, who did not finish their craniofacial growth, treatment with conventional complete denture is a suitable alternative. The aim of this study was to report a case of mandibular edentulism treated with conventional complete denture in a thirteen-year-old patient diagnosed with hidrotic ectodermal dysplasia. Typical features, such as frontal bossing, depressed nasal bridge, protuberant lips, scarce hair, and brittle nails, were visualized during the extraoral examination. The intraoral inspection and radiographic analysis revealed oligodontia, dental malformation, and prolonged retention of deciduous teeth at maxilla and total edentulism at mandible. A conventional complete denture was planned and constructed following the same steps of technique as recommended in adults. Although this option is not a definitive treatment, the patient and his parents were satisfied with his improvement in chewing and speech, as well as with the aesthetic benefits. PMID:26425372

A Novel Splicesite Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohydrotic (Anhidrotic) Ectodermal Dysplasia in an Iranian Family

PubMed Central

Torkamandi, Shahram; Gholami, Milad; Mohammadi-asl, Javad; Rezaie, Somaye; Zaimy, Mohammad Ali; Omrani, Mir Davood

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare congenital disorder arising from deficient development of ectoderm-derived structures including skin, nails, glands and teeth. The phenotype of HED is associated with mutation in EDA, EDAR, EDARADD and NEMO genes, all of them disruptingNF-κB signaling cascade necessary for initiation, formation and differentiation in the embryo and adult. Here we describe a novel acceptor splice site mutation c.730-2 A>G(IVS 8-2 A>G) in EDAR gene in homozygous form in all affected members of a family,and in heterozygous form in carriers. Bioinformatics analysis showed that this mutation can create a new broken splicing site and lead to aberrant splicing. PMID:28357203

Using implants for prosthodontic rehabilitation of a 4-year-old with ectodermal dysplasia.

PubMed

Toomarian, Lida; Ardakani, Mohammad Reza Talebi; Ramezani, Jamileh; Adli, Amin Rezaei; Tabari, Zahra Alizadeh

2014-01-01

Ectodermal dysplasia (ED) is an inherited disorder that affects ectodermally derived organs, such as teeth. Pathogenesis is thought to involve an altered epithelium-mesenchymal interaction. ED patients have oligodontia (or sometimes anodontia) in addition to other abnormalities involving the skin, sweat glands, or hair. Many different subtypes have been introduced in the literature. This article describes the case of a 4-year-old patient who, after being diagnosed with ED, was put on a treatment plan that involved mandibular implants, reshaping of the maxillary primary central incisors, and prosthetic dental rehabilitation. Due to the child's rapid growth, both dentures were changed 9 months post-treatment. Two years post-treatment, the maxillary denture was changed again and the child was placed under close supervision.

Impaired epithelial differentiation of induced pluripotent stem cells from ectodermal dysplasia-related patients is rescued by the small compound APR-246/PRIMA-1MET.

PubMed

Shalom-Feuerstein, Ruby; Serror, Laura; Aberdam, Edith; Müller, Franz-Josef; van Bokhoven, Hans; Wiman, Klas G; Zhou, Huiqing; Aberdam, Daniel; Petit, Isabelle

2013-02-05

Ectodermal dysplasia is a group of congenital syndromes affecting a variety of ectodermal derivatives. Among them, ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome is caused by single point mutations in the p63 gene, which controls epidermal development and homeostasis. Phenotypic defects of the EEC syndrome include skin defects and limbal stem-cell deficiency. In this study, we designed a unique cellular model that recapitulated major embryonic defects related to EEC. Fibroblasts from healthy donors and EEC patients carrying two different point mutations in the DNA binding domain of p63 were reprogrammed into induced pluripotent stem cell (iPSC) lines. EEC-iPSC from both patients showed early ectodermal commitment into K18(+) cells but failed to further differentiate into K14(+) cells (epidermis/limbus) or K3/K12(+) cells (corneal epithelium). APR-246 (PRIMA-1(MET)), a small compound that restores functionality of mutant p53 in human tumor cells, could revert corneal epithelial lineage commitment and reinstate a normal p63-related signaling pathway. This study illustrates the relevance of iPSC for p63 related disorders and paves the way for future therapy of EEC.

Ophthalmic manifestations in patients with ectodermal dysplasia syndromes.

PubMed

Keklikci, Ugur; Yavuz, Izzet; Tunik, Selcuk; Ulku, Zelal Baskan; Akdeniz, Sedat

2014-01-01

Ectodermal dysplasia (ED) is a disorder that results from abnormal formation of at least two of the four major ectodermal derivatives in the developing embryo. The ectoderm of the embryo forms the skin, teeth, hair and nails, sweat glands and part of the eyes. The aim of this article is to reveal ophthalmologic symptoms and signs as multidisciplinary, reliable criteria for ectodermal dysplasia. In this retrospective study, 24 patients with ED were analyzed from the recorded data. Ophthalmological examination of the patients, who had previously received the diagnosis of ED in the dental department, was done. During the examination, ocular symptoms related to tear film, corneal changes, lacrimal duct, periorbital hyperpigmentation, alteration lashes and eyebrows were evaluated. The age ranged between 3-45, and the mean and standard deviation (Mean ± SD) was 15.8 ± 7.4 years. The number of males was 13 (54.2%) and females, 11 (45.8%). Eighteen patients (75.0%) suffered from ocular complaints related to the ocular surface. In 11 of the patients with ED, there were dry eye symptoms. While the mean age of cases with eye involvement was 17.5, it was 23.1 in cases with dry eye symptoms. In the study, it was observed that, in patients with ED, ocular complaints, particularly dry eye symptoms, may increase as age advances.

Frontal dermoid cyst coexisting with suprasellar craniopharyngioma: a spectrum of ectodermally derived epithelial-lined cystic lesions?

PubMed

Abou-Al-Shaar, Hussam; Abd-El-Barr, Muhammad M; Zaidi, Hasan A; Russell-Goldman, Eleanor; Folkerth, Rebecca D; Laws, Edward R; Chiocca, E Antonio

2016-12-01

There is a wide group of lesions that may exist in the sellar and suprasellar regions. Embryologically, there is varying evidence that many of these entities may in fact represent a continuum of pathology deriving from a common ectodermal origin. The authors report a case of a concomitant suprasellar craniopharyngioma invading the third ventricle with a concurrent frontal lobe cystic dermoid tumor. A 21-year-old man presented to the authors' service with a 3-day history of worsening headache, nausea, vomiting, and blurry vision. Magnetic resonance imaging depicted a right frontal lobe lesion associated with a separate suprasellar cystic lesion invading the third ventricle. The patient underwent a right pterional craniotomy for resection of both lesions. Gross-total resection of the right frontal lesion was achieved, and subtotal resection of the suprasellar lesion was accomplished with some residual tumor adherent to the walls of the third ventricle. Histopathological examination of the resected right frontal lesion documented a diagnosis of dermoid cyst and, for the suprasellar lesion, a diagnosis of adamantinomatous craniopharyngioma. The occurrence of craniopharyngioma with dermoid cyst has not been reported in the literature before. Such an association might indeed suggest the previously reported hypothesis that these lesions represent a spectrum of ectodermally derived epithelial-lined cystic lesions.

Genipin-crosslinked gelatin-silk fibroin hydrogels for modulating the behaviour of pluripotent cells.

PubMed

Sun, Wei; Incitti, Tania; Migliaresi, Claudio; Quattrone, Alessandro; Casarosa, Simona; Motta, Antonella

2016-10-01

Different hydrogel materials have been prepared to investigate the effects of culture substrate on the behaviour of pluripotent cells. In particular, genipin-crosslinked gelatin-silk fibroin hydrogels of different compositions have been prepared, physically characterized and used as substrates for the culture of pluripotent cells. Pluripotent cells cultured on hydrogels remained viable and proliferated. Gelatin and silk fibroin promoted the proliferation of cells in the short and long term, respectively. Moreover, cells cultured on genipin-crosslinked gelatin-silk fibroin blended hydrogels were induced to an epithelial ectodermal differentiation fate, instead of the neural ectodermal fate obtained by culturing on tissue culture plates. This work confirms that specific culture substrates can be used to modulate the behaviour of pluripotent cells and that our genipin-crosslinked gelatin-silk fibroin blended hydrogels can induce pluripotent cells differentiation to an epithelial ectodermal fate. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

The role of Foxi family transcription factors in otic placode and neural crest cell development

PubMed Central

Edlund, Renée K.; Birol, Onur; Groves, Andrew K.

2015-01-01

The mammalian outer, middle and inner ears have different embryonic origins and evolved at different times in the vertebrate lineage. The outer ear is derived from first and second branchial arch ectoderm and mesoderm, the middle ear ossicles are derived from neural crest mesenchymal cells that invade the first and second branchial arches, whereas the inner ear and its associated vestibule-acoustic (VIIIth) ganglion are derived from the otic placode. In this review, we discuss recent findings in the development of these structures and describe the contributions of members of a Forkhead transcription factor family, the Foxi family to their formation. Foxi transcription factors are critical for formation of the otic placode, survival of the branchial arch neural crest, and developmental remodeling of the branchial arch ectoderm. PMID:25662269

Heterotopic salivary gland tissue: a case report demonstrating evolution and association with the branchial apparatus.

PubMed

Chang, Wen-Yu; Lee, Ka-Wo; Tsai, Kun-Bow; Chen, Gwo-Shing

2005-09-01

Heterotopic salivary gland tissue (HSGT) in the lower neck is an unusual developmental anomaly with characteristic clinical and microscopic findings. The exact embryogenesis remains unclear. This rare entity must be considered in the differential diagnosis of neck mass with fistula. We present a typical HSGT totally removed using the stepladder excision technique and showing an internal fistula. Interpretation of this case from the anatomical and pathological points of view, we support the argument that the embryogenesis of HSGT is more probably related to ectodermal heteroplasia of the precervical sinus of His and further conclude that an association with branchial cleft sinus may exist and cannot be seen as an exclusion criteria for diagnosis of HSGT. Due to possible but infrequent neoplastic transformation, it is important to check HSGT in every encountered cervical anomaly related to any branchial apparatus derived lesion.

Potential skin involvement in ALS: revisiting Charcot's observation - a review of skin abnormalities in ALS.

PubMed

Paré, Bastien; Gros-Louis, François

2017-07-26

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients' skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novel in vitro ALS tissue-engineered skin model, derived from patients, for the study of ALS.

Specification of functional cranial placode derivatives from human pluripotent stem cells.

PubMed

Dincer, Zehra; Piao, Jinghua; Niu, Lei; Ganat, Yosif; Kriks, Sonja; Zimmer, Bastian; Shi, Song-Hai; Tabar, Viviane; Studer, Lorenz

2013-12-12

Cranial placodes are embryonic structures essential for sensory and endocrine organ development. Human placode development has remained largely inaccessible despite the serious medical conditions caused by the dysfunction of placode-derived tissues. Here, we demonstrate the efficient derivation of cranial placodes from human pluripotent stem cells. Timed removal of the BMP inhibitor Noggin, a component of the dual-SMAD inhibition strategy of neural induction, triggers placode induction at the expense of CNS fates. Concomitant inhibition of fibroblast growth factor signaling disrupts placode derivation and induces surface ectoderm. Further fate specification at the preplacode stage enables the selective generation of placode-derived trigeminal ganglia capable of in vivo engraftment, mature lens fibers, and anterior pituitary hormone-producing cells that upon transplantation produce human growth hormone and adrenocorticotropic hormone in vivo. Our results establish a powerful experimental platform to study human cranial placode development and set the stage for the development of human cell-based therapies in sensory and endocrine disease. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Oral Rehabilitation of a Patient With Ectodermal Dysplasia Treated With Fresh-Frozen Bone Allografts and Computer-Guided Implant Placement: A Clinical Case Report.

PubMed

Maiorana, Carlo; Poli, Pier Paolo; Poggio, Carlo; Barbieri, Paola; Beretta, Mario

2017-05-01

Ectodermal dysplasia (ED) is an inherited disorder characterized by abnormality of ectodermally derived structures. A recurrent oral finding is oligodontia, which in turn leads to a severely hypotrophic alveolar process with typical knife-edge morphology and adverse ridge contours. This unfavorable anatomy can seriously hamper proper implant placement. Fresh-frozen bone (FFB) allografts recently have been proposed to augment the residual bone volume for implant placement purposes; however, scientific evidence concerning the use of FFB to treat ED patients is absent. Similarly, data reporting computer-aided template-guided implant placement in medically compromised patients are limited. Thus the purpose of this report is to illustrate the oral rehabilitation of a female patient affected by ED and treated with appositional FFB block grafts and consecutive computer-guided flapless implant placement in a 2-stage procedure. Fixed implant-supported dental prostheses were finally delivered to the patient, which improved her self-esteem and quality of life. During the follow-up recall 1 year after the prosthetic loading, the clinical examination showed healthy peri-implant soft tissues with no signs of bleeding on probing or pathologic probing depths. The panoramic radiograph confirmed the clinical stability of the result. Peri-implant marginal bone levels were radiographically stable with neither pathologic bone loss at the mesial and distal aspects of each implant nor peri-implant radiolucency. Within the limitations of this report, the use of FFB allografts in association with computer-aided flapless implant surgery might be considered a useful technique in patients affected by ED. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Catalase characterization and implication in bleaching of a symbiotic sea anemone.

PubMed

Merle, Pierre-Laurent; Sabourault, Cécile; Richier, Sophie; Allemand, Denis; Furla, Paola

2007-01-15

Symbiotic cnidarians are marine invertebrates harboring photosynthesizing microalgae (named zooxanthellae), which produce great amounts of oxygen and free radicals upon illumination. Studying antioxidative balance is then crucial to understanding how symbiotic cnidarians cope with ROS production. In particular, it is suspected that oxidative stress triggers cnidarian bleaching, i.e., the expulsion of zooxanthellae from the animal host, responsible for symbiotic cnidarian mass mortality worldwide. This study therefore investigates catalase antioxidant enzymes and their role in bleaching of the temperate symbiotic sea anemone Anemonia viridis. Using specific separation of animal tissues (ectoderm and endoderm) from the symbionts (zooxanthellae), spectrophotometric assays and native PAGE revealed both tissue-specific and activity pattern distribution of two catalase electrophoretypes, E1 and E2. E1, expressed in all three tissues, presents high sensitivity to the catalase inhibitor aminotriazole (ATZ) and elevated temperatures. The ectodermal E1 form is responsible for 67% of total catalase activity. The E2 form, expressed only within zooxanthellae and their host endodermal cells, displays low sensitivity to ATZ and relative thermostability. We further cloned an ectodermal catalase, which shares 68% identity with mammalian monofunctional catalases. Last, 6 days of exposure of whole sea anemones to ATZ (0.5 mM) led to effective catalase inhibition and initiated symbiont expulsion. This demonstrates the crucial role of this enzyme in cnidarian bleaching, a phenomenon responsible for worldwide climate-change-induced mass mortalities, with catastrophic consequences for marine biodiversity.

Development and evolution of the vertebrate primary mouth

PubMed Central

Soukup, Vladimír; Horácek, Ivan; Cerny, Robert

2013-01-01

The vertebrate oral region represents a key interface between outer and inner environments, and its structural and functional design is among the limiting factors for survival of its owners. Both formation of the respective oral opening (primary mouth) and establishment of the food-processing apparatus (secondary mouth) require interplay between several embryonic tissues and complex embryonic rearrangements. Although many aspects of the secondary mouth formation, including development of the jaws, teeth or taste buds, are known in considerable detail, general knowledge about primary mouth formation is regrettably low. In this paper, primary mouth formation is reviewed from a comparative point of view in order to reveal its underestimated morphogenetic diversity among, and also within, particular vertebrate clades. In general, three main developmental modes were identified. The most common is characterized by primary mouth formation via a deeply invaginated ectodermal stomodeum and subsequent rupture of the bilaminar oral membrane. However, in salamander, lungfish and also in some frog species, the mouth develops alternatively via stomodeal collar formation contributed both by the ecto- and endoderm. In ray-finned fishes, on the other hand, the mouth forms via an ectoderm wedge and later horizontal detachment of the initially compressed oral epithelia with probably a mixed germ-layer derivation. A very intriguing situation can be seen in agnathan fishes: whereas lampreys develop their primary mouth in a manner similar to the most common gnathostome pattern, hagfishes seem to undergo a unique oropharyngeal morphogenesis when compared with other vertebrates. In discussing the early formative embryonic correlates of primary mouth formation likely to be responsible for evolutionary–developmental modifications of this area, we stress an essential role of four factors: first, positioning and amount of yolk tissue; closely related to, second, endoderm formation during gastrulation, which initiates the process and constrains possible evolutionary changes within this area; third, incipient structure of the stomodeal primordium at the anterior neural plate border, where the ectoderm component of the prospective primary mouth is formed; and fourth, the prime role of Pitx genes for establishment and later morphogenesis of oral region both in vertebrates and non-vertebrate chordates. PMID:22804777

Clinical potentials of human pluripotent stem cells in lung diseases

PubMed Central

2014-01-01

Lung possesses very limited regenerative capacity. Failure to maintain homeostasis of lung epithelial cell populations has been implicated in the development of many life-threatening pulmonary diseases leading to substantial morbidity and mortality worldwide, and currently there is no known cure for these end-stage pulmonary diseases. Embryonic stem cells (ESCs) and somatic cell-derived induced pluripotent stem cells (iPSCs) possess unlimited self-renewal capacity and great potential to differentiate to various cell types of three embryonic germ layers (ectodermal, mesodermal, and endodermal). Therapeutic use of human ESC/iPSC-derived lung progenitor cells for regeneration of injured or diseased lungs will have an enormous clinical impact. This article provides an overview of recent advances in research on pluripotent stem cells in lung tissue regeneration and discusses technical challenges that must be overcome for their clinical applications in the future. PMID:24995122

Variable combinations of specific ephrin ligand/Eph receptor pairs control embryonic tissue separation.

PubMed

Rohani, Nazanin; Parmeggiani, Andrea; Winklbauer, Rudolf; Fagotto, François

2014-09-01

Ephrins and Eph receptors are involved in the establishment of vertebrate tissue boundaries. The complexity of the system is puzzling, however in many instances, tissues express multiple ephrins and Ephs on both sides of the boundary, a situation that should in principle cause repulsion between cells within each tissue. Although co-expression of ephrins and Eph receptors is widespread in embryonic tissues, neurons, and cancer cells, it is still unresolved how the respective signals are integrated into a coherent output. We present a simple explanation for the confinement of repulsion to the tissue interface: Using the dorsal ectoderm-mesoderm boundary of the Xenopus embryo as a model, we identify selective functional interactions between ephrin-Eph pairs that are expressed in partial complementary patterns. The combined repulsive signals add up to be strongest across the boundary, where they reach sufficient intensity to trigger cell detachments. The process can be largely explained using a simple model based exclusively on relative ephrin and Eph concentrations and binding affinities. We generalize these findings for the ventral ectoderm-mesoderm boundary and the notochord boundary, both of which appear to function on the same principles. These results provide a paradigm for how developmental systems may integrate multiple cues to generate discrete local outcomes.

Engineering epithelial-stromal interactions in vitro for toxicology assessment

EPA Science Inventory

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo t...

Auto Transplant for High Risk or Relapsed Solid or CNS Tumors

ClinicalTrials.gov

2018-04-24

Ewing's Family Tumors; Renal Tumors; Hepatoblastoma; Rhabdomyosarcoma; Soft Tissue Sarcoma; Primary Malignant Brain Neoplasms; Retinoblastoma; Medulloblastoma; Supra-tentorial Primative Neuro-Ectodermal Tumor (PNET); Atypical Teratoid/Rhabdoid Tumor (AT/RT); CNS Tumors; Germ Cell Tumors

Nonstimulated human uncommitted mesenchymal stem cells express cell markers of mesenchymal and neural lineages.

PubMed

Minguell, José J; Fierro, Fernando A; Epuñan, María J; Erices, Alejandro A; Sierralta, Walter D

2005-08-01

Ex vivo cultures of human bone marrow-derived mesenchymal stem cells (MSCs) contain subsets of progenitors exhibiting dissimilar properties. One of these subsets comprises uncommitted progenitors displaying distinctive features, such as morphology, a quiescent condition, growth factor production, and restricted tissue biodistribution after transplantation. In this study, we assessed the competence of these cells to express, in the absence of differentiation stimuli, markers of mesoderm and ectodermic (neural) cell lineages. Fluorescence microscopy analysis showed a unique pattern of expression of osteogenic, chondrogenic, muscle, and neural markers. The depicted "molecular signature" of these early uncommitted progenitors, in the absence of differentiation stimuli, is consistent with their multipotentiality and plasticity as suggested by several in vitro and in vivo studies.

[Clinical and molecular study in a family with autosomal dominant hypohidrotic ectodermal dysplasia].

PubMed

Callea, Michele; Cammarata-Scalisi, Francisco; Willoughby, Colin E; Giglio, Sabrina R; Sani, Ilaria; Bargiacchi, Sara; Traficante, Giovanna; Bellacchio, Emanuele; Tadini, Gianluca; Yavuz, Izzet; Galeotti, Angela; Clarich, Gabriella

2017-02-01

Hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by deficiency in development of structure derived from the ectoderm and is caused by mutations in the genes EDA, EDAR, or EDARADD. Phenotypes caused by mutations in these three may exhibit similar clinical features, explained by a common signaling pathway. Mutations in EDA gene cause X linked HED, which is the most common form. Mutations in EDAR and EDARADD genes cause autosomal dominant and recessive form of HED. The most striking clinical findings in HED are hypodontia, hypotrichosis and hypohidrosis that can lead to episodes of hyperthermia. We report on clinical findings in a child with HED with autosomal dominant inheritance pattern with a heterozygous mutation c.1072C>T (p.Arg358X) in the EDAR gene. A review of the literature with regard to other cases presenting the same mutation has been carried out and discussed. Sociedad Argentina de Pediatría.

Novel variant in the TP63 gene associated to ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome.

PubMed

Gonzalez, Francisco; Loidi, Lourdes; Abalo-Lojo, Jose M

2017-01-01

Ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) syndrome is a disorder resulting from anomalous embryonic development of ectodermal tissues. There is evidence that AEC syndrome is caused by mutations in the TP63 gene, which encodes the p63 protein. This is an important regulatory protein involved in epidermal proliferation and differentiation. Genome sequencing was performed in DNA from peripheral blood leukocytes of a newborn with AEC syndrome and her parents. Variants were searched in all coding exons and intron-exon boundaries of the TP63 gene. A heterozygous missense variant (NM_003722.4:c.1063G>C (p.Asp355His) was found in the newborn patient. No variants were found in either of the parents. We identified a previously unreported variant in TP63 gene which seems to be involved in the somatic malformations found in the AEC syndrome. The absence of this variant in both parents suggests that the variant appeared de novo.

Coordination of Cellular Dynamics Contributes to Tooth Epithelium Deformations

PubMed Central

Morita, Ritsuko; Kihira, Miho; Nakatsu, Yousuke; Nomoto, Yohei; Ogawa, Miho; Ohashi, Kazumasa; Mizuno, Kensaku; Tachikawa, Tetsuhiko; Ishimoto, Yukitaka; Morishita, Yoshihiro; Tsuji, Takashi

2016-01-01

The morphologies of ectodermal organs are shaped by appropriate combinations of several deformation modes, such as invagination and anisotropic tissue elongation. However, how multicellular dynamics are coordinated during deformation processes remains to be elucidated. Here, we developed a four-dimensional (4D) analysis system for tracking cell movement and division at a single-cell resolution in developing tooth epithelium. The expression patterns of a Fucci probe clarified the region- and stage-specific cell cycle patterns within the tooth germ, which were in good agreement with the pattern of the volume growth rate estimated from tissue-level deformation analysis. Cellular motility was higher in the regions with higher growth rates, while the mitotic orientation was significantly biased along the direction of tissue elongation in the epithelium. Further, these spatio-temporal patterns of cellular dynamics and tissue-level deformation were highly correlated with that of the activity of cofilin, which is an actin depolymerization factor, suggesting that the coordination of cellular dynamics via actin remodeling plays an important role in tooth epithelial morphogenesis. Our system enhances the understanding of how cellular behaviors are coordinated during ectodermal organogenesis, which cannot be observed from histological analyses. PMID:27588418

Epithelial stratification and placode invagination are separable functions in early morphogenesis of the molar tooth

PubMed Central

Li, Jingjing; Chatzeli, Lemonia; Panousopoulou, Eleni; Tucker, Abigail S.; Green, Jeremy B. A.

2016-01-01

Ectodermal organs, which include teeth, hair follicles, mammary ducts, and glands such as sweat, mucous and sebaceous glands, are initiated in development as placodes, which are epithelial thickenings that invaginate and bud into the underlying mesenchyme. These placodes are stratified into a basal and several suprabasal layers of cells. The mechanisms driving stratification and invagination are poorly understood. Using the mouse molar tooth as a model for ectodermal organ morphogenesis, we show here that vertical, stratifying cell divisions are enriched in the forming placode and that stratification is cell division dependent. Using inhibitor and gain-of-function experiments, we show that FGF signalling is necessary and sufficient for stratification but not invagination as such. We show that, instead, Shh signalling is necessary for, and promotes, invagination once suprabasal tissue is generated. Shh-dependent suprabasal cell shape suggests convergent migration and intercalation, potentially accounting for post-stratification placode invagination to bud stage. We present a model in which FGF generates suprabasal tissue by asymmetric cell division, while Shh triggers cell rearrangement in this tissue to drive invagination all the way to bud formation. PMID:26755699

Morphology of isolated mouse inner cell masses developing in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiley, L.M.; Spindle, A.I.; Pedersen, R.A.

1978-01-01

The purpose of this study was to examine the developmental capacity of the mouse inner cell mass (ICM) in the absence of the trophoblast. ICMs were isolated from blastocysts by immunosurgery and cultured under conditions that support egg cylinder formation by intact blastocysts. After 2 or 3 days of culture, the ICMs consisted of an outer layer of endoderm and an inner layer of ectoderm that had cavitated centrally. By 4 or 5 days of culture, 25 to 60% of these ICMs had developed into paired cysts, apparently by secondary cavity formation. The inner cell layer surrounding this secondary cavitymore » resembled the extraembryonic ectoderm of cultured egg cylinders. By 6 days of culture, 60% of the ICMs had expanded into yolk sac-like structures that subsequently produced capillaries containing blood cells. The ICMs appeared to develop mesoderm in two distinct ways. A few of them developed mesoderm as a third layer of cells in the cleft separating endoderm and ectoderm, presumably by migrating from the inner, ectodermal layer, through the primitive streak, as in the intact egg cylinder. In the rest of the ICMs the embryonic ectoderm gradually differentiated into mesoderm while still in the inner layer, without primitive streak formation. We suggest, therefore, that the continuous presence of the trophoblast or of its derivatives is not required for the cytodifferentiation of mesoderm although it may be important in establishing embryonic polarity or in providinginductive signals necessary for the morphogenetic aspects of mesoderm differentiation, specifically primitive streak formation.« less

Identification of a spatially specific enhancer element in the chicken Msx-2 gene that regulates its expression in the apical ectodermal ridge of the developing limb buds of transgenic mice.

PubMed

Sumoy, L; Wang, C K; Lichtler, A C; Pierro, L J; Kosher, R A; Upholt, W B

1995-07-01

Msx-2 is a member of the Msx family of homeobox-containing genes expressed in a variety of embryonic tissues involved in epithelial-mesenchymal interactions and pattern formation. In the developing chick limb bud, Msx-2 is expressed in the apical ectodermal ridge, which plays a crucial role in directing the growth and patterning of limb mesoderm. In addition, Msx-2 is expressed in the anterior nonskeletal-forming mesoderm of the limb bud, in the posterior necrotic zone, and in the interdigital mesenchyme. Studies of the altered expression patterns of Msx-2 in amelic and polydactylous mutant chick limbs have suggested that the apical ectodermal ridge and mesodermal domains of Msx-2 expression are independently regulated and that there might be separate cis-regulatory elements in the Msx-2 gene controlling its spatially distinct domains of expression. To test this hypothesis, we have isolated the chicken Msx-2 gene and have tested the ability of various regions of the gene to target expression of LacZ reporter gene to specific regions of the limbs of transgenic mice. A variety of these constructs are consistently expressed only in the apical ectodermal ridge and the ectoderm of the genital tubercle and are not expressed in the mesoderm of the limb bud or in other regions of the embryo where the endogenous Msx-2 gene is expressed. These results suggest the presence of spatially specific cis-regulatory elements in the Msx-2 gene. We identified a 348-bp region in the 5' flanking region of the Msx-2 gene which can act as an apical ectodermal ridge enhancer element when placed in reverse orientation in front of the reporter gene with transcription initiation directed by the minimal hsp68 promoter.

[Association of folate metabolism genes MTRR and MTHFR with complex congenital abnormalities among Chinese population in Shanxi Province, China].

PubMed

Zhang, Qin; Bai, Bao-Ling; Liu, Xiao-Zhen; Miao, Chun-Yue; Li, Hui-Li

2014-08-01

To explore the association of polymorphisms in folate metabolism genes, methionine synthase reductase (MTRR) gene and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, with complex congenital abnormalities and to further investigate its association with complex congenital abnormalities derived from three germ layers. A total of 250 cases of birth defects (with complex congenital abnormalities including congenital heart disease, neural tube defects, and craniofacial anomalies) in Shanxi Province, China were included in the study. MTRR single nucleotide polymorphism (SNP) (rs1801394) and MTHFR SNP (rs1801133) were genotyped by the SNaPshot method, and the genotyping results were compared with those of controls (n=420). SNPs rs1801394 and rs1801133 were associated with multiple birth defects. For the recessive model, individuals with GG genotype at rs1801394 and CC genotype at rs1801133 had a relatively low risk of developing birth defects, so the two genotypes were protective factors against birth defects. The homozygous recessive genotype at rs1801133, which served as a protective factor, was associated with ectoderm- or endoderm-derived complex congenital abnormalities, while the homozygous recessive genotype at rs1801394, which served as a protective factor, was associated with ectoderm-, mesoderm- or endoderm-derived complex congenital abnormalities. Among the Chinese population in Shanxi Province, the SNPs in folate metabolism genes (MTRR and MTHFR) are associated with complex congenital abnormalities and related to ectoderm, mesoderm or endoderm development.

Quantitative proteomics of the human skin secretome reveal a reduction in immune defense mediators in ectodermal dysplasia patients.

PubMed

Burian, Marc; Velic, Ana; Matic, Katarina; Günther, Stephanie; Kraft, Beatrice; Gonser, Lena; Forchhammer, Stephan; Tiffert, Yvonne; Naumer, Christian; Krohn, Michael; Berneburg, Mark; Yazdi, Amir S; Maček, Boris; Schittek, Birgit

2015-03-01

In healthy human skin host defense molecules such as antimicrobial peptides (AMPs) contribute to skin immune homeostasis. In patients with the congenital disease ectodermal dysplasia (ED) skin integrity is disturbed and as a result patients have recurrent skin infections. The disease is characterized by developmental abnormalities of ectodermal derivatives and absent or reduced sweating. We hypothesized that ED patients have a reduced skin immune defense because of the reduced ability to sweat. Therefore, we performed a label-free quantitative proteome analysis of wash solution of human skin from ED patients or healthy individuals. A clear-cut difference between both cohorts could be observed in cellular processes related to immunity and host defense. In line with the extensive underrepresentation of proteins of the immune system, dermcidin, a sweat-derived AMP, was reduced in its abundance in the skin secretome of ED patients. In contrast, proteins involved in metabolic/catabolic and biosynthetic processes were enriched in the skin secretome of ED patients. In summary, our proteome profiling provides insights into the actual situation of healthy versus diseased skin. The systematic reduction in immune system and defense-related proteins may contribute to the high susceptibility of ED patients to skin infections and altered skin colonization.

Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate

PubMed Central

Mederacke, Ingmar; Komatsu, Yoshihiro; Stice, Steve; Schwabe, Robert F.; Mistretta, Charlotte M.; Mishina, Yuji; Liu, Hong-Xiang

2016-01-01

Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5) and young postnatal (P1-10) mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT) to mature taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1) P0-Cre/R26-tdTomato (RFP) to label NC, NC derived Schwann cells and derivatives; (2) Dermo1-Cre/RFP to label mesenchymal cells and derivatives; and (3) Vimentin-CreER/mGFP to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both P0-Cre/RFP and Dermo1-Cre/RFP labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III) of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further, Vimentin-CreER labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC. PMID:26741369

Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate.

PubMed

Boggs, Kristin; Venkatesan, Nandakumar; Mederacke, Ingmar; Komatsu, Yoshihiro; Stice, Steve; Schwabe, Robert F; Mistretta, Charlotte M; Mishina, Yuji; Liu, Hong-Xiang

2016-01-01

Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5) and young postnatal (P1-10) mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT) to mature taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1) P0-Cre/R26-tdTomato (RFP) to label NC, NC derived Schwann cells and derivatives; (2) Dermo1-Cre/RFP to label mesenchymal cells and derivatives; and (3) Vimentin-CreER/mGFP to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both P0-Cre/RFP and Dermo1-Cre/RFP labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III) of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further, Vimentin-CreER labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC.

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine.

PubMed

Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C; Nolta, Jan A; Athanasiou, Kyriacos A

2015-10-01

The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use. ©AlphaMed Press.

Concise Review: Human Dermis as an Autologous Source of Stem Cells for Tissue Engineering and Regenerative Medicine

PubMed Central

Vapniarsky, Natalia; Arzi, Boaz; Hu, Jerry C.; Nolta, Jan A.

2015-01-01

The exciting potential for regenerating organs from autologous stem cells is on the near horizon, and adult dermis stem cells (DSCs) are particularly appealing because of the ease and relative minimal invasiveness of skin collection. A substantial number of reports have described DSCs and their potential for regenerating tissues from mesenchymal, ectodermal, and endodermal lineages; however, the exact niches of these stem cells in various skin types and their antigenic surface makeup are not yet clearly defined. The multilineage potential of DSCs appears to be similar, despite great variability in isolation and in vitro propagation methods. Despite this great potential, only limited amounts of tissues and clinical applications for organ regeneration have been developed from DSCs. This review summarizes the literature on DSCs regarding their niches and the specific markers they express. The concept of the niches and the differentiation capacity of cells residing in them along particular lineages is discussed. Furthermore, the advantages and disadvantages of widely used methods to demonstrate lineage differentiation are considered. In addition, safety considerations and the most recent advancements in the field of tissue engineering and regeneration using DSCs are discussed. This review concludes with thoughts on how to prospectively approach engineering of tissues and organ regeneration using DSCs. Our expectation is that implementation of the major points highlighted in this review will lead to major advancements in the fields of regenerative medicine and tissue engineering. Significance Autologous dermis-derived stem cells are generating great excitement and efforts in the field of regenerative medicine and tissue engineering. The substantial impact of this review lies in its critical coverage of the available literature and in providing insight regarding niches, characteristics, and isolation methods of stem cells derived from the human dermis. Furthermore, it provides analysis of the current state-of-the-art regenerative approaches using human-derived dermal stem cells, with consideration of current guidelines, to assist translation toward therapeutic use. PMID:26253713

The fine structure of human germ layers in vivo: clues to the early differentiation of embryonic stem cells in vitro.

PubMed

Sathananthan, Henry; Selvaraj, Kamala; Clark, Joan

2011-08-01

The fine structure of the three germ layers in human ectopic embryos (stage 7) have been documented by digital light and electron microscopy. The formation of ectoderm, endoderm and mesoderm and notochordal cells, and also the extraembryonic membranes, amnion and yolk sac, are imaged. The germ layers give rise to all the cells and tissues of the human body. Possible clues to the early differentiation of embryonic stem cells (ESC) in vitro were obtained, since these events are more or less mimicked in cultures of ESC derived from the inner cell mass of human blastocysts. The findings are discussed with reference to previous studies on the fine structure of ESC using the same technique. Copyright © 2011. Published by Elsevier Ltd.

Somatic Donor Cell Type Correlates with Embryonic, but Not Extra-Embryonic, Gene Expression in Postimplantation Cloned Embryos

PubMed Central

Inoue, Kimiko; Ogura, Atsuo

2013-01-01

The great majority of embryos generated by somatic cell nuclear transfer (SCNT) display defined abnormal phenotypes after implantation, such as an increased likelihood of death and abnormal placentation. To gain better insight into the underlying mechanisms, we analyzed genome-wide gene expression profiles of day 6.5 postimplantation mouse embryos cloned from three different cell types (cumulus cells, neonatal Sertoli cells and fibroblasts). The embryos retrieved from the uteri were separated into embryonic (epiblast) and extraembryonic (extraembryonic ectoderm and ectoplacental cone) tissues and were subjected to gene microarray analysis. Genotype- and sex-matched embryos produced by in vitro fertilization were used as controls. Principal component analysis revealed that whereas the gene expression patterns in the embryonic tissues varied according to the donor cell type, those in extraembryonic tissues were relatively consistent across all groups. Within each group, the embryonic tissues had more differentially expressed genes (DEGs) (>2-fold vs. controls) than did the extraembryonic tissues (P<1.0×10–26). In the embryonic tissues, one of the common abnormalities was upregulation of Dlk1, a paternally imprinted gene. This might be a potential cause of the occasional placenta-only conceptuses seen in SCNT-generated mouse embryos (1–5% per embryos transferred in our laboratory), because dysregulation of the same gene is known to cause developmental failure of embryos derived from induced pluripotent stem cells. There were also some DEGs in the extraembryonic tissues, which might explain the poor development of SCNT-derived placentas at early stages. These findings suggest that SCNT affects the embryonic and extraembryonic development differentially and might cause further deterioration in the embryonic lineage in a donor cell-specific manner. This could explain donor cell-dependent variations in cloning efficiency using SCNT. PMID:24146866

Ectrodactyly-ectodermal dysplasia clefting syndrome (EEC syndrome).

PubMed

Koul, Monika; Dwivedi, Rahul; Upadhyay, Vinod

2014-01-01

Ectrodactyly-ectodermal dysplasia- clefting syndrome (also k/a. split hand- split foot malformation /split hand-split foot ectodermal dysplasia- cleft syndrome/ectodermal dysplasia cleft lip/cleft palate syndrome) a rare form of ectodermal dysplasia, is an autosomal dominant disorder inherited as a genetic trait and characterized by a triad of (i) ectrodactyly, (ii) ectodermal dysplasia and, (iii) & facial clefts.

EEC- and ADULT-associated TP63 mutations exhibit functional heterogeneity toward P63 responsive sequences.

PubMed

Monti, Paola; Russo, Debora; Bocciardi, Renata; Foggetti, Giorgia; Menichini, Paola; Divizia, Maria T; Lerone, Margherita; Graziano, Claudio; Wischmeijer, Anita; Viadiu, Hector; Ravazzolo, Roberto; Inga, Alberto; Fronza, Gilberto

2013-06-01

TP63 germ-line mutations are responsible for a group of human ectodermal dysplasia syndromes, underlining the key role of P63 in the development of ectoderm-derived tissues. Here, we report the identification of two TP63 alleles, G134V (p.Gly173Val) and insR155 (p.Thr193_Tyr194insArg), associated to ADULT and EEC syndromes, respectively. These alleles, along with previously identified G134D (p.Gly173Asp) and R204W (p.Arg243Trp), were functionally characterized in yeast, studied in a mammalian cell line and modeled based on the crystal structure of the P63 DNA-binding domain. Although the p.Arg243Trp mutant showed both complete loss of transactivation function and ability to interfere over wild-type P63, the impact of p.Gly173Asp, p.Gly173Val, and p.Thr193_Tyr194insArg varied depending on the response element (RE) tested. Interestingly, p.Gly173Asp and p.Gly173Val mutants were characterized by a severe defect in transactivation along with interfering ability on two DN-P63α-specific REs derived from genes closely related to the clinical manifestations of the TP63-associated syndromes, namely PERP and COL18A1. The modeling of the mutations supported the distinct functional effect of each mutant. The present results highlight the importance of integrating different functional endpoints that take in account the features of P63 proteins' target sequences to examine the impact of TP63 mutations and the associated clinical variability. © 2013 Wiley Periodicals, Inc.

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development

PubMed Central

Lough, Kendall J.; Patel, Jeet H.; Descovich, Carlos Patiño; Curtis, T. Anthony

2016-01-01

Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation. PMID:27317810

A novel missense mutation in the gene EDARADD associated with an unusual phenotype of hypohidrotic ectodermal dysplasia.

PubMed

Wohlfart, Sigrun; Söder, Stephan; Smahi, Asma; Schneider, Holm

2016-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare disorder characterized by deficient development of structures derived from the ectoderm including hair, nails, eccrine glands, and teeth. HED forms that are caused by mutations in the genes EDA, EDAR, or EDARADD may show almost identical phenotypes, explained by a common signaling pathway. Proper interaction of the proteins encoded by these three genes is important for the activation of the NF-κB signaling pathway and subsequent transcription of the target genes. Mutations in the gene EDARADD are most rarely implicated in HED. Here we describe a novel missense mutation, c.367G>A (p.Asp123Asn), in this gene which did not appear to influence the interaction between EDAR and EDARADD proteins, but led to an impaired ability to activate NF-κB signaling. Female members of the affected family showed either unilateral or bilateral amazia. In addition, an affected girl developed bilateral ovarian teratomas, possibly associated with her genetic condition. © 2015 Wiley Periodicals, Inc.

Anhidrotic ectodermal dysplasia presenting as atrophic rhinitis.

PubMed

Barman, Debasis; Mandal, Satadal; Nandi, Santanu; Banerjee, Pranabashish; Rashid, M A

2011-11-01

Ectodermal dysplasia is a complex group of familial disorders with numerous clinical characteristics, with an incidence of 7 in 10000 born alive children. Ectodermal dysplasia affects structures of ectodermal origin like the skin and its appendages as well as other non-ectodermal structures. The most common sites of involvement are the defects in the skin, hair, teeth, nails and sweat glands,which are of ectodermal origin. Though the dermatologists and paediatricians often manage such cases, we report one case of ectodermal dysplasia presenting with atrophic rhinitis.

Apical and basal epitheliomuscular F-actin dynamics during Hydra bud evagination

PubMed Central

Aufschnaiter, Roland; Wedlich-Söldner, Roland; Zhang, Xiaoming

2017-01-01

ABSTRACT Bending of 2D cell sheets is a fundamental morphogenetic mechanism during animal development and reproduction. A critical player driving cell shape during tissue bending is the actin cytoskeleton. Much of our current knowledge about actin dynamics in whole organisms stems from studies of embryonic development in bilaterian model organisms. Here, we have analyzed actin-based processes during asexual bud evagination in the simple metazoan Hydra. We created transgenic Hydra strains stably expressing the actin marker Lifeact-GFP in either ectodermal or endodermal epitheliomuscular cells. We then combined live imaging with conventional phalloidin staining to directly follow actin reorganization. Bending of the Hydra epithelial double layer is initiated by a group of epitheliomuscular cells in the endodermal layer. These cells shorten their apical-basal axis and arrange their basal muscle processes in a circular configuration. We propose that this rearrangement generates the initial forces to bend the endoderm towards the ectoderm. Convergent tissue movement in both epithelial layers towards the centre of evagination then leads to elongation and extension of the bud along its new body axis. Tissue movement into the bud is associated with lateral intercalation of epithelial cells, remodelling of apical septate junctions, and rearrangement of basal muscle processes. The work presented here extends the analysis of morphogenetic mechanisms beyond embryonic tissues of model bilaterians. PMID:28630355

Learning about Vertebrate Limb Development

ERIC Educational Resources Information Center

Liang, Jennifer O.; Noll, Matthew; Olsen, Shayna

2014-01-01

We have developed an upper-level undergraduate laboratory exercise that enables students to replicate a key experiment in developmental biology. In this exercise, students have the opportunity to observe live chick embryos and stain the apical ectodermal ridge, a key tissue required for development of the vertebrate limb. Impressively, every…

Initiation of olfactory placode development and neurogenesis is blocked in mice lacking both Six1 and Six4.

PubMed

Chen, Binglai; Kim, Eun-Hee; Xu, Pin-Xian

2009-02-01

Mouse olfactory epithelium (OE) originates from ectodermally derived placode, the olfactory placode that arises at the anterior end of the neural plate. Tissue grafting and recombination experiments suggest that the placode is derived from a common preplacodal domain around the neural plate and its development is directed by signals arising from the underlying mesoderm and adjacent neuroectoderm. In mice, loss of Six1 affects OE morphogenesis but not placode formation. We show here that embryos lacking both Six1 and Six4 failed to form the olfactory placode but the preplacodal region appeared to be specified as judged by the expression of Eya2, which marks the common preplacodal domain, suggesting a synergistic requirement of Six1 and Six4 in patterning the preplacodal ectoderm to a morphologic placode. Our results show that Six1 and Six4 are coexpressed in the preplacodal ectoderm from E8.0. In the olfactory pit, Six4 expression was observed in the peripheral precursors that overlap with Mash1-expressing cells, the early committed neuronal lineage. In contrast, Six1 is highly distributed in the peripheral regions where stem cells reside at E10.5 and it overlaps with Sox2 expression. Both genes are expressed in the basal and apical neuronal progenitors in the OE. Analyses of Six1;Six4 double mutant embryos demonstrated that the slightly thickened epithelium observed in the mutant was not induced for neuronal development. In contrast, in Six1(-/-) embryos, all neuronal lineage markers were initially expressed but the pattern of their expression was altered. Although very few, the pioneer neurons were initially present in the Six1 mutant OE. However, neurogenesis ceased by E12.5 due to markedly increased cell apoptosis and reduced proliferation, thus defining the cellular defects occurring in Six1(-/-) OE that have not been previously observed. Our findings demonstrate that Six1/4 function at the top of early events controlling olfactory placode formation and neuronal development. Our analyses show that the threshold of Six1/4 may be crucial for the expression of olfactory specific genes and that Six1 and Six4 may act synergistically to mediate olfactory placode specification and patterning through Fgf and Bmp signaling pathways.

Hypohidrotic and hidrotic ectodermal dysplasia: a report of two cases.

PubMed

Vasconcelos Carvalho, Marianne; Romero Souto de Sousa, José; Paiva Correa de Melo, Filipe; Fonseca Faro, Tatiane; Nunes Santos, Ana Clara; Carvalho, Silvia; Veras Sobral, Ana Paula

2013-07-14

Ectodermal dysplasias are a large group of syndromes characterized by anomalies in the structures of ectodermal origin. There are 2 major types of this disorder, based on clinical findings: hypohidrotic ectodermal dysplasia and hidrotic ectodermal dysplasia. This clinical classification is very important because clinical professionals involved with this disease need first a clear and practical method of diagnosis. The main oral manifestation of ectodermal dysplasia may be expressed as hypodontia. Thus, dental professionals may be the first to diagnose ectodermal dysplasia. The present article reports one case of each of the main types (hypohidrotic and hidrotic) of ectodermal dysplasia and the authors review the literature regarding the pathogenesis, clinical features, and therapeutic management of this condition.

Physiological responses to heat of resting man with impaired sweating capacity

NASA Technical Reports Server (NTRS)

Totel, G. L.

1974-01-01

The effects of total-body heat exposure were studied in three groups of subjects with varied degrees of impaired sweating capacity. The responses of two ectodermal dysplasic men, six quadriplegic men, and a man with widespread burned scar tissue were compared with the responses of three able-bodied men resting in the heat. It was found that the able-bodied and burned subjects competed successfully with a controlled environment of 38 C and 20% relative humidity for up to 150 min, whereas the quadriplegic and ectodermal dysplasic men developed hyperthermia, hyperventilation, and distress after only 120 and 75 min of heat exposure, respectively. The intolerance to heat is thus ascribed directly to the inability to produce and evaporate sweat.

EDARV370A associated facial characteristics in Uyghur population revealing further pleiotropic effects.

PubMed

Peng, Qianqian; Li, Jinxi; Tan, Jingze; Yang, Yajun; Zhang, Manfei; Wu, Sijie; Liu, Yu; Zhang, Juan; Qin, Pengfei; Guan, Yaqun; Jiao, Yi; Zhang, Zhaoxia; Sabeti, Pardis C; Tang, Kun; Xu, Shuhua; Jin, Li; Wang, Sijia

2016-01-01

An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.

Wise promotes coalescence of cells of neural crest and placode origins in the trigeminal region during head development.

PubMed

Shigetani, Yasuyo; Howard, Sara; Guidato, Sonia; Furushima, Kenryo; Abe, Takaya; Itasaki, Nobue

2008-07-15

While most cranial ganglia contain neurons of either neural crest or placodal origin, neurons of the trigeminal ganglion derive from both populations. The Wnt signaling pathway is known to be required for the development of neural crest cells and for trigeminal ganglion formation, however, migrating neural crest cells do not express any known Wnt ligands. Here we demonstrate that Wise, a Wnt modulator expressed in the surface ectoderm overlying the trigeminal ganglion, play a role in promoting the assembly of placodal and neural crest cells. When overexpressed in chick, Wise causes delamination of ectodermal cells and attracts migrating neural crest cells. Overexpression of Wise is thus sufficient to ectopically induce ganglion-like structures consisting of both origins. The function of Wise is likely synergized with Wnt6, expressed in an overlapping manner with Wise in the surface ectoderm. Electroporation of morpholino antisense oligonucleotides against Wise and Wnt6 causes decrease in the contact of neural crest cells with the delaminated placode-derived cells. In addition, targeted deletion of Wise in mouse causes phenotypes that can be explained by a decrease in the contribution of neural crest cells to the ophthalmic lobe of the trigeminal ganglion. These data suggest that Wise is able to function cell non-autonomously on neural crest cells and promote trigeminal ganglion formation.

Neural transcription factors bias cleavage stage blastomeres to give rise to neural ectoderm

PubMed Central

Gaur, Shailly; Mandelbaum, Max; Herold, Mona; Majumdar, Himani Datta; Neilson, Karen M.; Maynard, Thomas M.; Mood, Kathy; Daar, Ira O.; Moody, Sally A.

2016-01-01

The decision by embryonic ectoderm to give rise to epidermal versus neural derivatives is the result of signaling events during blastula and gastrula stages. However, there also is evidence in Xenopus that cleavage stage blastomeres contain maternally derived molecules that bias them toward a neural fate. We used a blastomere explant culture assay to test whether maternally deposited transcription factors bias 16-cell blastomere precursors of epidermal or neural ectoderm to express early zygotic neural genes in the absence of gastrulation interactions or exogenously supplied signaling factors. We found that Foxd4l1, Zic2, Gmnn and Sox11 each induced explants made from ventral, epidermis-producing blastomeres to express early neural genes, and that at least some of the Foxd4l1 and Zic2 activity is required at cleavage stages. Similarly, providing extra Foxd4l1 or Zic2 to explants made from dorsal, neural plate-producing blastomeres significantly increased expression of early neural genes, whereas knocking down either significantly reduced them. These results show that maternally delivered transcription factors bias cleavage stage blastomeres to a neural fate. We demonstrate that mouse and human homologues of Foxd4l1 have similar functional domains compared to the frog protein, as well as conserved transcriptional activities when expressed in Xenopus embryos and blastomere explants. PMID:27092474

Dynamic 3D culture promotes spontaneous embryonic stem cell differentiation in vitro.

PubMed

Gerlach, Jörg C; Hout, Mariah; Edsbagge, Josefina; Björquist, Petter; Lübberstedt, Marc; Miki, Toshio; Stachelscheid, Harald; Schmelzer, Eva; Schatten, Gerald; Zeilinger, Katrin

2010-02-01

Spontaneous in vitro differentiation of mouse embryonic stem cells (mESC) is promoted by a dynamic, three-dimensional (3D), tissue-density perfusion technique with continuous medium perfusion and exchange in a novel four-compartment, interwoven capillary bioreactor. We compared ectodermal, endodermal, and mesodermal immunoreactive tissue structures formed by mESC at culture day 10 with mouse fetal tissue development at gestational day E9.5. The results show that the bioreactor cultures more closely resemble mouse fetal tissue development at gestational day E9.5 than control mESC cultured in Petri dishes.

Mechanics of Fluid-Filled Interstitial Gaps. II. Gap Characteristics in Xenopus Embryonic Ectoderm.

PubMed

Barua, Debanjan; Parent, Serge E; Winklbauer, Rudolf

2017-08-22

The ectoderm of the Xenopus embryo is permeated by a network of channels that appear in histological sections as interstitial gaps. We characterized this interstitial space by measuring gap sizes, angles formed between adjacent cells, and curvatures of cell surfaces at gaps. From these parameters, and from surface-tension values measured previously, we estimated the values of critical mechanical variables that determine gap sizes and shapes in the ectoderm, using a general model of interstitial gap mechanics. We concluded that gaps of 1-4 μm side length can be formed by the insertion of extracellular matrix fluid at three-cell junctions such that cell adhesion is locally disrupted and a tension difference between cell-cell contacts and the free cell surface at gaps of 0.003 mJ/m 2 is generated. Furthermore, a cell hydrostatic pressure of 16.8 ± 1.7 Pa and an interstitial pressure of 3.9 ± 3.6 Pa, relative to the central blastocoel cavity of the embryo, was found to be consistent with the observed gap size and shape distribution. Reduction of cell adhesion by the knockdown of C-cadherin increased gap volume while leaving intracellular and interstitial pressures essentially unchanged. In both normal and adhesion-reduced ectoderm, cortical tension of the free cell surfaces at gaps does not return to the high values characteristic of the free surface of the whole tissue. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Histology and ultrastructure of the coenenchyme of the octocoral Swiftia exserta, a model organism for innate immunity/graft rejection.

PubMed

Menzel, L P; Tondo, C; Stein, B; Bigger, C H

2015-04-01

The octocoral Swiftia exserta has been utilized extensively in our laboratory to study innate immune reactions in Cnidaria such as wound healing, auto- and allo-graft reactions, and for some classical "foreign body" phagocytosis experiments. All of these reactions occur in the coenenchyme of the animal, the colonial tissue surrounding the axial skeleton in which the polyps are embedded, and do not rely on nematocysts or directly involve the polyps. In order to better understand some of the cellular reactions occurring in the coenenchyme, the present study employed several cytochemical methods (periodic acid-Schiff reaction, Mallory's aniline blue collagen stain, and Gomori's trichrome stain) and correlated the observed structures with electron microscopy (both scanning and transmission). Eight types of cells were apparent in the coenenchyme of S. exserta, exclusive of gastrodermal tissue: (i) epithelial ectoderm cells, (ii) oblong granular cells, (iii) granular amoebocytes, (iv) morula-like cells, (v) mesogleal cells, (vi) sclerocytes, (vii) axial epithelial cells, and (viii) cnidocytes with mostly atrichous isorhiza nematocysts. Several novel organizational features are now apparent from transmission electron micrographs: the ectoderm consists of a single layer of flat epithelial cells, the cell types of the mesoglea extend from beneath the thin ectoderm throughout the mesogleal cell cords, the organization of the solenia gastroderm consists of a single layer of cells, and two nematocyst types have been found. A new interpretation of the cellular architecture of S. exserta, and more broadly, octocoral biology is now possible. Copyright © 2014 Elsevier GmbH. All rights reserved.

Histology and ultrastructure of the coenenchyme of the octocoral Swiftia exserta, a model organism for innate immunity/graft rejection

PubMed Central

Menzel, L.P.; Tondo, C.; Stein, B.; Bigger, C.H.

2015-01-01

The octocoral Swiftia exserta has been utilized extensively in our laboratory to study innate immune reactions in Cnidaria such as wound healing, auto- and allo-graft reactions, and for some classical “foreign body” phagocytosis experiments. All of these reactions occur in the coenenchyme of the animal, the colonial tissue surrounding the axial skeleton in which the polyps are embedded, and do not rely on nematocysts or directly involve the polyps. In order to better understand some of the cellular reactions occurring in the coenenchyme, the present study employed several cytochemical methods (periodic acid–Schiff reaction, Mallory’s aniline blue collagen stain, and Gomori’s trichrome stain) and correlated the observed structures with electron microscopy (both scanning and transmission). Eight types of cells were apparent in the coenenchyme of S. exserta, exclusive of gastrodermal tissue: (i) epithelial ectoderm cells, (ii) oblong granular cells, (iii) granular amoebocytes, (iv) morula-like cells, (v) mesogleal cells, (vi) sclerocytes, (vii) axial epithelial cells, and (viii) cnidocytes with mostly atrichous isorhiza nematocysts. Several novel organizational features are now apparent from transmission electron micrographs: the ectoderm consists of a single layer of flat epithelial cells, the cell types of the mesoglea extend from beneath the thin ectoderm throughout the mesogleal cell cords, the organization of the solenia gastroderm consists of a single layer of cells, and two nematocyst types have been found. A new interpretation of the cellular architecture of S. exserta, and more broadly, octocoral biology is now possible. PMID:25596959

Laminin and integrin expression in the ventral ectodermal ridge of the mouse embryo: implications for regulation of BMP signalling.

PubMed

Lopez-Escobar, Beatriz; De Felipe, Beatriz; Sanchez-Alcazar, Jose Antonio; Sasaki, Takako; Copp, Andrew J; Ybot-Gonzalez, Patricia

2012-11-01

The ventral ectodermal ridge (VER) is an important signalling centre in the mouse tail-bud following completion of gastrulation. BMP regulation is essential for VER function, but how these signals are transmitted between adjacent tissues is unclear. We investigated the idea that extracellular matrix components might be involved, using immunohistochemistry and in situ hybridisation to detect all known α, β, and γ laminin chains and their mRNAs in the early tail bud. We identified an apparently novel laminin variant, comprising α5, β3 and γ2 chains, as a major component of the VER basement membrane at E9.5. Strikingly, only the mRNAs for these chains were co-expressed in VER cells, suggesting that lamin532 may be the sole basement membrane laminin at this stage. Since α6 integrin was also expressed in VER cells, this raises the possibility of cell-matrix interactions regulating BMP signalling at this site of caudal morphogenesis. Laminin532 could interact with α6-containing integrin to direct differentiation of the specialised VER cells from surface ectoderm. Copyright © 2012 Wiley Periodicals, Inc.

Laminin and integrin expression in the ventral ectodermal ridge of the mouse embryo: implications for regulation of BMP signalling

PubMed Central

Lopez-Escobar, Beatriz; de Felipe, Beatriz; Sanchez-Alcazar, Jose Antonio; Sasaki, Takako; Copp, Andrew J.; Ybot-Gonzalez, Patricia

2013-01-01

Background The ventral ectodermal ridge (VER) is an important signalling centre in the mouse tail-bud following completion of gastrulation. BMP regulation is essential for VER function, but how these signals are transmitted between adjacent tissues is unclear. Results We investigated the idea that extracellular matrix components might be involved, using immunohistochemistry and in situ hybridisation to detect all known α, β and γ laminin chains and their mRNAs in the early tail bud. We identified an apparently novel laminin variant, comprising α5, β3 and γ2 chains, as a major component of the VER basement membrane at E9.5. Strikingly, only the mRNAs for these chains were co-expressed in VER cells, suggesting that lamin532 may be the sole basement membrane laminin at this stage. Since α6 integrin was also expressed in VER cells, this raises the possibility of cell-matrix interactions regulating BMP signalling at this site of caudal morphogenesis. Conclusions Laminin532 could interact with α6-containing integrin to direct differentiation of the specialised VER cells from surface ectoderm. PMID:22911573

Non-neural ectoderm is really neural: evolution of developmental patterning mechanisms in the non-neural ectoderm of chordates and the problem of sensory cell homologies.

PubMed

Holland, Linda Z

2005-07-15

In chordates, the ectoderm is divided into the neuroectoderm and the so-called non-neural ectoderm. In spite of its name, however, the non-neural ectoderm contains numerous sensory cells. Therefore, the term "non-neural" ectoderm should be replaced by "general ectoderm." At least in amphioxus and tunicates and possibly in vertebrates as well, both the neuroectoderm and the general ectoderm are patterned anterior/posteriorly by mechanisms involving retinoic acid and Hox genes. In amphioxus and tunicates the ectodermal sensory cells, which have a wide range of ciliary and microvillar configurations, are mostly primary neurons sending axons to the CNS, although a minority lack axons. In contrast, vertebrate mechanosensory cells, called hair cells, are all secondary neurons that lack axons and have a characteristic eccentric cilium adjacent to a group of microvilli of graded lengths. It has been highly controversial whether the ectodermal sensory cells in the oral siphons of adult tunicates are homologous to vertebrate hair cells. In some species of tunicates, these cells appear to be secondary neurons, and microvillar and ciliary configurations of some of these cells approach those of vertebrate hair cells. However, none of the tunicate cells has all the characteristics of a hair cell, and there is a high degree of variation among ectodermal sensory cells within and between different species. Thus, similarities between the ectodermal sensory cells of any one species of tunicate and craniate hair cells may well represent convergent evolution rather than homology. Copyright 2005 Wiley-Liss, Inc.

Derivation of Stromal (Skeletal and Mesenchymal) Stem-Like Cells from Human Embryonic Stem Cells

PubMed Central

Harkness, Linda; Abdallah, Basem M.; Elsafadi, Mona; Al-Nbaheen, May S.; Aldahmash, Abdullah; Kassem, Moustapha

2012-01-01

Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESCs) is a prerequisite for their use in clinical applications. However, there is no standard protocol for differentiating hESCs into osteoblastic cells. The aim of this study was to identify the emergence of a human stromal (mesenchymal and skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESCs in a feeder-free environment using serum replacement and as suspension aggregates (embryoid bodies; hEBs). Over a 20 day developmental period, the hEBs demonstrated increasing enrichment for cells expressing hMSC markers: CD29, CD44, CD63, CD56, CD71, CD73, CD105, CD106, and CD166 as revealed by immunohistochemical staining and flow cytometry (fluorescence-activated cell sorting) analysis. Ex vivo differentiation of hEBs using bone morphogenic protein 2 (BMP2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold, revealed bone and cartilage, and fibrous tissue elements after 8 weeks. These tissues were of human origin and there was no evidence of differentiation to nonmesodermal tissues. hEBs implanted in the absence of HA/TCP formed vacuolated tissue containing glandular, fibrous and muscle-like tissue elements. Conversely, implantation of undifferentiated hESCs resulted in the formation of a teratoma containing a mixture of endodermal, mesodermal, and ectodermal tissues. Our study demonstrates that hMSC-like cells can be obtained from hESCs and they can be induced to form skeletal tissues in vivo when combined with HA/TCP. These findings are relevant for tissue engineering and suggest that differentiated hEBs can provide an unlimited source for functional osteogenic cells. PMID:22612317

C-kit+ cells isolated from developing kidneys are a novel population of stem cells with regenerative potential

PubMed Central

Rangel, Erika B; Gomes, Samirah A; Dulce, Raul A; Premer, Courtney; Rodrigues, Claudia O; Kanashiro-Takeuchi, Rosemeire M; Oskouei, Behzad; Carvalho, Decio A; Ruiz, Phillip; Reiser, Jochen; Hare, Joshua M

2013-01-01

The presence of tissue specific precursor cells is an emerging concept in organ formation and tissue homeostasis. Several progenitors are described in the kidneys. However, their identity as a true stem cell remains elusive. Here, we identify a neonatal kidney-derived c-kit+ cell population that fulfills all of the criteria as a stem cell. These cells were found in the thick ascending limb of Henle's loop and exhibited clonogenicity, self-renewal, and multipotentiality with differentiation capacity into mesoderm and ectoderm progeny. Additionally, c-kit+ cells formed spheres in nonadherent conditions when plated at clonal density and expressed markers of stem cells, progenitors, and differentiated cells. Ex-vivo expanded c-kit+ cells integrated into several compartments of the kidney, including tubules, vessels, and glomeruli, and contributed to functional and morphological improvement of the kidney following acute ischemia-reperfusion injury in rats. Together these findings document a novel neonatal rat kidney c-kit+ stem cell population that can be isolated, expanded, cloned, differentiated, and employed for kidney repair following acute kidney injury. These cells have important biological and therapeutic implications. PMID:23733311

Embryonic wound healing by apical contraction and ingression in Xenopus laevis.

PubMed

Davidson, Lance A; Ezin, Akouavi M; Keller, Ray

2002-11-01

We have characterized excisional wounds in the animal cap of early embryos of the frog Xenopus laevis and found that these wounds close accompanied by three distinct processes: (1) the assembly of an actin purse-string in the epithelial cells at the wound margin, (2) contraction and ingression of exposed deep cells, and (3) protrusive activity of epithelial cells at the margin. Microsurgical manipulation allowing fine control over the area and depth of the wound combined with videomicroscopy and confocal analysis enabled us to describe the kinematics and challenge the mechanics of the closing wound. Full closure typically occurs only when the deep, mesenchymal cell-layer of the ectoderm is left intact; in contrast, when deep cells are removed along with the superficial, epithelial cell-layer of the ectoderm, wounds do not close. Actin localizes to the superficial epithelial cell-layer at the wound margin immediately after wounding and forms a contiguous "purse-string" in those cells within 15 min. However, manipulation and closure kinematics of shaped wounds and microsurgical cuts made through the purse-string rule out a major force-generating role for the purse-string. Further analysis of the cell behaviors within the wound show that deep, mesenchymal cells contract their apical surfaces and ingress from the exposed surface. High resolution time-lapse sequences of cells at the leading edge of the wound show that these cells undergo protrusive activity only during the final phases of wound closure as the ectoderm reseals. We propose that assembly of the actin purse-string works to organize and maintain the epithelial sheet at the wound margin, that contraction and ingression of deep cells pulls the wound margins together, and that protrusive activity of epithelial cells at the wound margin reseals the ectoderm and re-establishes tissue integrity during wound healing in the Xenopus embryonic ectoderm. Copyright 2002 Wiley-Liss, Inc.

Perinatal Autopsy Findings in a Case of De Novo Hypohidrotic Ectodermal Dysplasia.

PubMed

Chikkannaiah, Panduranga; Nagaraju, Smitha; Kangle, Rajit; Gosavi, Mansi

2015-01-01

Ectodermal dysplasia are group of inherited disorders involving the developmental defects of ectodermal structures like hair, teeth, nails, sweat glands, and others. X-linked recessive inheritance is most common. Here we describe perinatal autopsy findings in a case of de novo ectodermal dysplasia in a female fetus. To the best of our knowledge, this is the first fetal autopsy description in a case of ectodermal dysplasia.

Planar induction of convergence and extension of the neural plate by the organizer of Xenopus.

PubMed

Keller, R; Shih, J; Sater, A K; Moreno, C

1992-03-01

This paper demonstrates that convergence and extension within the neural plate of Xenopus laevis are regulated by planar inductive interactions with the adjacent Spemann organizer. The companion article (Keller et al.: Developmental Dynamics 193:199-217, 1992) showed that the prospective hindbrain and spinal cord occupy a very short and very wide area just above the Spemann organizer in the early gastrula and that these regions converge and extend greatly during gastrulation and neurulation, using a sequence of radial and mediolateral cell intercalations. In this article, we show that "planar" contact of these regions with the organizer at their vegetal edge until stage 11 is sufficient to induce convergence and extension, after which their convergence and extension become autonomous. Grafts of the organizer in planar contact with uninduced ectodermal tissues induce these ectodermal tissues to converge and extend by a planar inductive signal from the organizer. Labeling of the inducing or responding tissues confirms that only planar interactions occur. Neural convergence and extension are actually hindered in explants deliberately constructed so that vertical interactions occur. These results show unambiguously that the Spemann organizer induces the extraordinary and precocious convergence and extension movements of the Xenopus neural plate by planar interactions acting over short distances.

Inner ear development: building a spiral ganglion and an organ of Corti out of unspecified ectoderm.

PubMed

Fritzsch, Bernd; Pan, Ning; Jahan, Israt; Elliott, Karen L

2015-07-01

The mammalian inner ear develops from a placodal thickening into a complex labyrinth of ducts with five sensory organs specialized to detect position and movement in space. The mammalian ear also develops a spiraled cochlear duct containing the auditory organ, the organ of Corti (OC), specialized to translate sound into hearing. Development of the OC from a uniform sheet of ectoderm requires unparalleled precision in the topological developmental engineering of four different general cell types, namely sensory neurons, hair cells, supporting cells, and general otic epithelium, into a mosaic of ten distinctly recognizable cell types in and around the OC, each with a unique distribution. Moreover, the OC receives unique innervation by ear-derived spiral ganglion afferents and brainstem-derived motor neurons as efferents and requires neural-crest-derived Schwann cells to form myelin and neural-crest-derived cells to induce the stria vascularis. This transformation of a sheet of cells into a complicated interdigitating set of cells necessitates the orchestrated expression of multiple transcription factors that enable the cellular transformation from ectoderm into neurosensory cells forming the spiral ganglion neurons (SGNs), while simultaneously transforming the flat epithelium into a tube, the cochlear duct, housing the OC. In addition to the cellular and conformational changes forming the cochlear duct with the OC, changes in the surrounding periotic mesenchyme form passageways for sound to stimulate the OC. We review molecular developmental data, generated predominantly in mice, in order to integrate the well-described expression changes of transcription factors and their actions, as revealed in mutants, in the formation of SGNs and OC in the correct position and orientation with suitable innervation. Understanding the molecular basis of these developmental changes leading to the formation of the mammalian OC and highlighting the gaps in our knowledge might guide in vivo attempts to regenerate this most complicated cellular mosaic of the mammalian body for the reconstitution of hearing in a rapidly growing population of aging people suffering from hearing loss.

Conservation of Pax gene expression in ectodermal placodes of the lamprey

NASA Technical Reports Server (NTRS)

McCauley, David W.; Bronner-Fraser, Marianne

2002-01-01

Ectodermal placodes contribute to the cranial ganglia and sense organs of the head and, together with neural crest cells, represent defining features of the vertebrate embryo. The identity of different placodes appears to be specified in part by the expression of different Pax genes, with Pax-3/7 class genes being expressed in the trigeminal placode of mice, chick, frogs and fish, and Pax-2/5/8 class genes expressed in the otic placode. Here, we present the cloning and expression pattern of lamprey Pax-7 and Pax-2, which mark the trigeminal and otic placodes, respectively, as well as other structures characteristic of vertebrate Pax genes. These results suggest conservation of Pax genes and placodal structures in basal and derived vertebrates.

Retinal tear presenting in a patient with ectrodactyly ectodermal dysplasia.

PubMed

Grogg, Jane Ann; Port, Nicholas; Graham, Trevor

2014-04-01

This article aims to report a case of known ectrodactyly ectodermal dysplasia in a young male patient who subsequently was found to have a retinal tear and localized retinal detachment. This is a case report of a 22-year-old white male patient with a history of ectrodactyly ectodermal dysplasia. Our patient initially presented with an acute exacerbation of bilateral, red, irritated eyes. No recent changes in vision were reported. The patient's ocular surface disease was consistent with ectrodermal dysplasia syndrome. However, a dilated fundus examination revealed an asymptomatic retinal tear with a surrounding localized retinal detachment. In this case, the patient presented with longstanding ocular surface disease known to be associated with this patient's inherited ectoderm disorder. In addition, this patient revealed a retinal tear, raising the possibility that patients with inherited congenital ectodermal dysplasia could be at risk for damaged structures originating from the neural ectoderm. In this heterogeneous disease, we are contributing to the existing literature a case of ectodermal dysplasia syndrome with obvious ectodermal complications that also had retinal findings leading us to speculate question if neural ectoderm could also be involved in this inherited disease.

A retrospective study of clinical and mutational findings in 45 Danish families with ectodermal dysplasia.

PubMed

Tiedemann Svendsen, Mathias; Henningsen, Emil; Hertz, Jens Michael; Vestergaard Grejsen, Dorthe; Bygum, Anette

2014-09-01

Ectodermal dysplasias form a complex, nosologic group of diseases with defects in at least 2 ectodermal structures. A retrospective study of patients with ectodermal dysplasia seen at our department over a period of 19 years (1994-2013) was performed. The study population consisted of 67 patients covering 17 different diagnoses. Forty-five families were identified of which 26 were sporadic cases with no affected family members. In 27 tested families a disease-causing mutation was identified in 23 families. Eleven mutations were novel mutations. To our knowledge, we present the first large ectodermal dysplasia cohort focusing on clinical manifestations in combination with mutational analysis. We recommend a nationwide study to estimate the prevalence of the ectodermal dysplasia and to ensure relevant molecular genetic testing which may form the basis of a national ectodermal dysplasia database.

Development of the larval nervous system of the sand dollar, Dendraster excentricus.

PubMed

Burke, R D

1983-01-01

Transformation of the gastrula to the pluteus includes development of the ability of the larva to control the direction of ciliary beat and coordinate activities of the ciliary band with activities of the esophageal muscles (48-60 h, 15 degrees C). Glyoxylic acid-induced fluorescence shows several cells of the animal plate to contain catecholamines in the 36-h gastrula. As the ectoderm thickens to form the ciliary band (36 48 h), the catecholamine-containing cells increase in number and occur dispersed throughout the band. Tissues with the ultrastructural characteristics of nerves first became apparent associated with the ciliary band in 60-h larvae. The coincident development of coordinated behaviour and the appearance of cells with ultrastructural and histochemical characteristics of nerves suggests that the larval nervous system is derived at least in part from cells of the animal plate and develops in association with the ciliary bands.

[Incontinentia pigmenti with defect in cellular immunity].

PubMed

Zamora-Chávez, Antonio; Escobar-Sánchez, Argelia; Sadowinski-Pine, Stanislaw; Saucedo-Ramírez, Omar Josué; Delgado-Barrera, Palmira; Enríquez-Quiñones, Claudia G

Incontinentia pigmenti is a rare, X-linked genetic disease and affects all ectoderm-derived tissues such as skin, appendages, eyes, teeth and central nervous system as well as disorders of varying degree of cellular immunity characterized by decreasing melanin in the epidermis and increase in the dermis. When the condition occurs in males, it is lethal. We present the case of a 2-month-old infant with severe incontinentia pigmenti confirmed by histological examination of skin biopsy. The condition evolved with severe neurological disorders and seizures along with severe cellular immune deficiency, which affected the development of severe infections and caused the death of the patient. The importance of early clinical diagnosis is highlighted along with the importance of multidisciplinary management of neurological disorders and infectious complications. Copyright © 2015 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Fibroblast growth factor receptor 2 (FGFR2) is required for corneal epithelial cell proliferation and differentiation during embryonic development.

PubMed

Zhang, Jinglin; Upadhya, Dinesh; Lu, Lin; Reneker, Lixing W

2015-01-01

Fibroblast growth factors (FGFs) play important roles in many aspects of embryonic development. During eye development, the lens and corneal epithelium are derived from the same surface ectodermal tissue. FGF receptor (FGFR)-signaling is essential for lens cell differentiation and survival, but its role in corneal development has not been fully investigated. In this study, we examined the corneal defects in Fgfr2 conditional knockout mice in which Cre expression is activated at lens induction stage by Pax6 P0 promoter. The cornea in LeCre, Fgfr2(loxP/loxP) mice (referred as Fgfr2(CKO)) was analyzed to assess changes in cell proliferation, differentiation and survival. We found that Fgfr2(CKO) cornea was much thinner in epithelial and stromal layer when compared to WT cornea. At embryonic day 12.5-13.5 (E12.5-13.5) shortly after the lens vesicle detaches from the overlying surface ectoderm, cell proliferation (judged by labeling indices of Ki-67, BrdU and phospho-histone H3) was significantly reduced in corneal epithelium in Fgfr2(CKO) mice. At later stage, cell differentiation markers for corneal epithelium and underlying stromal mesenchyme, keratin-12 and keratocan respectively, were not expressed in Fgfr2(CKO) cornea. Furthermore, Pax6, a transcription factor essential for eye development, was not present in the Fgfr2(CKO) mutant corneal epithelial at E16.5 but was expressed normally at E12.5, suggesting that FGFR2-signaling is required for maintaining Pax6 expression in this tissue. Interestingly, the role of FGFR2 in corneal epithelial development is independent of ERK1/2-signaling. In contrast to the lens, FGFR2 is not required for cell survival in cornea. This study demonstrates for the first time that FGFR2 plays an essential role in controlling cell proliferation and differentiation, and maintaining Pax6 levels in corneal epithelium via ERK-independent pathways during embryonic development.

Mesenchymal Stem Cells – Sources and Clinical Applications

PubMed Central

Klingemann, Hans; Matzilevich, David; Marchand, James

2008-01-01

Summary Although mesenchymal stem cells (MSC) from different tissue sources share many characteristics and generally fulfill accepted criteria for MSC (plastic adherence, certain surface marker expression, and ability to differentiate into mesenchymal tissues), we are increasingly learning that they can be distinguished at the level of cytokine production and gene expression profiles. Their ability to differentiate into different tissues including endodermal and ectodermal lineages, also varies according to tissue origin. Importantly, MSC from fetal sources can undergo more cell divisions before they reach senescence than MSC from adult tissue such as bone marrow or adipose tissue. As we learn more about the differentiation and plasticity of MSC from different sources, health care providers in the future will use them tailored to different medical indications. PMID:21512642

Innexin 3, a New Gene Required for Dorsal Closure in Drosophila Embryo

PubMed Central

Giuliani, Fabrizio; Giuliani, Giuliano; Bauer, Reinhard; Rabouille, Catherine

2013-01-01

Background Dorsal closure is a morphogenetic event that occurs during mid-embryogenesis in many insects including Drosophila, during which the ectoderm migrates on the extraembryonic amnioserosa to seal the embryo dorsally. The contribution of the ectoderm in this event has been known for a long time. However, amnioserosa tension and contractibility have recently been shown also to be instrumental to the closure. A critical pre-requisite for dorsal closure is integrity of these tissues that in part is mediated by cell-cell junctions and cell adhesion. In this regard, mutations impairing junction formation and/or adhesion lead to dorsal closure. However, no role for the gap junction proteins Innexins has so far been described. Results and Discussion Here, we show that Innexin 1, 2 and 3, are present in the ectoderm but also in the amnioserosa in plaques consistent with gap junctions. However, only the loss of Inx3 leads to dorsal closure defects that are completely rescued by overexpression of inx3::GFP in the whole embryo. Loss of Inx3 leads to the destabilisation of Inx1, Inx2 and DE-cadherin at the plasma membrane, suggesting that these four proteins form a complex. Accordingly, in addition to the known interaction of Inx2 with DE-cadherin, we show that Inx3 can bind to DE-cadherin. Furthermore, Inx3-GFP overexpression recruits DE-cadherin from its wildtype plasma membrane domain to typical Innexin plaques, strengthening the notion that they form a complex. Finally, we show that Inx3 stability is directly dependent on tissue tension. Taken together, we propose that Inx3 is a critical factor for dorsal closure and that it mediates the stability of Inx1, 2 and DE-cadherin by forming a complex. PMID:23894431

Identification and characterization of VEGF and FGF from Hydra.

PubMed

Krishnapati, Lakshmi-Surekha; Ghaskadbi, Surendra

2013-01-01

Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) play important roles in the formation of the blood vascular system and in axon guidance, nervous system development and function. Here, we report isolation and characterization of VEGF and FGF homologues from Hydra vulgaris Ind-Pune, a Cnidarian which exhibits an organized nervous system and primitive epithelio-muscular cells. VEGF expression was prominent in the endoderm of the peduncle region and tentacles, as evident from in situ hybridization of whole polyps and its transverse sections. High levels of FGF were detected in the ectoderm of the budding region. The expression of VEGF in endodermal and FGF in interstitial cells was confirmed using sf-1 hydra, a temperature-sensitive mutant strain of Hydra magnipapillata. Tissue-specific expression of VEGF and FGF was confirmed by semi quantitative RT-PCR for ectodermal and endodermal tissues in H. vulgaris Ind-Pune. Treatment with SU5416, a specific inhibitor of the VEGF receptor, did not affect the whole polyp, but did delay both budding and head regeneration, suggesting a possible role of VEGF in nerve cell development, tube formation and/or in branching. FGF expression in the ectoderm of budding region, where the majority of interstitial stem cells reside suggests its role in interstitial stem cell maintenance. Further, activation of canonical Wnt signalling with the glycogen synthase kinase-3β (GSK-3β) inhibitor alsterpaullone caused down-regulation of VEGF and FGF, suggesting an antagonistic relationship between the Wnt and VEGF/FGF pathways. Our results indicate that VEGF and FGF evolved early in evolution, before the development of the blood vascular system, and open up the possibility of elucidating the evolutionarily ancient functions of VEGF and FGF.

Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo

PubMed Central

2010-01-01

Background Pattern formation of the limb skeleton is regulated by a complex interplay of signaling centers located in the ectodermal sheath and mesenchymal core of the limb anlagen, which results, in the forelimb, in the coordinate array of humerus, radius, ulna, carpals, metacarpals and digits. Much less understood is why skeletal elements form only in the central mesenchyme of the limb, whereas muscle anlagen develop in the peripheral mesenchyme ensheathing the chondrogenic center. Classical studies have suggested a role of the limb ectoderm as a negative regulator of limb chondrogenesis. Results In this paper, we investigated the molecular nature of the inhibitory influence of the ectoderm on limb chondrogenesis in the avian embryo in vivo. We show that ectoderm ablation in the early limb bud leads to increased and ectopic expression of early chondrogenic marker genes like Sox9 and Collagen II, indicating that the limb ectoderm inhibits limb chondrogenesis at an early stage of the chondrogenic cascade. To investigate the molecular nature of the inhibitory influence of the ectoderm, we ectopically expressed Wnt6, which is presently the only known Wnt expressed throughout the avian limb ectoderm, and found that Wnt6 overexpression leads to reduced expression of the early chondrogenic marker genes Sox9 and Collagen II. Conclusion Our results suggest that the inhibitory influence of the ectoderm on limb chondrogenesis acts on an early stage of chondrogenesis upsteam of Sox9 and Collagen II. We identify Wnt6 as a candidate mediator of ectodermal chondrogenic inhibition in vivo. We propose a model of Wnt-mediated centripetal patterning of the limb by the surface ectoderm. PMID:20334703

Applications of Microscale Technologies for Regenerative Dentistry

PubMed Central

Hacking, S.A.; Khademhosseini, A.

2009-01-01

While widespread advances in tissue engineering have occurred over the past decade, many challenges remain in the context of tissue engineering and regeneration of the tooth. For example, although tooth development is the result of repeated temporal and spatial interactions between cells of ectoderm and mesoderm origin, most current tooth engineering systems cannot recreate such developmental processes. In this regard, microscale approaches that spatially pattern and support the development of different cell types in close proximity can be used to regulate the cellular microenvironment and, as such, are promising approaches for tooth development. Microscale technologies also present alternatives to conventional tissue engineering approaches in terms of scaffolds and the ability to direct stem cells. Furthermore, microscale techniques can be used to miniaturize many in vitro techniques and to facilitate high-throughput experimentation. In this review, we discuss the emerging microscale technologies for the in vitro evaluation of dental cells, dental tissue engineering, and tooth regeneration. Abbreviations: AS, adult stem cell; BMP, bone morphogenic protein; ECM, extracellular matrix; ES, embryonic stem cell; HA, hydroxyapatite; FGF-2, fibroblast growth factor; iPS, inducible pleuripotent stem cell; IGF-1, insulin-like growth factor; PDGF, platelet-derived growth factor; PDMS, poly(dimethylsiloxane); PGA, polyglycolate; PGS, polyglycerol sebacate; PLGA, poly-L-lactate-co-glycolate; PLL, poly-L-lactate; RGD, Arg-Gly-Asp attachment site; TCP, tricalcium phosphate; TGF-β, transforming growth factor beta; and VEGF, vascular endothelial growth factor. PMID:19493883

Skin symptoms in four ectodermal dysplasia syndromes including two case reports of Rapp-Hodgkin-Syndrome.

PubMed

Knaudt, Björn; Volz, Thomas; Krug, Markus; Burgdorf, Walter; Röcken, Martin; Berneburg, Mark

2012-01-01

The skin, hair and nail changes in four distinct ectodermal dysplasia syndromes are compared and reviewed. These syndromes comprise Christ-Siemens-Touraine syndrome; ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome; ankyloblepharon-ectodermal defects-cleft lip/palate syndrome and Rapp-Hodgkin syndrome. A comprehensive overview of the dermatological signs and symptoms in these syndromes was generated from the database of the Ectodermal Dysplasia Network Germany, the clinical findings in the patients seen in our department and an extensive review of the literature. The findings included abnormalities of skin, sweating, hair and nails. These clinical findings are discussed in relation to the underlying molecular defects known to play a role in these four ectodermal dysplasia syndromes.

Johnson-McMillin syndrome, a neuroectodermal syndrome with conductive hearing loss and microtia: report of a new case.

PubMed

Schweitzer, Daniela N; Yano, Shoji; Earl, Dawn L; Graham, John M

2003-07-30

In 1983, Johnson et al. described 16 related individuals with alopecia, anosmia or hyposmia, conductive hearing loss, microtia and/or atresia of the external auditory canal, and hypogonadotrophic hypogonadism inherited in an autosomal dominant pattern. Other less constant manifestations included facial asymmetry, mental retardation, congenital heart defect, cleft palate, and choanal stenosis. An isolated case was reported later (Johnston et al. [1987: Am J Med Genet 26: 925-927]) and thereafter an affected mother and son (Hennekam and Holtus [1993: Am J Med Genet 47: 714-716]). We describe an additional unrelated female patient with features resembling those of the previously reported cases. She presented with intrauterine growth deficiency, microcephaly, alopecia, bilateral microtia with canal atresia, conductive hearing loss, partial left facial palsy, posterior cleft palate, left choanal stenosis, tetralogy of Fallot, developmental delay, and right thumb polydactyly. Because the phenotypic abnormalities in this syndrome affect the brain, facial structures, ectoderm and its derivatives, outflow tract of the heart, and Rathke's pouch derivatives, this has suggested to previous authors etiologic involvement of the ectoderm and neuroectoderm of the first and second branchial arches, Rathke's pouch, and the diencephalon. Microtia with conductive hearing loss differentiates the condition from other ectodermal dysplasias. In the initial report, females appeared somewhat less affected than males, and there was male-to-male transmission. The mother of our patient manifests subtle features, which suggest she may be a mildly affected female. Additionally, there is a family history of early-onset alopecia in the maternal grandfather's relatives. Copyright 2003 Wiley-Liss, Inc.

Mesomere-derived glutamate decarboxylase-expressing blastocoelar mesenchyme cells of sea urchin larvae

PubMed Central

Katow, Hideki; Katow, Tomoko; Abe, Kouki; Ooka, Shioh; Kiyomoto, Masato; Hamanaka, Gen

2014-01-01

Summary The ontogenetic origin of blastocoelar glutamate decarboxylase (GAD)-expressing cells (GADCs) in larvae of the sea urchin Hemicentrotus pulcherrimus was elucidated. Whole-mount in situ hybridisation (WISH) detected transcription of the gene that encodes GAD in H. pulcherrimus (Hp-gad) in unfertilised eggs and all blastomeres in morulae. However, at and after the swimming blastula stage, the transcript accumulation was particularly prominent in clumps of ectodermal cells throughout the embryonic surface. During the gastrula stage, the transcripts also accumulated in the endomesoderm and certain blastocoelar cells. Consistent with the increasing number of Hp-gad transcribing cells, immunoblot analysis indicated that the relative abundance of Hp-Gad increased considerably from the early gastrula stage until the prism stage. The expression pattern of GADCs determined by immunohistochemistry was identical to the pattern of Hp-gad transcript accumulation determined using WISH. In early gastrulae, GADCs formed blastocoelar cell aggregates around the blastopore with primary mesenchyme cells. The increase in the number of blastocoelar GADCs was inversely proportional to the number of ectodermal GADCs ranging from a few percent of total GADCs in early gastrulae to 80% in late prism larvae; this depended on ingression of ectodermal GADCs into the blastocoel. Some of the blastocoelar GADCs were fluorescein-positive in the larvae that developed from the 16-cell stage chimeric embryos; these comprised fluorescein-labeled mesomeres and unlabelled macromeres and micromeres. Our finding indicates that some of the blastocoelar GADCs are derived from the mesomeres and thus they are the new group of mesenchyme cells, the tertiary mesenchyme cells. PMID:24357228

Differential expression of GSK3β and pS9GSK3β in normal human tissues: can pS9GSK3β be an epithelial marker?

PubMed

Lee, Hojung; Ro, Jae Y

2015-01-01

Glycogen synthase kinase 3β (GSK3β) and phosphorylated GSK3β at Ser9 (pS9GSK3β) are crucial in cellular proliferation and metabolism. GSK3β and pS9GSK3β are deregulated in many diseases including tumors. Data on altered expression of GSK3β and pS9GSK3β are mainly limited to tumor tissues, thus the expression of GSK3β and pS9GSK3β in normal human tissue has been largely unknown. Thus, we examined the immunohistochemical localization of GSK3β and pS9GSK3β in human fetal and adult tissues, and also compared the expression pattern of GSK3β and pS9GSK3β with that of the CK7 and CK20. We found GSK3β expression in neurons of brain, myenteric plexus in gastrointestinal tract, squamous epithelium of skin, and mammary gland. The expression of pS9GSK3β was restricted to the epithelial cells of breast and pancreaticobiliary duct, distal nephron of kidney, gastrointestinal tract, fallopian tube, epididymis, secretory cell of prostatic gland, and umbrella cell of urinary tract. The staining pattern of pS9GSK3β and CK7 was overlapped in most organs except for gastrointestinal tract where CK7 was negative and CK20 was positive. Our results show that the expression of GSK3β may be associated with differentiation of ectodermal derived tissues and pS9GSK3β with that of epithelial cells of endodermal derived tissues in human. In addition, the expression of pS9GSK3β in the selective epithelial cells may indicate its association with secretory or barrier function of specific cells and may serve as another immunohistochemical marker for epithelial cells.

Embryology meets molecular biology: Deciphering the apical ectodermal ridge.

PubMed

Verheyden, Jamie M; Sun, Xin

2017-09-15

More than sixty years ago, while studying feather tracks on the shoulder of the chick embryo, Dr. John Saunders used Nile Blue dye to stain the tissue. There, he noticed a darkly stained line of cells that neatly rims the tip of the growing limb bud. Rather than ignoring this observation, he followed it up by removing this tissue and found that it led to a striking truncation of the limb skeletons. This landmark experiment marks the serendipitous discovery of the apical ectodermal ridge (AER), the quintessential embryonic structure that drives the outgrowth of the limb. Dr. Saunders continued to lead the limb field for the next fifty years, not just through his own work, but also by inspiring the next generation of researchers through his infectious love of science. Together, he and those who followed ushered in the discovery of fibroblast growth factor (FGF) as the AER molecule. The seamless marriage of embryology and molecular biology that led to the decoding of the AER serves as a shining example of how discoveries are made for the rest of the developmental biology field. Copyright © 2017 Elsevier Inc. All rights reserved.

Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

PubMed Central

Landry, Joseph; Sharov, Alexei A.; Piao, Yulan; Sharova, Lioudmila V.; Xiao, Hua; Southon, Eileen; Matta, Jennifer; Tessarollo, Lino; Zhang, Ying E.; Ko, Minoru S. H.; Kuehn, Michael R.; Yamaguchi, Terry P.; Wu, Carl

2008-01-01

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo. PMID:18974875

A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene

PubMed Central

2011-01-01

Background Hypohidrotic ectodermal dysplasia (HED) is a congenital disorder characterized by sparse hair, oligodontia, and inability to sweat. It is caused by mutations in any of three Eda pathway genes: ectodysplasin (Eda), Eda receptor (Edar), and Edar-associated death domain (Edaradd), which encode ligand, receptor, and intracellular adaptor molecule, respectively. The Eda signaling pathway activates NF-κB, which is central to ectodermal differentiation. Although the causative genes and the molecular pathway affecting HED have been identified, no curative treatment for HED has been established. Previously, we found a rat spontaneous mutation that caused defects in hair follicles and named it sparse-and-wavy (swh). Here, we have established the swh rat as the first rat model of HED and successfully identified the swh mutation. Results The swh/swh rat showed sparse hair, abnormal morphology of teeth, and absence of sweat glands. The ectoderm-derived glands, meibomian, preputial, and tongue glands, were absent. We mapped the swh mutation to the most telomeric part of rat Chr 7 and found a Pro153Ser missense mutation in the Edaradd gene. This mutation was located in the death domain of EDARADD, which is crucial for signal transduction and resulted in failure to activate NF-κB. Conclusions These findings suggest that swh is a loss-of-function mutation in the rat Edaradd and indicate that the swh/swh rat would be an excellent animal model of HED that could be used to investigate the pathological basis of the disease and the development of new therapies. PMID:22013926

ECTODERMAL WNT/β-CATENIN SIGNALING SHAPES THE MOUSE FACE

PubMed Central

Reid, Bethany S.; Yang, Hui; Melvin, Vida Senkus; Taketo, Makoto M.; Williams, Trevor

2010-01-01

The canonical Wnt/β-catenin pathway is an essential component of multiple developmental processes. To investigate the role of this pathway in the ectoderm during facial morphogenesis, we generated conditional β-catenin mouse mutants using a novel ectoderm-specific Cre recombinase transgenic line. Our results demonstrate that ablating or stabilizing β-catenin in the embryonic ectoderm causes dramatic changes in facial morphology. There are accompanying alterations in the expression of Fgf8 and Shh, key molecules that establish a signaling center critical for facial patterning, the frontonasal ectodermal zone (FEZ). These data indicate that Wnt/β-catenin signaling within the ectoderm is critical for facial development and further suggest that this pathway is an important mechanism for generating the diverse facial shapes of vertebrates during evolution. PMID:21087601

Prosthodontic management of a patient with ectodermal dysplasia.

PubMed

Nandini, Yamini

2013-12-01

Ectodermal dysplasia is a rare congenital disease that affects the ectodermal structures. It is characterized by hypotrichosis, hypohidrosis and hypodontia. A 14-year-old boy with ectodermal dysplasia presenting with oligodontia and marked resorption of the maxillary and mandibular alveolar ridges is reported. Prosthetic rehabilitation in the form of a maxillary and mandibular partial denture was made with metal crowns on existing lower teeth to achieve appropriate vertical dimension. Significant improvement in speech, masticatory function and facial esthetics was achieved. Removable prosthodontics can provide an acceptable solution to esthetic, functional and psychological rehabilitation in patients with ectodermal dysplasia.

Overdenture restoration in a growing patient with hypohidrotic ectodermal dysplasia: a clinical report.

PubMed

Pae, Ahran; Kim, Kyu; Kim, Hyeong-Seob; Kwon, Kung-Rock

2011-03-01

Ectodermal dysplasia is a hereditary disorder of ectodermal origin. A 12-year-old boy was referred for management of the oral manifestations of his ectodermal dysplasia. An overdenture retained by natural teeth for the maxilla and a double-crown-retained denture for the mandible were made. Double-crown-retained dentures may be modified into complete dentures if the abutment teeth are lost. The patient was instructed to maintain oral hygiene and return periodically for follow-up visits. This report describes a potential routine approach to restoring the appearance, function, and psyche of a growing boy with ectodermal dysplasia.

Aorta-derived mesoangioblasts differentiate into the oligodendrocytes by inhibition of the Rho kinase signaling pathway.

PubMed

Wang, Lei; Kamath, Anant; Frye, Janie; Iwamoto, Gary A; Chun, Ju Lan; Berry, Suzanne E

2012-05-01

Mesoangioblasts are vessel-derived stem cells that differentiate into mesodermal derivatives. We have isolated postnatal aorta-derived mesoangioblasts (ADMs) that differentiate into smooth, skeletal, and cardiac muscle, and adipocytes, and regenerate damaged skeletal muscle in a murine model for Duchenne muscular dystrophy. We report that the marker profile of ADM is similar to that of mesoangioblasts isolated from embryonic dorsal aorta, postnatal bone marrow, and heart, but distinct from mesoangioblasts derived from skeletal muscle. We also demonstrate that ADM differentiate into myelinating glial cells. ADM localize to peripheral nerve bundles in regenerating muscles and exhibit morphology and marker expression of mature Schwann cells, and myelinate axons. In vitro, ADM spontaneously express markers of oligodendrocyte progenitors, including the chondroitin sulphate proteoglycan NG2, nestin, platelet-derived growth factor (PDGF) receptor α, the A2B5 antigen, thyroid hormone nuclear receptor α, and O4. Pharmacological inhibition of Rho kinase (ROCK) initiated process extension by ADM, and when combined with insulin-like growth factor 1, PDGF, and thyroid hormone, enhanced ADM expression of oligodendrocyte precursor markers and maturation into the oligodendrocyte lineage. ADM injected into the right lateral ventricle of the brain migrate to the corpus callosum, and cerebellar white matter, where they express components of myelin. Because ADM differentiate or mature into cell types of both mesodermal and ectodermal origin, they may be useful for treatment of a variety of degenerative diseases, or repair and regeneration of multiple cell types in severely damaged tissue.

ORAI1 mutations abolishing store-operated Ca2+ entry cause anhidrotic ectodermal dysplasia with immunodeficiency.

PubMed

Lian, Jayson; Cuk, Mario; Kahlfuss, Sascha; Kozhaya, Lina; Vaeth, Martin; Rieux-Laucat, Frédéric; Picard, Capucine; Benson, Melina J; Jakovcevic, Antonia; Bilic, Karmen; Martinac, Iva; Stathopulos, Peter; Kacskovics, Imre; Vraetz, Thomas; Speckmann, Carsten; Ehl, Stephan; Issekutz, Thomas; Unutmaz, Derya; Feske, Stefan

2017-11-16

Store-operated Ca 2+ entry (SOCE) through Ca 2+ release-activated Ca 2+ channels is an essential signaling pathway in many cell types. Ca 2+ release-activated Ca 2+ channels are formed by ORAI1, ORAI2, and ORAI3 proteins and activated by stromal interaction molecule (STIM) 1 and STIM2. Mutations in the ORAI1 and STIM1 genes that abolish SOCE cause a combined immunodeficiency (CID) syndrome that is accompanied by autoimmunity and nonimmunologic symptoms. We performed molecular and immunologic analysis of patients with CID, anhidrosis, and ectodermal dysplasia of unknown etiology. We performed DNA sequencing of the ORAI1 gene, modeling of mutations on ORAI1 crystal structure, analysis of ORAI1 mRNA and protein expression, SOCE measurements, immunologic analysis of peripheral blood lymphocyte populations by using flow cytometry, and histologic and ultrastructural analysis of patient tissues. We identified 3 novel autosomal recessive mutations in ORAI1 in unrelated kindreds with CID, autoimmunity, ectodermal dysplasia with anhidrosis, and muscular dysplasia. The patients were homozygous for p.V181SfsX8, p.L194P, and p.G98R mutations in the ORAI1 gene that suppressed ORAI1 protein expression and SOCE in the patients' lymphocytes and fibroblasts. In addition to impaired T-cell cytokine production, ORAI1 mutations were associated with strongly reduced numbers of invariant natural killer T and regulatory T (Treg) cells and altered composition of γδ T-cell and natural killer cell subsets. ORAI1 null mutations are associated with reduced numbers of invariant natural killer T and Treg cells that likely contribute to the patients' immunodeficiency and autoimmunity. ORAI1-deficient patients have dental enamel defects and anhidrosis, representing a new form of anhidrotic ectodermal dysplasia with immunodeficiency that is distinct from previously reported patients with anhidrotic ectodermal dysplasia with immunodeficiency caused by mutations in the nuclear factor κB signaling pathway (IKBKG and NFKBIA). Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Ectoderm exerts the driving force for gastrulation in the sand dollar Scaphechinus mirabilis.

PubMed

Takata, H; Kominami, T

2001-06-01

How the ectodermal layer relates to the invagination processes was examined in the sand dollar Scaphechinus mirabilis. When the turgor pressure of blastocoele was increased, invagination was completely blocked. In contrast, an increase in turgor pressure did not affect elongation of the gut rudiment in the regular echinoid Hemicentrotus pulcherrimus. Rhodamine-phalloidin staining showed that the distribution of actin filaments was different between two species of embryos. In S. mirabilis gastrulating embryos, abundant actin filaments were seen at the basal cortex of ectoderm in addition to archenteron cells, while the intense signal was restricted to the archenteron in H. pulcherrimus. To investigate whether actin filaments contained in the ectodermal layer exert the force of invagination, a small part of the ectodermal layer was aspirated with a micropipette. If S. mirabilis embryos were aspirated from the onset of gastrulation, invagination did not occur at all, irrespective of the suction site. Even after the archenteron had invaginated to one-half of its full length, further elongation of the archenteron was severely blocked by suction of the lateral ectoderm. In contrast, suction of the ectodermal layer did not affect the elongation processes in H. pulcherrimus. These results strongly suggest that the ectodermal layer, especially in the vegetal half, exerts the driving force of invagination in S. mirabilis.

Mutation of KREMEN1, a modulator of Wnt signaling, is responsible for ectodermal dysplasia including oligodontia in Palestinian families.

PubMed

Issa, Yasmin A; Kamal, Lara; Rayyan, Amal Abu; Dweik, Dima; Pierce, Sarah; Lee, Ming K; King, Mary-Claire; Walsh, Tom; Kanaan, Moien

2016-10-01

Tooth development is controlled by the same processes that regulate formation of other ectodermal structures. Mutations in the genes underlying these processes may cause ectodermal dysplasia, including severe absence of primary or permanent teeth. Four consanguineous Palestinian families presented with oligodontia and hair and skin features of ectodermal dysplasia. Appearance of ectodermal dysplasia was consistent with autosomal recessive inheritance. Exome sequencing followed by genotyping of 56 informative relatives in the 4 families suggests that the phenotype is due to homozygosity for KREMEN1 p.F209S (c.626 T>C) on chromosome 22 at g.29,521,399 (hg19). The variant occurs in the highly conserved extracellular WSC domain of KREMEN1, which is known to be a high affinity receptor of Dickkopf-1, a component of the Dickkopf-Kremen-LRP6 complex, and a potent regulator of Wnt signaling. The Wnt signaling pathway is critical to development of ectodermal structures. Mutations in WNT10A, LRP6, EDA, and other genes in this pathway lead to tooth agenesis with or without other ectodermal anomalies. Our results implicate KREMEN1 for the first time in a human disorder and provide additional details on the role of the Wnt signaling in ectodermal and dental development.

Hypohidrotic ectodermal dysplasia: a felicitous approach to esthetic and prosthetic management.

PubMed

Singh, Tapan; Singh, Ronauk; Singh, Gurendra Pal; Singh, Jitender Pal

2013-05-01

Ectodermal dysplasia is a hereditary disease characterized by congenital dysplasia of one or more ectodermal structure and other accessory appendages. The oral manifestations are anodontia and poor bony foundation which impairs both esthetic as well as the masticatory function. The prosthodontic management of patients with such dysplastic condition necessitates a multidisciplinary approach. This case report describes the prosthodontic oral rehabilitation of a 16 years old female pediatric patient with ectodermal dysplasia. How to cite this article: Singh T, Singh R, Singh GP, Singh JP. Hypohidrotic Ectodermal Dysplasia: A Felicitous Approach to Esthetic and Prosthetic Management. Int J Clin Pediatr Dent 2013;6(2):140-145.

Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos

PubMed Central

Krupke, Oliver A; Zysk, Ivona; Mellott, Dan O; Burke, Robert D

2016-01-01

The mechanisms that underlie directional cell migration are incompletely understood. Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin. In sea urchin embryos, pigmented immunocytes are specified in vegetal epithelium, transition to mesenchyme, migrate, and re-enter ectoderm, distributing in dorsal ectoderm and ciliary band, but not ventral ectoderm. Immunocytes express Sp-Eph and Sp-Efn is expressed throughout dorsal and ciliary band ectoderm. Interfering with expression or function of Sp-Eph results in rounded immunocytes entering ectoderm but not adopting a dendritic form. Expressing Sp-Efn throughout embryos permits immunocyte insertion in ventral ectoderm. In mosaic embryos, immunocytes insert preferentially in ectoderm expressing Sp-Efn. We conclude that Sp-Eph signaling is necessary and sufficient for epithelial insertion. As well, we propose that immunocytes disperse when Sp-Eph enhances adhesion, causing haptotactic movement to regions of higher ligand abundance. This is a distinctive example of Eph/Ephrin signaling acting positively to pattern migrating cells. DOI: http://dx.doi.org/10.7554/eLife.16000.001 PMID:27474796

Inner ear development: Building a spiral ganglion and an organ of Corti out of unspecified ectoderm

PubMed Central

Fritzsch, Bernd; Pan, Ning; Jahan, Israt; Elliott, Karen L.

2014-01-01

The mammalian inner ear develops from a placodal thickening into a complex labyrinth of ducts with five sensory organs specialized to detect position and movement in space. In addition, the mammalian ear develops a spiraled cochlear duct containing the auditory organ, the organ of Corti (OC), specialized to translate sound into hearing. Developing the OC out of a uniform sheet of ectoderm requires an unparalleled precision in topological developmental engineering of four different general cell types, sensory neurons, hair cells, supporting cells, and general otic epithelium, into a mosaic of ten distinctly recognizable cell types in and around the OC, each with a unique distribution. In addition, the OC receives a unique innervation by ear-derived spiral ganglion afferents and brainstem-derived motor neurons as efferents, and requires neural crest-derived Schwann cells to form myelin and neural crest-derived cells to induce the stria vascularis. To achieve this transformation of a sheet of cells into a complicated interdigitating set of cells necessitates the orchestrated expression of multiple transcription factors that enable the cellular transformation from ectoderm into neurosensory cells forming the spiral ganglion neurons (SGN) while simultaneously transforming the flat epithelium into a tube, the cochlear duct housing the OC. In addition to the cellular and conformational changes to make the cochlear duct with the OC, additional changes in the surrounding periotic mesenchyme form passageways for sound to stimulate the OC. This article reviews molecular developmental data generated predominantly in mice. The available data are ordered into a plausible scenario that integrates the well described expression changes of transcription factors and their actions revealed in mouse mutants for formation of SGNs and OC in the right position and orientation with the right kind of innervation. Understanding the molecular basis of these developmental changes leading to the formation of the mammalian OC and highlighting the gaps in our knowledge may guide in vivo attempts to regenerate this most complicated cellular mosaic of the mammalian body to reconstitute hearing in a rapidly growing population of aging people suffering from hearing loss. PMID:25381571

BK virus encephalopathy and sclerosing vasculopathy in a patient with hypohidrotic ectodermal dysplasia and immunodeficiency.

PubMed

Darbinyan, Armine; Major, Eugene O; Morgello, Susan; Holland, Steven; Ryschkewitsch, Caroline; Monaco, Maria Chiara; Naidich, Thomas P; Bederson, Joshua; Malaczynska, Joanna; Ye, Fei; Gordon, Ronald; Cunningham-Rundles, Charlotte; Fowkes, Mary; Tsankova, Nadejda M

2016-07-13

Human BK polyomavirus (BKV) is reactivated under conditions of immunosuppression leading most commonly to nephropathy or cystitis; its tropism for the brain is rare and poorly understood. We present a unique case of BKV-associated encephalopathy in a man with hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID) due to IKK-gamma (NEMO) mutation, who developed progressive neurological symptoms. Brain biopsy demonstrated polyomavirus infection of gray and white matter, with predominant involvement of cortex and distinct neuronal tropism, in addition to limited demyelination and oligodendroglial inclusions. Immunohistochemistry demonstrated polyoma T-antigen in neurons and glia, but expression of VP1 capsid protein only in glia. PCR analysis on both brain biopsy tissue and cerebrospinal fluid detected high levels of BKV DNA. Sequencing studies further identified novel BKV variant and disclosed unique rearrangements in the noncoding control region of the viral DNA (BKVN NCCR). Neuropathological analysis also demonstrated an unusual form of obliterative fibrosing vasculopathy in the subcortical white matter with abnormal lysosomal accumulations, possibly related to the patient's underlying ectodermal dysplasia. Our report provides the first neuropathological description of HED-ID due to NEMO mutation, and expands the diversity of neurological presentations of BKV infection in brain, underscoring the importance of its consideration in immunodeficient patients with unexplained encephalopathy. We also document novel BKVN NCCR rearrangements that may be associated with the unique neuronal tropism in this patient.

Hereditary hypohidrotic ectodermal dysplasia: report of a rare case.

PubMed

Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

2013-09-01

Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition.

Hereditary Hypohidrotic Ectodermal Dysplasia: Report of a Rare Case

PubMed Central

Paramkusam, Geetha; Meduri, Venkateswarlu; Nadendla, Lakshmi Kavitha; Shetty, Namratha

2013-01-01

Hereditary Hypohidrotic Ectodermal Dysplasia (HHED), an X-linked, recessive, Mendelian character, is seen usually in males and it is inherited through female carriers. It is characterised by congenital dysplasia of one or more ectodermal structures and it is manifested by hypohidrosis, hypotrichosis and hypodontia. It results from abnormal morphogenesis of cutaneous and oral embryonic ectoderm. Here, we are presenting a rare case of HHED in a 19 year female with classic features of this condition. PMID:24179947

Ectodermal dysplasia: otolaryngologic evaluation of 23 cases.

PubMed

Yildirim, Muzeyyen; Yorgancilar, Ediz; Gun, Ramazan; Topcu, Ismail

2012-02-01

The aim of this prospective study was to improve the quality of life of and reduce morbidity for patients with ectodermal dysplasia by assessing their actual and potential ENT pathologies, and offering methods of prevention and treatment. The study was conducted between 2006 and 2008 and included 23 patients diagnosed with ectodermal dysplasia. The major symptoms of ectodermal dysplasia were evaluated. Patient histories were obtained in all cases, and a complete head and neck examination was carried out. Of the 23 patients (11 males and 12 females, aged 5 to 45 years) diagnosed with ectodermal dysplasia, 22 had hypohidrotic ectodermal dysplasia and 1 had ectrodactyly-ectodermal dysplasia-clefting syndrome. In all patients diagnosed with hypohidrotic ectodermal dysplasia, the salivary glands were examined by ultrasonography and, when necessary, by scintigraphy. Hearing defects in patients with otologic problems were determined by audiometric examination: 39.1% of the patients had hearing loss, 43.5% had otitis media, and 39.1% had impacted cerumen. The most common rhinologic findings were saddle nose deformity in 56.5%, nasal obstruction and nasal dryness (52.2% each), and chronic rhinitis/rhinosinusitis (34.8%). The most common oral and oropharyngeal findings were difficulty chewing in 82.6% and dry mouth in 78.3%. All 23 patients had required dental work. Because this disorder affects several aspects of the body, its treatment requires a multidisciplinary approach, with the otolaryngologist being a vital part of the management team.

Mouth development.

PubMed

Chen, Justin; Jacox, Laura A; Saldanha, Francesca; Sive, Hazel

2017-09-01

A mouth is present in all animals, and comprises an opening from the outside into the oral cavity and the beginnings of the digestive tract to allow eating. This review focuses on the earliest steps in mouth formation. In the first half, we conclude that the mouth arose once during evolution. In all animals, the mouth forms from ectoderm and endoderm. A direct association of oral ectoderm and digestive endoderm is present even in triploblastic animals, and in chordates, this region is known as the extreme anterior domain (EAD). Further support for a single origin of the mouth is a conserved set of genes that form a 'mouth gene program' including foxA and otx2. In the second half of this review, we discuss steps involved in vertebrate mouth formation, using the frog Xenopus as a model. The vertebrate mouth derives from oral ectoderm from the anterior neural ridge, pharyngeal endoderm and cranial neural crest (NC). Vertebrates form a mouth by breaking through the body covering in a precise sequence including specification of EAD ectoderm and endoderm as well as NC, formation of a 'pre-mouth array,' basement membrane dissolution, stomodeum formation, and buccopharyngeal membrane perforation. In Xenopus, the EAD is also a craniofacial organizer that guides NC, while reciprocally, the NC signals to the EAD to elicit its morphogenesis into a pre-mouth array. Human mouth anomalies are prevalent and are affected by genetic and environmental factors, with understanding guided in part by use of animal models. WIREs Dev Biol 2017, 6:e275. doi: 10.1002/wdev.275 For further resources related to this article, please visit the WIREs website. © 2017 The Authors. WIREs Developmental Biology published by Wiley Periodicals, Inc.

Lineage specific expression of Polycomb Group Proteins in human embryonic stem cells in vitro.

PubMed

Pethe, Prasad; Pursani, Varsha; Bhartiya, Deepa

2015-05-01

Human embryonic (hES) stem cells are an excellent model to study lineage specification and differentiation into various cell types. Differentiation necessitates repression of specific genes not required for a particular lineage. Polycomb Group (PcG) proteins are key histone modifiers, whose primary function is gene repression. PcG proteins form complexes called Polycomb Repressive Complexes (PRCs), which catalyze histone modifications such as H2AK119ub1, H3K27me3, and H3K9me3. PcG proteins play a crucial role during differentiation of stem cells. The expression of PcG transcripts during differentiation of hES cells into endoderm, mesoderm, and ectoderm lineage is yet to be shown. In-house derived hES cell line KIND1 was differentiated into endoderm, mesoderm, and ectoderm lineages; followed by characterization using RT-PCR for HNF4A, CDX2, MEF2C, TBX5, SOX1, and MAP2. qRT-PCR and western blotting was performed to compare expression of PcG transcripts and proteins across all the three lineages. We observed that cells differentiated into endoderm showed upregulation of RING1B, BMI1, EZH2, and EED transcripts. Mesoderm differentiation was characterized by significant downregulation of all PcG transcripts during later stages. BMI1 and RING1B were upregulated while EZH2, SUZ12, and EED remained low during ectoderm differentiation. Western blotting also showed distinct expression of BMI1 and EZH2 during differentiation into three germ layers. Our study shows that hES cells differentiating into endoderm, mesoderm, and ectoderm lineages show distinct PcG expression profile at transcript and protein level. © 2015 International Federation for Cell Biology.

Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.

PubMed

Berko, Esther R; Suzuki, Masako; Beren, Faygel; Lemetre, Christophe; Alaimo, Christine M; Calder, R Brent; Ballaban-Gil, Karen; Gounder, Batya; Kampf, Kaylee; Kirschen, Jill; Maqbool, Shahina B; Momin, Zeineen; Reynolds, David M; Russo, Natalie; Shulman, Lisa; Stasiek, Edyta; Tozour, Jessica; Valicenti-McDermott, Maria; Wang, Shenglong; Abrahams, Brett S; Hargitai, Joseph; Inbar, Dov; Zhang, Zhengdong; Buxbaum, Joseph D; Molholm, Sophie; Foxe, John J; Marion, Robert W; Auton, Adam; Greally, John M

2014-01-01

DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

In vivo imaging of coral tissue and skeleton with optical coherence tomography

PubMed Central

Wentzel, Camilla; Jacques, Steven L.; Wagner, Michael

2017-01-01

Application of optical coherence tomography (OCT) for in vivo imaging of tissue and skeleton structure of intact living corals enabled the non-invasive visualization of coral tissue layers (endoderm versus ectoderm), skeletal cavities and special structures such as mesenterial filaments and mucus release from intact living corals. Coral host chromatophores containing green fluorescent protein-like pigment granules appeared hyper-reflective to near-infrared radiation allowing for excellent optical contrast in OCT and a rapid characterization of chromatophore size, distribution and abundance. In vivo tissue plasticity could be quantified by the linear contraction velocity of coral tissues upon illumination resulting in dynamic changes in the live coral tissue surface area, which varied by a factor of 2 between the contracted and expanded state of a coral. Our study provides a novel view on the in vivo organization of coral tissue and skeleton and highlights the importance of microstructural dynamics for coral ecophysiology. PMID:28250104

Plakophilin-3 Is Required for Late Embryonic Amphibian Development, Exhibiting Roles in Ectodermal and Neural Tissues

PubMed Central

Munoz, William A.; Kloc, Malgorzata; Hofmann, Ilse; Sater, Amy; Vleminckx, Kris; McCrea, Pierre D.

2012-01-01

The p120-catenin family has undergone a significant expansion during the evolution of vertebrates, resulting in varied functions that have yet to be discerned or fully characterized. Likewise, members of the plakophilins, a related catenin subfamily, are found throughout the cell with little known about their functions outside the desmosomal plaque. While the plakophilin-3 (Pkp3) knockout mouse resulted in skin defects, we find larger, including lethal effects following its depletion in Xenopus. Pkp3, unlike some other characterized catenins in amphibians, does not have significant maternal deposits of mRNA. However, during embryogenesis, two Pkp3 protein products whose temporal expression is partially complimentary become expressed. Only the smaller of these products is found in adult Xenopus tissues, with an expression pattern exhibiting distinctions as well as overlaps with those observed in mammalian studies. We determined that Xenopus Pkp3 depletion causes a skin fragility phenotype in keeping with the mouse knockout, but more novel, Xenopus tailbud embryos are hyposensitive to touch even in embryos lacking outward discernable phenotypes, and we additionally resolved disruptions in certain peripheral neural structures, altered establishment and migration of neural crest, and defects in ectodermal multiciliated cells. The use of two distinct morpholinos, as well as rescue approaches, indicated the specificity of these effects. Our results point to the requirement of Pkp3 in amphibian embryogenesis, with functional roles in a number of tissue types. PMID:22496792

Bud detachment in hydra requires activation of fibroblast growth factor receptor and a Rho–ROCK–myosin II signaling pathway to ensure formation of a basal constriction

PubMed Central

Holz, Oliver; Apel, David; Steinmetz, Patrick; Lange, Ellen; Hopfenmüller, Simon; Ohler, Kerstin; Sudhop, Stefanie

2017-01-01

Background: Hydra propagates asexually by exporting tissue into a bud, which detaches 4 days later as a fully differentiated young polyp. Prerequisite for detachment is activation of fibroblast growth factor receptor (FGFR) signaling. The mechanism which enables constriction and tissue separation within the monolayered ecto‐ and endodermal epithelia is unknown. Results: Histological sections and staining of F‐actin by phalloidin revealed conspicuous cell shape changes at the bud detachment site indicating a localized generation of mechanical forces and the potential enhancement of secretory functions in ectodermal cells. By gene expression analysis and pharmacological inhibition, we identified a candidate signaling pathway through Rho, ROCK, and myosin II, which controls bud base constriction and rearrangement of the actin cytoskeleton. Specific regional myosin phosphorylation suggests a crucial role of ectodermal cells at the detachment site. Inhibition of FGFR, Rho, ROCK, or myosin II kinase activity is permissive for budding, but represses myosin phosphorylation, rearrangement of F‐actin and constriction. The young polyp remains permanently connected to the parent by a broad tissue bridge. Conclusions: Our data suggest an essential role of FGFR and a Rho‐ROCK‐myosin II pathway in the control of cell shape changes required for bud detachment. Developmental Dynamics 246:502–516, 2017. © 2017 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists PMID:28411398

Bud detachment in hydra requires activation of fibroblast growth factor receptor and a Rho-ROCK-myosin II signaling pathway to ensure formation of a basal constriction.

PubMed

Holz, Oliver; Apel, David; Steinmetz, Patrick; Lange, Ellen; Hopfenmüller, Simon; Ohler, Kerstin; Sudhop, Stefanie; Hassel, Monika

2017-07-01

Hydra propagates asexually by exporting tissue into a bud, which detaches 4 days later as a fully differentiated young polyp. Prerequisite for detachment is activation of fibroblast growth factor receptor (FGFR) signaling. The mechanism which enables constriction and tissue separation within the monolayered ecto- and endodermal epithelia is unknown. Histological sections and staining of F-actin by phalloidin revealed conspicuous cell shape changes at the bud detachment site indicating a localized generation of mechanical forces and the potential enhancement of secretory functions in ectodermal cells. By gene expression analysis and pharmacological inhibition, we identified a candidate signaling pathway through Rho, ROCK, and myosin II, which controls bud base constriction and rearrangement of the actin cytoskeleton. Specific regional myosin phosphorylation suggests a crucial role of ectodermal cells at the detachment site. Inhibition of FGFR, Rho, ROCK, or myosin II kinase activity is permissive for budding, but represses myosin phosphorylation, rearrangement of F-actin and constriction. The young polyp remains permanently connected to the parent by a broad tissue bridge. Our data suggest an essential role of FGFR and a Rho-ROCK-myosin II pathway in the control of cell shape changes required for bud detachment. Developmental Dynamics 246:502-516, 2017. © 2017 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. © 2017 The Authors Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.

PubMed

Liu, Ming; Zhao, Shuangyun; Lin, Qingjie; Wang, Xiu-Ping

2015-04-01

Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saito, Kayoko; Ikeya, Kiyoko; Kondo, Eri

Mosaicism is a mixed state, with two cell populations of different genetic origins caused by a cell mutation occurring after fertilization. In the present case, DNA analysis of lymphocytes led to a DMD diagnosis before death. Postmortem immunocytochemical and DNA analysis showed somatic mosaicism. At age 18 years, blood lymphocyte DNA analysis showed a DMD gene deletion, upstream from exon 7 to the 5{prime} end containing both muscle and brain promoters. As the patient`s mother and elder sister had no deletions, he was considered to have a new mutation. Immunocytochemical studies of postmortem tissues showed that dystrophin was absent frommore » the tongue, deltoid, intercostal, psoas and rectus femoris muscles, but there was a mix of dystrophin-positive and negative fibers in the rectus abdominis, cardiac, temporalis and sternocleidomastoid muscles. All diaphragm cells were dystrophin positive. Polymerase chain reaction (PCR) amplification from all tissues except the temporalis and sternocleidomastoid muscles, diaphragm and kidney, in which no deletion was found, showed the deletion from at least exon 6 to the 5{prime} end containing both muscle and brain promoters. In this case, a genomic deletion of the DMD gene contributed to the formation of tissues derived from both ectoderm and endoderm, and cells of mesodermal origin showed genotypic and phenotypic heterogeneity. Our results indicate a mutation of the present case may have occurred just before the period of germ layer formation. 34 refs., 7 figs.« less

Dental pulp of the third molar: a new source of pluripotent-like stem cells.

PubMed

Atari, Maher; Gil-Recio, Carlos; Fabregat, Marc; García-Fernández, Dani; Barajas, Miguel; Carrasco, Miguel A; Jung, Han-Sung; Alfaro, F Hernández; Casals, Nuria; Prosper, Felipe; Ferrés-Padró, Eduard; Giner, Luis

2012-07-15

Dental pulp is particularly interesting in regenerative medicine because of the accessibility and differentiation potential of the tissue. Dental pulp has an early developmental origin with multi-lineage differentiation potential as a result of its development during childhood and adolescence. However, no study has previously identified the presence of stem cell populations with embryonic-like phenotypes in human dental pulp from the third molar. In the present work, we describe a new population of dental pulp pluripotent-like stem cells (DPPSCs) that were isolated by culture in medium containing LIF, EGF and PDGF. These cells are SSEA4(+), OCT3/4(+), NANOG(+), SOX2(+), LIN28(+), CD13(+), CD105(+), CD34(-), CD45(-), CD90(+), CD29(+), CD73(+), STRO1(+) and CD146(-), and they show genetic stability in vitro based on genomic analysis with a newly described CGH technique. Interestingly, DPPSCs were able to form both embryoid-body-like structures (EBs) in vitro and teratoma-like structures that contained tissues derived from all three embryonic germ layers when injected in nude mice. We examined the capacity of DPPSCs to differentiate in vitro into tissues that have similar characteristics to mesoderm, endoderm and ectoderm layers in both 2D and 3D cultures. We performed a comparative RT-PCR analysis of GATA4, GATA6, MIXL1, NANOG, OCT3/4, SOX1 and SOX2 to determine the degree of similarity between DPPSCs, EBs and human induced pluripotent stem cells (hIPSCs). Our analysis revealed that DPPSCs, hIPSC and EBs have the same gene expression profile. Because DPPSCs can be derived from healthy human molars from patients of different sexes and ages, they represent an easily accessible source of stem cells, which opens a range of new possibilities for regenerative medicine.

Molluscan engrailed expression, serial organization, and shell evolution

NASA Technical Reports Server (NTRS)

Jacobs, D. K.; Wray, C. G.; Wedeen, C. J.; Kostriken, R.; DeSalle, R.; Staton, J. L.; Gates, R. D.; Lindberg, D. R.

2000-01-01

Whether the serial features found in some molluscs are ancestral or derived is considered controversial. Here, in situ hybridization and antibody studies show iterated engrailed-gene expression in transverse rows of ectodermal cells bounding plate field development and spicule formation in the chiton, Lepidochitona cavema, as well as in cells surrounding the valves and in the early development of the shell hinge in the clam, Transennella tantilla. Ectodermal expression of engrailed is associated with skeletogenesis across a range of bilaterian phyla, suggesting a single evolutionary origin of invertebrate skeletons. The shared ancestry of bilaterian-invertebrate skeletons may help explain the sudden appearance of shelly fossils in the Cambrian. Our interpretation departs from the consideration of canonical metameres or segments as units of evolutionary analysis. In this interpretation, the shared ancestry of engrailed-gene function in the terminal/posterior addition of serially repeated elements during development explains the iterative expression of engrailed genes in a range of metazoan body plans.

Ectrodactyly-ectodermal dysplasia-cleft lip and palate syndrome.

PubMed

Dhar, Reema Sharma; Bora, Amitava

2014-01-01

Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome is an autosomal dominant disorder characterized by the triad of ectrodactyly-ectodermal dysplasia, and facial clefting along with some associated features. Presence of all the three major features in a single individual is extremely rare. We report a case of 4 year 11 months old child with EEC syndrome having ectodermal dysplasia-cleft lip and cleft palate and ectrodactyly with some associated features. Clinical features, diagnosis and role of a dentist in the multidisciplinary treatment approach have been elaborated in this case report.

A gonad-expressed opsin mediates light-induced spawning in the jellyfish Clytia

PubMed Central

Quiroga Artigas, Gonzalo; Lapébie, Pascal; Leclère, Lucas; Takeda, Noriyo; Deguchi, Ryusaku; Jékely, Gáspár

2018-01-01

Across the animal kingdom, environmental light cues are widely involved in regulating gamete release, but the molecular and cellular bases of the photoresponsive mechanisms are poorly understood. In hydrozoan jellyfish, spawning is triggered by dark-light or light-dark transitions acting on the gonad, and is mediated by oocyte maturation-inducing neuropeptide hormones (MIHs) released from the ectoderm. We determined in Clytia hemisphaerica that blue-cyan light triggers spawning in isolated gonads. A candidate opsin (Opsin9) was found co-expressed with MIH within specialised ectodermal cells. Opsin9 knockout jellyfish generated by CRISPR/Cas9 failed to undergo oocyte maturation and spawning, a phenotype reversible by synthetic MIH. Gamete maturation and release in Clytia is thus regulated by gonadal photosensory-neurosecretory cells that secrete MIH in response to light via Opsin9. Similar cells in ancestral eumetazoans may have allowed tissue-level photo-regulation of diverse behaviours, a feature elaborated in cnidarians in parallel with expansion of the opsin gene family. PMID:29303477

Establishment of Functional Genomics Pipeline in Mouse Epiblast-Like Tissue by Combining Transcriptomic Analysis and Gene Knockdown/Knockin/Knockout, Using RNA Interference and CRISPR/Cas9.

PubMed

Takata, Nozomu; Sakakura, Eriko; Kasukawa, Takeya; Sakuma, Tetsushi; Yamamoto, Takashi; Sasai, Yoshiki

2016-06-01

The epiblast (foremost embryonic ectoderm) generates all three germ layers and therefore has crucial roles in the formation of all mammalian body cells. However, regulation of epiblast gene expression is poorly understood because of the difficulty of manipulating epiblast tissues in vivo. In the present study, using the self-organizing properties of mouse embryonic stem cell (ESC), we generated and characterized epiblast-like tissue in three-dimensional culture. We identified significant genome-wide gene expression changes in this epiblast-like tissue by transcriptomic analysis. In addition, we identified the particular significance of the Erk/Mapk and integrin-linked kinase pathways, and genes related to ectoderm/epithelial formation, using the bioinformatics resources IPA and DAVID. Here, we focused on Fgf5, which ranked in the top 10 among the discovered genes. To develop a functional analysis of Fgf5, we created an efficient method combining CRISPR/Cas9-mediated genome engineering and RNA interference (RNAi). Notably, we show one-step generation of various Fgf5 reporter lines including heterozygous and homozygous knockins (the GET method). For time- and dose-dependent depletion of fgf5 over the course of development, we generated an ESC line harboring Tol2 transposon-mediated integration of an inducible short hairpin RNA interference system (pdiRNAi). Our findings raised the possibility that Fgf/Erk signaling and apicobasal epithelial integrity are important factors in epiblast development. In addition, our methods provide a framework for a broad array of applications in the areas of mammalian genetics and molecular biology to understand development and to improve future therapeutics.

Removable partial dentures vs overdentures in children with ectodermal dysplasia: two case reports.

PubMed

Maroulakos, G; Artopoulou, I I; Angelopoulou, M V; Emmanouil, D

2016-06-01

Ectodermal dysplasia (ED) represents a disorder group characterised by abnormal development of the ectodermal derivatives. Removable partial dentures (RPD), complete dentures (CD) or overdentures (OD) are most often the treatment of choice for young affected patients. Prosthetic intervention is of utmost importance in the management of ED patients, as it resolves problems associated with functional, aesthetic, and psychological issues, and improves a patient's quality of life. However, few studies present the principles and guidelines that can assist in the decision-making process of the most appropriate removable prosthesis. The purpose of this study was to suggest a simple treatment decision-making algorithm for selecting an effective and individualised rehabilitative treatment plan, considering different parameters. The cases and treatment of two young ED patients are described and each one was treated with either RPDs or ODs. Periodic recalls were employed to manage problems, and monitor the changes associated with occlusion and fit of the prostheses in relation to each patient's growth. Both patients were followed up for more than 2 years and reported significant improvement in their appearance, masticatory function, and social behaviour as a result of the prosthetic rehabilitation. The main factors guiding the decision process towards the choice of an RPD or an OD are the presence of posterior natural teeth, facial aesthetics, lip support, number and size of existing natural teeth, and the occlusal vertical dimension.

Signaling by Bone Morphogenetic Proteins directs formation of an ectodermal signaling center that regulates craniofacial development

PubMed Central

Foppiano, Silvia; Hu, Diane; Marcucio, Ralph S.

2008-01-01

We previously described a signaling center, the Frontonasal Ectodermal Zone (FEZ) that regulates growth and patterning of the frontonasal process (FNP). The FEZ is comprised of FNP ectoderm flanking a boundary between Sonic hedgehog (Shh) and Fibroblast growth factor 8 (Fgf8) expression domains. Our objective was to examine BMP signaling during formation of the FEZ. We blocked BMP signaling throughout the FNP prior to FEZ formation by infecting chick embryos at stage 10 (HH10) with a replication competent avian retrovirus encoding the BMP antagonist Noggin. We assessed gene expression patterns in the FNP 72 hours after infection (~HH22) and observed that Shh expression was reduced or absent. In the mesenchyme we observed that Bmp2 transcripts were absent while the Bmp4 expression domain was expanded proximally. In addition to the molecular changes, infected embryos also exhibited facial malformations at 72 and 96 hours after infection suggesting that the FEZ did not form. Our data indicate that reduced cell proliferation, but not apoptosis, in the mesenchyme contributed to the phenotype that we observed. Additionally, adding exogenous SHH into the mesenchyme of RCAS-Noggin infected embryos did not restore Bmp2 and Bmp4 to a normal pattern of expression. These data indicate that BMP signaling mediates interactions between tissues in the FNP that regulate FEZ formation; and that the correct pattern of Bmp2 and Bmp4, but not Bmp7, expression in the FNP mesenchyme requires signaling by the BMP pathway. PMID:18028903

Chicken homeobox gene Msx-1: structure, expression in limb buds and effect of retinoic acid.

PubMed

Yokouchi, Y; Ohsugi, K; Sasaki, H; Kuroiwa, A

1991-10-01

A chicken gene carrying a homeobox highly homologous to the Drosophila muscle segment homeobox (msh) gene was isolated and designated as Msx-1. Conceptual translation from the longest ORF gave a protein of 259 amino acids lacking the conserved hexapeptide. Northern analysis detected a single 2.6 kb transcript. As early as day 2 of incubation, the transcript was detected but was not found in adult tissue. In situ hybridization analysis revealed that Msx-1 expression is closely related to a particular mesenchymal cell lineage during limb bud formation. In early stage embryos, Msx-1 was expressed in the somatopleure. When primordial mesenchyme cells for limb bud were generated from the Wolffian ridge of the somatopleure, Msx-1 expression began to diminish in the posterior half of the limb bud then in the presumptive cartilage-forming mesenchyme. In developing limb buds, remarkable expression was seen in the apical ectodermal ridge (AER), which is responsible for the sustained outgrowth and development of the limb. The Msx-1 transcripts were found in the limb mesenchymal cells in the region covering the necrotic zone and ectodermal cells overlying such mesenchymal cells. Both ectodermal and mesenchymal expression in limb bud were rapidly suppressed by local treatment of retinoic acid which can generate mirror-image duplication of digits. This indicates that retinoic acid alters the marginal presumptive non-cartilage forming mesenchyme cell lineage through suppression of Msx-1 expression.

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates.

PubMed

Plouhinec, Jean-Louis; Medina-Ruiz, Sofía; Borday, Caroline; Bernard, Elsa; Vert, Jean-Philippe; Eisen, Michael B; Harland, Richard M; Monsoro-Burq, Anne H

2017-10-01

During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal component analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes directly from its transcriptome. In parallel, we use nonnegative matrix factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g., Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research.

Hypohidrotic ectodermal dysplasia: a clinical case with a longitudinal approach.

PubMed

Fraiz, Fabian Calixto; Gugisch, Renato Cordeiro; Cavalcante-Leão, Bianca Lopes; Macedo, Liliane Moreira

2014-11-01

This paper describes a clinical case of a male with hypohidrotic ectodermal dysplasia submitted to rehabilitation and occlusal dental interventions with follow-up from 3 to 14 years of age. Due to the severe effects on function and esthetics, the clinical manifestations of ectodermal dysplasia exert a negative impact on quality of life. However, oral rehabilitation in childhood poses a challenge due to growth and development. A male with hypohidrotic ectodermal dysplasia began dental intervention at the age of 3 years. The clinical and radiographic exams revealed the absence of several primary and permanent teeth and abnormal shape of the primary maxillary incisors. The facial characteristics were compatible with hypohidrotic ectodermal dysplasia, such as a prominent brow, everted lips, fattened bridge of the nose and small vertical facial height. The treatment proposed involved rehabilitation through successive temporary partial dentures, functional orthopedics of the jaws, esthetic reconstruction of the anterior teeth, timely occlusal intervention and preventive actions for the control of dental caries and plaque. The present case demonstrates that early care plays a fundamental role in minimizing the biopsychosocial consequences of hypohidrotic ectodermal dysplasia and preparing the patient for future oral rehabilitation. Although, the literature offers a number of papers describing dental treatment for ectodermal dysplasia, few cases include long-term follow-up and the use of a functional orthopedic appliance in combination with removable dentures in such patients.

A molecular atlas of the developing ectoderm defines neural, neural crest, placode, and nonneural progenitor identity in vertebrates

PubMed Central

Borday, Caroline; Bernard, Elsa; Vert, Jean-Philippe; Eisen, Michael B.; Harland, Richard M.

2017-01-01

During vertebrate neurulation, the embryonic ectoderm is patterned into lineage progenitors for neural plate, neural crest, placodes and epidermis. Here, we use Xenopus laevis embryos to analyze the spatial and temporal transcriptome of distinct ectodermal domains in the course of neurulation, during the establishment of cell lineages. In order to define the transcriptome of small groups of cells from a single germ layer and to retain spatial information, dorsal and ventral ectoderm was subdivided along the anterior-posterior and medial-lateral axes by microdissections. Principal component analysis on the transcriptomes of these ectoderm fragments primarily identifies embryonic axes and temporal dynamics. This provides a genetic code to define positional information of any ectoderm sample along the anterior-posterior and dorsal-ventral axes directly from its transcriptome. In parallel, we use nonnegative matrix factorization to predict enhanced gene expression maps onto early and mid-neurula embryos, and specific signatures for each ectoderm area. The clustering of spatial and temporal datasets allowed detection of multiple biologically relevant groups (e.g., Wnt signaling, neural crest development, sensory placode specification, ciliogenesis, germ layer specification). We provide an interactive network interface, EctoMap, for exploring synexpression relationships among genes expressed in the neurula, and suggest several strategies to use this comprehensive dataset to address questions in developmental biology as well as stem cell or cancer research. PMID:29049289

Msx homeobox gene family and craniofacial development.

PubMed

Alappat, Sylvia; Zhang, Zun Yi; Chen, Yi Ping

2003-12-01

Vertebrate Msx genes are unlinked, homeobox-containing genes that bear homology to the Drosophila muscle segment homeobox gene. These genes are expressed at multiple sites of tissue-tissue interactions during vertebrate embryonic development. Inductive interactions mediated by the Msx genes are essential for normal craniofacial, limb and ectodermal organ morphogenesis, and are also essential to survival in mice, as manifested by the phenotypic abnormalities shown in knockout mice and in humans. This review summarizes studies on the expression, regulation, and functional analysis of Msx genes that bear relevance to craniofacial development in humans and mice. Key words: Msx genes, craniofacial, tooth, cleft palate, suture, development, transcription factor, signaling molecule.

Regulation of scapula development.

PubMed

Huang, Ruijin; Christ, Bodo; Patel, Ketan

2006-12-01

The scapula is a component of the shoulder girdle. Its structure has changed greatly during evolution. For example, in humans it is a large quite flat triangular bone whereas in chicks it is a long blade like structure. In this review we describe the mechanisms that control the formation of the scapula. To assimilate our understanding regarding the development of the scapula blade we start by addressing the issue concerning the origin of the scapula. Experiments using somite extirpation, chick-quail cell marking system and genetic cell labelling techniques in a variety of species have suggested that the scapula had its origin in the somites. For example we have shown in the chick that the scapula blade originates from the somite, while the cranial part, which articulates with the upper limb, is derived from the somatopleure of the forelimb field. In the second and third part of the review we discuss the compartmental origin of this bone and the signalling molecules that control the scapula development. It is very interesting that the scapula blade originates from the dorsal compartment, dermomyotome, which has been previously been associated as a source of muscle and dermis, but not of cartilage. Thus, the development of the scapula blade can be considered a case of dermomyotomal chondrogenesis. Our results show that the dermomyotomal chondrogenesis differ from the sclerotomal chondrogenesis. Firstly, the scapula precursors are located in the hypaxial domain of the dermomyotome, from which the hypaxial muscles are derived. The fate of the scapula precursors, like the hypaxial muscle, is controlled by ectoderm-derived signals and BMPs from the lateral plate mesoderm. Ectoderm ablation and inhibition of BMP activity interfers the scapula-specific Pax1 expression and scapula blade formation. However, only somite cells in the cervicothoracic transition region appear to be committed to form scapula. This indicates that the intrinsic segment specific information determines the scapula forming competence of the somite cells. Taken together, we conclude that the scapula forming cells located within the hypaxial somitic domain require BMP signals derived from the somatopleure and as yet unidentified signals from ectoderm for activation of their coded intrinsic segment specific chondrogenic programme. In the last part we discuss the new data that provides evidence that neural crest contributes for the development of the scapula.

Mini-implants: alternative for oral rehabilitation of a child with ectodermal dysplasia.

PubMed

Mello, Bianca Zeponi Fernandes; Silva, Thiago Cruvinel; Rios, Daniela; Machado, Maria Aparecida Andrade Moreira; Valarelli, Fabrício Pinelli; Oliveira, Thais Marchini

2015-01-01

Ectodermal dysplasia is a rare congenital disease that affects several structures of ectodermal origin. The most commonly related oral characteristics are hypodontia, malformed teeth and underdeveloped alveolar ridges. New alternative treatments are needed due to the failure of the conventional prosthesis retention. This case report outlines the oral rehabilitation treatment of a 9-year-old girl with ectodermal dysplasia. The treatment was performed with conventional prosthesis upon mini-implants. The mini-implants provided prosthetic retention. The patient reported a good adaptation of the dental prosthesis and satisfaction with the treatment. The increased self-esteem improved the socialization skills of the girl. In this case report, use of prosthesis with mini-implants was satisfactory for prosthetic retention. However, clinical studies with long-term follow-up are needed to test the mini-implants as an alternative for oral rehabilitation of children with ectodermal dysplasia.

Ectodermal Dysplasia with Anodontia: A Report of Two Cases

PubMed Central

Bani, Mehmet; Tezkirecioglu, Ali Melih; Akal, Nese; Tuzuner, Tamer

2010-01-01

Ectodermal dysplasia is a hereditary disorder that occurs as a consequence of disturbances in the ectoderm of the developing embryo. The triad of nail dystrophy, alopecia or hypotrichosis and palmoplantar hyperkeratosis is usually accompanied by a lack of sweat glands and a partial or complete absence of primary and/or permanent dentition. Two case reports illustrating the prosthetic rehabilitation of 2 young boys with anhidrotic ectodermal dysplasia associated with severe anodontia are presented. Since the oral rehabilitation of these cases is often difficult; particularly in pediatric patients, treatment should be administered by a multidisciplinary team involving pediatric dentistry, orthodontics, prosthodontics and oral-maxillofacial surgery. PMID:20396456

Ectodermal Dysplasia: A Clinical Overview for the Dental Practitioner.

PubMed

Halai, Tina; Stevens, Claire

2015-10-01

The term ectodermal dysplasia (ED) is used to describe a group of rare congenital disorders characterized by abnormalities of two or more ectodermal structures such as the skin, hair, nails, teeth and sweat glands. This paper will give an overview of the aetiology of ED and describe the manifestations and dental management of this condition. In particular, the important role of the dental practitioner in the identification and management of patients with ED will be highlighted. CPD/Clinical Relevance: Dental practitioners should be aware of the oral features of ectodermal dysplasia and be able to make timely referrals and provide appropriate continuing care for these patients.

Acro-Dermato-Ungual-Lacrimal-Tooth Syndrome: An Uncommon Member of the Ectodermal Dysplasias.

PubMed

Whittington, Adam; Stein, Sarah; Kenner-Bell, Brandi

2016-09-01

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare form of autosomal dominant ectodermal dysplasia due to mutations in the TP63 gene, a locus that has also been implicated in other syndromic forms of ectodermal dysplasia. It shares many phenotypic characteristics with other TP63 gene mutation syndromes, often making an accurate diagnosis difficult. Long-term management and follow-up of the various sequelae of ectodermal dysplasia require an accurate diagnosis. We report a familial case of ADULT syndrome in a daughter, mother, and son and provide a brief review of the clinical characteristics of this syndrome. © 2016 Wiley Periodicals, Inc.

Ectodermal Dysplasia: A Genetic Review

PubMed Central

Prashanth, S

2012-01-01

Abstract Ectodermal dysplasia is a rare hereditary disorder with a characteristic physiognomy. It is a genetic disorder affecting the development or function of the teeth, hair, nails and sweat glands. Depending on the particular syndrome ectodermal dysplasia can also affect the skin, the lens or retina of the eye, parts of the inner ear, the development of fingers and toes, the nerves and other parts of the body. Each syndrome usually involves a different combination of symptoms, which can range from mild to severe. The history and lessons learned from hypohidrotic ectodermal dysplasia (HED) may serve as an example for unraveling of the cause and pathogenesis of other ectodermal dysplasia syndromes by demonstrating that phenotypically identical syndromes can be caused by mutations in different genes (EDA, EDAR, EDARADD), that mutations in the same gene can lead to different phenotypes and that mutations in the genes further downstream in the same signaling pathway (NEMO) may modify the phenotype quite profoundly. The aim of this paper is to describe and discuss the etiology, genetic review, clinical manifestations and treatment options of this hereditary disorder. How to cite this article: Deshmukh S, Prashanth S. Ectodermal Dysplasia: A Genetic Review. Int J Clin Pediatr Dent 2012; 5(3):197-202. PMID:25206167

Ectodermal dysplasia: a genetic review.

PubMed

Deshmukh, Seema; Prashanth, S

2012-09-01

Ectodermal dysplasia is a rare hereditary disorder with a characteristic physiognomy. It is a genetic disorder affecting the development or function of the teeth, hair, nails and sweat glands. Depending on the particular syndrome ectodermal dysplasia can also affect the skin, the lens or retina of the eye, parts of the inner ear, the development of fingers and toes, the nerves and other parts of the body. Each syndrome usually involves a different combination of symptoms, which can range from mild to severe. The history and lessons learned from hypohidrotic ectodermal dysplasia (HED) may serve as an example for unraveling of the cause and pathogenesis of other ectodermal dysplasia syndromes by demonstrating that phenotypically identical syndromes can be caused by mutations in different genes (EDA, EDAR, EDARADD), that mutations in the same gene can lead to different phenotypes and that mutations in the genes further downstream in the same signaling pathway (NEMO) may modify the phenotype quite profoundly. The aim of this paper is to describe and discuss the etiology, genetic review, clinical manifestations and treatment options of this hereditary disorder. How to cite this article: Deshmukh S, Prashanth S. Ectodermal Dysplasia: A Genetic Review. Int J Clin Pediatr Dent 2012; 5(3):197-202.

Regeneration of a Tooth in a Tissue-Engineered Mandible After Resection of a Central Giant Cell Tumor. Demonstrating Evidence of Functional Matrix Theory and Ectodermal Origin of Teeth in a Human Model-A Case Report.

PubMed

Melville, James C; Couey, Marcus A; Tong, Matthew S; Marx, Robert E

2017-04-01

Central giant cell tumors (CGCTs) are uncommon lesions occurring in the jaw. They are benign but locally destructive osteolytic lesions. They usually occur in pediatric patients 5 to 15 years of age. Multiple noninvasive modalities of treatment (intralesional steroids, interferon, calcitonin, and denosumab) have been described for those lesions, but for those that are refractory to treatment, enucleation and curettage or resection is a curative surgery. This case report describes a pediatric patient who was diagnosed with an aggressive CGCT of the left mandible encompassing the right angle to the condyle. The lesion became refractory to noninvasive treatments and immediate resection and reconstruction was performed using principles of tissue engineering. After 5 years of close observation, the patient showed normal morphology and growth of his mandible, but surprisingly developed a left mandibular third molar (tooth 17) in the site of the mandibular resection and reconstruction. This is the first case report in the literature to show the spontaneous development of teeth in a human reconstructed mandible, contributing evidence toward the functional matrix theory of mandibular growth and ectodermal origin of teeth. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

[Prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia with X-chromosome inversion].

PubMed

Shi, Hui-juan; Fang, Qun; Wang, Lian-tang

2005-07-13

To investigate the possibility of prenatal diagnosis of the fetal suspected to be affected by anhidrotic ectodermal dysplasia (EDA) in a family with X-linked EDA so as to provide a basis for prenatal diagnosis and genetic counseling of this disorder. Pedigree analysis and genetic counseling were performed in a family after a proband was diagnosed with EDA. The peripheral blood samples were collected from the proband, a 12-year-old boy, his mother, and his 2 aunts, one being pregnant, to undergo chromosome karyotype analysis. The fetus Puncture of umbilical vein was performed to collect the blood of fetus for chromosome examination. Induced abortion was conducted due to the diagnosis of the fetus with EDA. Autopsy, immunohistochemistry of the skin tissues of face, breast, epigastrium, and thigh, and X-ray photography of the lower jawbone were made. Pericentric inversion occurring at one of the X-chromosome [inv (x) (p22q13)] was found in the proband and his nephew (the fetus), both patients, and his mother and his second aunt (the pregnant woman), both carriers. Autopsy of the fetus showed epidermis dysplasia and deficiency of hair follicle and sebaceous gland. Immunohistochemistry showed that epithelial membrane antigen and cytokeratin were negatively expressed in the fetal skin tissues. Pedigree analysis and genetic counseling for the family members of EDA patients and prenatal and postpartum examination for the fetus help diagnose EDA.

In vivo imaging of coral tissue and skeleton with optical coherence tomography.

PubMed

Wangpraseurt, Daniel; Wentzel, Camilla; Jacques, Steven L; Wagner, Michael; Kühl, Michael

2017-03-01

Application of optical coherence tomography (OCT) for in vivo imaging of tissue and skeleton structure of intact living corals enabled the non-invasive visualization of coral tissue layers (endoderm versus ectoderm), skeletal cavities and special structures such as mesenterial filaments and mucus release from intact living corals. Coral host chromatophores containing green fluorescent protein-like pigment granules appeared hyper-reflective to near-infrared radiation allowing for excellent optical contrast in OCT and a rapid characterization of chromatophore size, distribution and abundance. In vivo tissue plasticity could be quantified by the linear contraction velocity of coral tissues upon illumination resulting in dynamic changes in the live coral tissue surface area, which varied by a factor of 2 between the contracted and expanded state of a coral. Our study provides a novel view on the in vivo organization of coral tissue and skeleton and highlights the importance of microstructural dynamics for coral ecophysiology. © 2017 The Author(s).

Identification and embryonic expression of a new AP-2 transcription factor, AP-2 epsilon.

PubMed

Wang, Hao-Ven; Vaupel, Kristina; Buettner, Reinhard; Bosserhoff, Anja-Katrin; Moser, Markus

2004-09-01

AP-2 proteins comprise a family of highly related transcription factors, which are expressed during mouse embryogenesis in a variety of ectodermal, neuroectodermal, and mesenchymal tissues. AP-2 transcription factors were shown to be involved in morphogenesis of craniofacial, urogenital, neural crest-derived, and placental tissues. By means of a partial cDNA fragment identified during an expressed sequence tag search for AP-2 genes, we identified a fifth, previously unknown AP-2-related gene, AP-2 epsilon. AP-2 epsilon encodes an open reading frame of 434 amino acids, which reveals the typical modular structure of AP-2 transcription factors with highly conserved C-terminal DNA binding and dimerization domains. Although the N-terminally localized activation domain is less homologous, position and identity of amino acids essential for transcriptional transactivation are conserved. Reverse transcriptase-polymerase chain reaction analyses of murine embryos revealed AP-2 epsilon expression from gestational stage embryonic day 7.5 throughout all later embryonic stages until birth. Whole-mount in situ hybridization using a specific AP-2 epsilon cDNA fragment demonstrated that during embryogenesis, expression of AP-2 epsilon is mainly restricted to neural tissue, especially the midbrain, hindbrain, and olfactory bulb. This expression pattern was confirmed by immunohistochemistry with an AP-2 epsilon-specific antiserum. By using this antiserum, we could further localize AP-2 epsilon expression in a hypothalamic nucleus and the neuroepithelium of the vomeronasal organ, suggesting an important function of AP-2 epsilon for the development of the olfactory system.

Evaluation of the Adult Goldfish Brain as a Model for the Study of Progenitor Cells

DTIC Science & Technology

2007-08-27

embryo [34]. ESCs are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm, and they are...postnatal brain is their functional and anatomical destiny . Based on many reports investigating neurogenesis, the majority of newly produced cells...Homeodomain-bearing transcriptional factor. Expression is specific to early embryos and pluripotential stem cells. Key molecule involved in the

Trends in the human embryonic stem cell patent field.

PubMed

Karlsson, Ulrika; Hyllner, Johan; Runeberg, Kristina

2007-01-01

The successful derivation of human embryonic stem (hES) cell lines in late 1990s marks the birth of a new era in biomedical research. In the USA, this landmark invention is protected by granted composition-of-matter patents. In addition to these patents, several others have been granted on further development of hES cell research, such as on differentiated cell types and in vitro and in vivo use aspects. In Europe, there is presently no consensus pertaining to the patentability of hES cells, and all patent applications pending at the European patent office are therefore awaiting a principal decision by the Enlarged Board of Appeal. The authors argue that it will be of importance to the stem cell industry that patents are granted on inventions downstream in the value chain, e.g on specialised cell types derived from hES cells and different drug discovery applications. Patents and patent applications on such inventions for the three germ layers ectoderm/neuro, endoderm/hepato and mesoderm/cardio have been examined. The number of patents increased in the period 2001 to 2006 for all three lineages with ectoderm/neuro as the most patent intensive field. There where 9-13 times more US patent applications filed related to the three lineages compared to in Europe.

A new scenario for the evolutionary origin of hair, feather, and avian scales

PubMed Central

Dhouailly, Danielle

2009-01-01

In zoology it is well known that birds are characterized by the presence of feathers, and mammals by hairs. Another common point of view is that avian scales are directly related to reptilian scales. As a skin embryologist, I have been fascinated by the problem of regionalization of skin appendages in amniotes throughout my scientific life. Here I have collected the arguments that result from classical experimental embryology, from the modern molecular biology era, and from the recent discovery of new fossils. These arguments shape my view that avian ectoderm is primarily programmed toward forming feathers, and mammalian ectoderm toward forming hairs. The other ectoderm derivatives – scales in birds, glands in mammals, or cornea in both classes – can become feathers or hairs through metaplastic process, and appear to have a negative regulatory mechanism over this basic program. How this program is altered remains, in most part, to be determined. However, it is clear that the regulation of the Wnt/beta-catenin pathway is a critical hub. The level of beta-catenin is crucial for feather and hair formation, as its down-regulation appears to be linked with the formation of avian scales in chick, and cutaneous glands in mice. Furthermore, its inhibition leads to the formation of nude skin and is required for that of corneal epithelium. Here I propose a new theory, to be further considered and tested when we have new information from genomic studies. With this theory, I suggest that the alpha-keratinized hairs from living synapsids may have evolved from the hypothetical glandular integument of the first amniotes, which may have presented similarities with common day terrestrial amphibians. Concerning feathers, they may have evolved independently of squamate scales, each originating from the hypothetical roughened beta-keratinized integument of the first sauropsids. The avian overlapping scales, which cover the feet in some bird species, may have developed later in evolution, being secondarily derived from feathers. PMID:19422430

FOXI2: a possible gene contributing to ectodermal dysplasia.

PubMed

Kurban, Mazen; Zeineddine, Savo Bou; Hamie, Lamiaa; Safi, Remi; Abbas, Ossama; Kibbi, Abdul Ghani; Bitar, Fadi; Nemer, Georges

2017-12-01

Cardio-facio-cutaneous syndrome (CFC), Noonan syndrome (NS), and Costello syndrome are a group of diseases that belong to the RASopathies. The syndromes share clinical features making diagnosis a challenge. To investigate the phenotype and genotype of a 10-year-old Iraqi girl with overlapping features of CFC, NS, and Costello syndromes, with additional features of ectodermal dysplasia. DNA was examined by exome sequencing and protein expression by immunohistochemistry. Exome sequencing identified a mutation in the SOS1 gene and a de novo deletion in the FOXI2 gene which was neither present in the international databases, nor in 400 chromosomes from the same population. Based on immunohistochemical staining, FOXI2 was identified in the basal cell layer of the skin and overlapped with the expression of P63, a major player in ectodermal dysplasia. We therefore suggest screening for FOXI2 mutation in the setting of ectodermal features that are not associated with genes known to contribute to ectodermal dysplasia.

Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

PubMed

Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J; Schneider, Pascal

2014-02-14

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated.

Generation and Characterization of Function-blocking Anti-ectodysplasin A (EDA) Monoclonal Antibodies That Induce Ectodermal Dysplasia*

PubMed Central

Kowalczyk-Quintas, Christine; Willen, Laure; Dang, Anh Thu; Sarrasin, Heidi; Tardivel, Aubry; Hermes, Katharina; Schneider, Holm; Gaide, Olivier; Donzé, Olivier; Kirby, Neil; Headon, Denis J.; Schneider, Pascal

2014-01-01

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA. These antibodies recognize epitopes overlapping the receptor-binding site and prevent EDA from binding and activating EDAR at close to stoichiometric ratios in in vitro binding and activity assays. The antibodies block EDA1 and EDA2 of both mammalian and avian origin and, in vivo, suppress the ability of recombinant Fc-EDA1 to rescue ectodermal dysplasia in Eda-deficient Tabby mice. Moreover, administration of EDA blocking antibodies to pregnant wild type mice induced in developing wild type fetuses a marked and permanent ectodermal dysplasia. These function-blocking anti-EDA antibodies with wide cross-species reactivity will enable study of the developmental and postdevelopmental roles of EDA in a variety of organisms and open the route to therapeutic intervention in conditions in which EDA may be implicated. PMID:24391090

Molecular genetic analysis of consanguineous Pakistani families with autosomal recessive hypohidrotic ectodermal dysplasia.

PubMed

Bibi, Nosheen; Ahmad, Saeed; Ahmad, Wasim; Naeem, Muhammad

2011-02-01

Hypohidrotic ectodermal dysplasia is an inherited disorder characterized by defective development of teeth, hairs and sweat glands. X-linked hypohidrotic ectodermal dysplasia is caused by mutations in the EDA gene, and autosomal forms of hypohidrotic ectodermal dysplasia are caused by mutations in either the EDAR or the EDARADD genes. To study the molecular genetic cause of autosomal recessive hypohidrotic ectodermal dysplasia in three consanguineous Pakistani families (A, B and C), genotyping of 13 individuals was carried out by using polymorphic microsatellite markers that are closely linked to the EDAR gene on chromosome 2q11-q13 and the EDARADD gene on chromosome 1q42.2-q43. The results revealed linkage in the three families to the EDAR locus. Sequence analysis of the coding exons and splice junctions of the EDAR gene revealed two mutations: a novel non-sense mutation (p.E124X) in the probands of families A and B and a missense mutation (p.G382S) in the proband of family C. In addition, two synonymous single-nucleotide polymorphisms were also identified. The finding of mutations in Pakistani families extends the body of evidence that supports the importance of EDAR for the development of hypohidrotic ectodermal dysplasia. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

Ectodermal Wnt signaling regulates abdominal myogenesis during ventral body wall development.

PubMed

Zhang, Lingling; Li, Hanjun; Yu, Jian; Cao, Jingjing; Chen, Huihui; Zhao, Haixia; Zhao, Jianzhi; Yao, Yiyun; Cheng, Huihui; Wang, Lifang; Zhou, Rujiang; Yao, Zhengju; Guo, Xizhi

2014-03-01

Defects of the ventral body wall are prevalent birth anomalies marked by deficiencies in body wall closure, hypoplasia of the abdominal musculature and multiple malformations across a gamut of organs. However, the mechanisms underlying ventral body wall defects remain elusive. Here, we investigated the role of Wnt signaling in ventral body wall development by inactivating Wls or β-catenin in murine abdominal ectoderm. The loss of Wls in the ventral epithelium, which blocks the secretion of Wnt proteins, resulted in dysgenesis of ventral musculature and genito-urinary tract during embryonic development. Molecular analyses revealed that the dermis and myogenic differentiation in the underlying mesenchymal progenitor cells was perturbed by the loss of ectodermal Wls. The activity of the Wnt-Pitx2 axis was impaired in the ventral mesenchyme of the mutant body wall, which partially accounted for the defects in ventral musculature formation. In contrast, epithelial depletion of β-catenin or Wnt5a did not resemble the body wall defects in the ectodermal Wls mutant. These findings indicate that ectodermal Wnt signaling instructs the underlying mesodermal specification and abdominal musculature formation during ventral body wall development, adding evidence to the theory that ectoderm-mesenchyme signaling is a potential unifying mechanism for the origin of ventral body wall defects. Copyright © 2013 Elsevier Inc. All rights reserved.

Dental and maxillofacial characteristics of six Japanese individuals with ectrodactyly-ectodermal dysplasia-clefting syndrome.

PubMed

Okamura, Erika; Suda, Naoto; Baba, Yoshiyuki; Fukuoka, Hiroki; Ogawa, Takuya; Ohkuma, Mizue; Ahiko, Nozomi; Yasue, Akihiro; Tengan, Toshimoto; Shiga, Momotoshi; Tsuji, Michiko; Moriyama, Keiji

2013-03-01

Objective : Ectrodactyly-ectodermal dysplasia-clefting syndrome is a congenital anomaly characterized by ectodermal dysplasia, ectrodactyly, cleft lip and palate, and lacrimal duct anomalies. Because this syndrome is frequently accompanied by a congenital lack of teeth, narrow palate, and malocclusion, comprehensive orthodontic intervention is required. Design : To highlight the specific dental and maxillofacial characteristics of ectrodactyly-ectodermal dysplasia-clefting syndrome, six Japanese individuals diagnosed with the syndrome are described here. Patients : The subjects consisted of two boys and four girls (age range, 6.0 to 13.9 years) diagnosed with ectrodactyly-ectodermal dysplasia-clefting syndrome by medical and dental specialists. Their conditions included ectodermal dysplasia (hypodontia, microdontia, enamel hypoplasia, and abnormalities in hair and nails), cleft lip and/or palate, and ectrodactyly. Cephalograms, panoramic x-rays, and dental casts were taken; systemic complications were recorded at the first visit to our dental hospital. Results : All individuals had severe oligodontia with 9 to 18 missing teeth. The missing teeth were mainly maxillary and mandibular incisors and second bicuspids, arranged in a symmetrical manner. Cephalometric analysis showed retruded and short maxilla due to cleft lip and/or palate. It is interesting that all individuals showed a characteristically shaped mandibular symphysis with a retruded point B. It is likely that this unusual symphyseal morphology is due to the lack of mandibular incisors. Conclusions : This study demonstrates the presence of severe oligodontia in the incisal and premolar regions and describes a characteristic maxillary and mandibular structure in Japanese individuals with ectrodactyly-ectodermal dysplasia-clefting syndrome.

cis-Regulatory control of the initial neurogenic pattern of onecut gene expression in the sea urchin embryo.

PubMed

Barsi, Julius C; Davidson, Eric H

2016-01-01

Specification of the ciliated band (CB) of echinoid embryos executes three spatial functions essential for postgastrular organization. These are establishment of a band about 5 cells wide which delimits and bounds other embryonic territories; definition of a neurogenic domain within this band; and generation within it of arrays of ciliary cells that bear the special long cilia from which the structure derives its name. In Strongylocentrotus purpuratus the spatial coordinates of the future ciliated band are initially and exactly determined by the disposition of a ring of cells that transcriptionally activate the onecut homeodomain regulatory gene, beginning in blastula stage, long before the appearance of the CB per se. Thus the cis-regulatory apparatus that governs onecut expression in the blastula directly reveals the genomic sequence code by which these aspects of the spatial organization of the embryo are initially determined. We screened the entire onecut locus and its flanking region for transcriptionally active cis-regulatory elements, and by means of BAC recombineered deletions identified three separated and required cis-regulatory modules that execute different functions. The operating logic of the crucial spatial control module accounting for the spectacularly precise and beautiful early onecut expression domain depends on spatial repression. Previously predicted oral ectoderm and aboral ectoderm repressors were identified by cis-regulatory mutation as the products of goosecoid and irxa genes respectively, while the pan-ectodermal activator SoxB1 supplies a transcriptional driver function. Copyright © 2015. Published by Elsevier Inc.

Exogenous retinoic acid induces digit reduction in opossums (Monodelphis domestica) by disrupting cell death and proliferation, and apical ectodermal ridge and zone of polarizing activity function.

PubMed

Molineaux, Anna C; Maier, Jennifer A; Schecker, Teresa; Sears, Karen E

2015-03-01

Retinoic acid (RA) is a vitamin A derivative. Exposure to exogenous RA generates congenital limb malformations (CLMs) in species from frogs to humans. These CLMs include but are not limited to oligodactyly and long-bone hypoplasia. The processes by which exogenous RA induces CLMs in mammals have been best studied in mouse, but as of yet remain unresolved. We investigated the impact of exogenous RA on the cellular and molecular development of the limbs of a nonrodent model mammal, the opossum Monodelphis domestica. Opossums exposed to exogenous retinoic acid display CLMs including oligodactly, and results are consistent with opossum development being more susceptible to RA-induced disruptions than mouse development. Exposure of developing opossums to exogenous RA leads to an increase in cell death in the limb mesenchyme that is most pronounced in the zone of polarizing activity, and a reduction in cell proliferation throughout the limb mesenchyme. Exogenous RA also disrupts the expression of Shh in the zone of polarizing activity, and Fgf8 in the apical ectodermal ridge, and other genes with roles in the regulation of limb development and cell death. Results are consistent with RA inducing CLMs in opossum limbs by disrupting the functions of the apical ectodermal ridge and zone of polarizing activity, and driving an increase in cell death and reduction of cell proliferation in the mesenchyme of the developing limb. © 2015 Wiley Periodicals, Inc.

Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk interface coordinate the transport and assembly of hypopharyngeal structures.

PubMed

Lours-Calet, Corinne; Alvares, Lucia E; El-Hanfy, Amira S; Gandesha, Saniel; Walters, Esther H; Sobreira, Débora Rodrigues; Wotton, Karl R; Jorge, Erika C; Lawson, Jennifer A; Kelsey Lewis, A; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

2014-06-15

The vertebrate head-trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head-trunk interface. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Evolutionarily conserved morphogenetic movements at the vertebrate head–trunk interface coordinate the transport and assembly of hypopharyngeal structures

PubMed Central

Lours-Calet, Corinne; Alvares, Lucia E.; El-Hanfy, Amira S.; Gandesha, Saniel; Walters, Esther H.; Sobreira, Débora Rodrigues; Wotton, Karl R.; Jorge, Erika C.; Lawson, Jennifer A.; Kelsey Lewis, A.; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

2014-01-01

The vertebrate head–trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head–trunk interface. PMID:24662046

Integrin-α5 Coordinates Assembly of Posterior Cranial Placodes in Zebrafish and Enhances Fgf-Dependent Regulation of Otic/Epibranchial Cells

PubMed Central

Bhat, Neha; Riley, Bruce B.

2011-01-01

Vertebrate sensory organs develop in part from cranial placodes, a series of ectodermal thickenings that coalesce from a common domain of preplacodal ectoderm. Mechanisms coordinating morphogenesis and differentiation of discrete placodes are still poorly understood. We have investigated whether placodal assembly in zebrafish requires Integrin- α5 (itga5), an extracellular matrix receptor initially expressed throughout the preplacodal ectoderm. Morpholino knockdown of itga5 had no detectable effect on anterior placodes (pituitary, nasal and lens), but posterior placodes developed abnormally, resulting in disorganization of trigeminal and epibranchial ganglia and reduction of the otic vesicle. Cell motion analysis in GFP-transgenic embryos showed that cell migration in itga5 morphants was highly erratic and unfocused, impairing convergence and blocking successive recruitment of new cells into these placodes. Further studies revealed genetic interactions between itga5 and Fgf signaling. First, itga5 morphants showed changes in gene expression mimicking modest reduction in Fgf signaling. Second, itga5 morphants showed elevated apoptosis in the otic/epibranchial domain, which was rescued by misexpression of Fgf8. Third, knockdown of the Fgf effector erm had no effect by itself but strongly enhanced defects in itga5 morphants. Finally, proper regulation of itga5 requires dlx3b/4b and pax8, which are themselves regulated by Fgf. These findings support a model in which itga5 coordinates cell migration into posterior placodes and augments Fgf signaling required for patterning of these tissues and cell survival in otic/epibranchial placodes. PMID:22164214

Conference Report: International Research Symposium on Ankyloblepharon-Ectodermal Defects-Cleft Lip and/or Palate (AEC) Syndrome

PubMed Central

Fete, Mary; vanBokhoven, Hans; Clements, Suzanne; McKeon, Frank; Roop, Dennis R.; Koster, Maranke I.; Missero, Caterina; Attardi, Laura D.; Lombillo, Vivian A.; Ratovitski, Edward; Julapalli, Meena; Ruths, Derek; Sybert, Virginia P.; Siegfried, Elaine C.; Bree, Alanna F.

2009-01-01

Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate (AEC) Syndrome (Hay-Wells syndrome, MIM #106220) is a rare autosomal dominant ectodermal dysplasia syndrome. It is due to mutations in the p63 gene, known to be a regulatory gene with many downstream gene targets. TP63 is important in the differentiation and proliferation of the epidermis, as well as many other processes including limb and facial development. It is also known that mutations in p63 lead to skin erosions. These erosions, especially on the scalp, are defining features of AEC syndrome and cause significant morbidity and mortality in these patients. It was this fact that led to the 2003 AEC Skin Erosion Workshop. That conference laid the groundwork for the International Research Symposium for AEC Syndrome held at Texas Children's Hospital in 2006. The conference brought together the largest cohort of individuals with AEC syndrome, along with a multitude of physicians and scientists. The overarching goals were to define the clinical and pathologic findings for improved diagnostic criteria, to obtain tissue samples for further study and to define future research directions. The symposium was successful in accomplishing these aims as detailed in this conference report. Following our report, we also present eleven manuscripts within this special section that outline the collective clinical, pathologic and mutational data from eighteen individuals enrolled in the concurrent Baylor College of Medicine IRB-approved protocol: Characterization of AEC syndrome. These collaborative findings will hopefully provide a stepping stone to future translational projects of p63 and p63-related syndromes. PMID:19353643

Incontinentia pigmenti*

PubMed Central

Poziomczyk, Cláudia Schermann; Recuero, Júlia Kanaan; Bringhenti, Luana; Santa Maria, Fernanda Diffini; Campos, Carolina Wiltgen; Travi, Giovanni Marcos; Freitas, André Moraes; Maahs, Marcia Angelica Peter; Zen, Paulo Ricardo Gazzola; Fiegenbaum, Marilu; de Almeida, Sheila Tamanini; Bonamigo, Renan Rangel; Bau, Ana Elisa Kiszewski

2014-01-01

Incontinentia pigmenti is a rare genodermatosis in which the skin involvement occurs in all patients. Additionally, other ectodermal tissues may be affected, such as the central nervous system, eyes, hair, nails and teeth. The disease has a X-linked dominant inheritance pattern and is usually lethal to male fetuses. The dermatological findings occur in four successive phases, following the lines of Blaschko: First phase - vesicles on an erythematous base; second phase - verrucous hyperkeratotic lesions; third phase - hyperchromic spots and fourth phase - hypochromic atrophic lesions. PMID:24626645

Ewing's Sarcoma of the Adrenal Gland.

PubMed

Pal, Dilip Kumar; Chandra, Vipin; Ranjan, Kumar Rajiv; Chakrabortty, Debasis; Banerjee, Manju

2016-01-01

Ewing's sarcoma (ES) or primitive neuro-ectodermal tumor (PNET) typically occurs in long or flat bones, the chest wall, extra-skeletal soft tissue, and rarely in solid organs. Incidence of adrenal Ewing's sarcoma is very rare. Here we report a case of Ewing's sarcoma of the right adrenal gland in an 8-year-old girl who presented with an abdominal mass. The huge tumor was managed by preoperative neo-adjuvant chemotherapy followed by surgical resection. She died due to metastasis after five months of surgery.

Maternal xNorrin, a Canonical Wnt Signaling Agonist and TGF-β Antagonist, Controls Early Neuroectoderm Specification in Xenopus

PubMed Central

Xu, Suhong; Cheng, Feng; Liang, Juan; Wu, Wei; Zhang, Jian

2012-01-01

Dorsal–ventral specification in the amphibian embryo is controlled by β-catenin, whose activation in all dorsal cells is dependent on maternal Wnt11. However, it remains unknown whether other maternally secreted factors contribute to β-catenin activation in the dorsal ectoderm. Here, we show that maternal Xenopus Norrin (xNorrin) promotes anterior neural tissue formation in ventralized embryos. Conversely, when xNorrin function is inhibited, early canonical Wnt signaling in the dorsal ectoderm and the early expression of the zygotic neural inducers Chordin, Noggin, and Xnr3 are severely suppressed, causing the loss of anterior structures. In addition, xNorrin potently inhibits BMP- and Nodal/Activin-related functions through direct binding to the ligands. Moreover, a subset of Norrin mutants identified in humans with Norrie disease retain Wnt activation but show defective inhibition of Nodal/Activin-related signaling in mesoderm induction, suggesting that this disinhibition causes Norrie disease. Thus, xNorrin is an unusual molecule that acts on two major signaling pathways, Wnt and TGF-β, in opposite ways and is essential for early neuroectoderm specification. PMID:22448144

Pax8 and Pax2a function synergistically in otic specification, downstream of the Foxi1 and Dlx3b transcription factors.

PubMed

Hans, Stefan; Liu, Dong; Westerfield, Monte

2004-10-01

The vertebrate inner ear arises from an ectodermal thickening, the otic placode, that forms adjacent to the presumptive hindbrain. Previous studies have suggested that competent ectodermal cells respond to Fgf signals from adjacent tissues and express two highly related paired box transcription factors Pax2a and Pax8 in the developing placode. We show that compromising the functions of both Pax2a and Pax8 together blocks zebrafish ear development, leaving only a few residual otic cells. This suggests that Pax2a and Pax8 are the main effectors downstream of Fgf signals. Our results further provide evidence that pax8 expression and pax2a expression are regulated by two independent factors, Foxi1 and Dlx3b, respectively. Combined loss of both factors eliminates all indications of otic specification. We suggest that the Foxi1-Pax8 pathway provides an early 'jumpstart' of otic specification that is maintained by the Dlx3b-Pax2a pathway.

WNT10A missense mutation associated with a complete Odonto-Onycho-Dermal Dysplasia syndrome

PubMed Central

Nawaz, Sadia; Klar, Joakim; Wajid, Muhammad; Aslam, Muhammad; Tariq, Muhammad; Schuster, Jens; Baig, Shahid Mahmood; Dahl, Niklas

2009-01-01

Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C>T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved α-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features. PMID:19471313

WNT10A missense mutation associated with a complete odonto-onycho-dermal dysplasia syndrome.

PubMed

Nawaz, Sadia; Klar, Joakim; Wajid, Muhammad; Aslam, Muhammad; Tariq, Muhammad; Schuster, Jens; Baig, Shahid Mahmood; Dahl, Niklas

2009-12-01

Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C>T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved alpha-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features.

RNA-Sequencing Analyses Demonstrate the Involvement of Canonical Transient Receptor Potential Channels in Rat Tooth Germ Development

PubMed Central

Yang, Jun; Cai, Wenping; Lu, Xi; Liu, Shangfeng; Zhao, Shouliang

2017-01-01

Tooth development depends on multiple molecular interactions between the dental epithelium and mesenchyme, which are derived from ectodermal and ectomesenchymal cells, respectively. We report on a systematic RNA sequencing analysis of transcriptional expression levels from the bud to hard tissue formation stages of rat tooth germ development. We found that GNAO1, ENO1, EFNB1, CALM1, SIAH2, ATP6V0A1, KDELR2, GTPBP1, POLR2C, SORT1, and members of the canonical transient receptor potential (TRPC) channel family are involved in tooth germ development. Furthermore, Cell Counting Kit 8 (CCK8) and Transwell migration assays were performed to explore the effects of these differentially expressed genes (DEGs) on the proliferation and migration of dental pulp stem cells. Immunostaining revealed that TRPC channels are expressed at varying levels during odontogenesis. The identified genes represent novel candidates that are likely to be vital for rat tooth germ development. Together, the results provide a valuable resource to elucidate the gene regulatory mechanisms underlying mammalian tooth germ development. PMID:28706494

Direct and indirect requirements of Shh/Gli signaling in early pituitary development.

PubMed

Wang, Yiwei; Martin, James F; Bai, C Brian

2010-12-15

Induction of early pituitary progenitors is achieved through combined activities of signals from adjacent embryonic tissues. Previous studies have identified a requirement for oral ectoderm derived Sonic Hedgehog (Shh) in specification and/or proliferation of early pituitary progenitors, however how different Gli genes mediate Shh signaling to control pituitary progenitor development has not yet been determined. Here we show that Gli2, which encodes a major Gli activator, is required for proliferation of specific groups of pituitary progenitors but not for initial dorsoventral patterning. We further show that the action of Gli2 occurs prior to the closure of Rathke' pouch. Lastly, we show that Shh/Gli2 signaling controls the diencephalic expression of Bone morphogenetic protein 4 (Bmp4) and Fibroblast growth factor 8 (Fgf8), two genes that are known to play critical roles in patterning and growth of Rathke's pouch. Our results therefore suggest both cell-autonomous and non-cell-autonomous requirements for Gli2 in regulation of pituitary progenitor specification, proliferation and differentiation. Copyright © 2010 Elsevier Inc. All rights reserved.

Requirement of Xmsx-1 in the BMP-triggered ventralization of Xenopus embryos.

PubMed

Yamamoto, T S; Takagi, C; Ueno, N

2000-03-01

Signaling triggered by polypeptide growth factors leads to the activation of their target genes. Several homeobox genes are known to be induced in response to polypeptide growth factors in early Xenopus development. In particular, Xmsx-1, an amphibian homologue of vertebrate Msx-1, is well characterized as a target gene of bone morphogenetic protein (BMP). Here, using a dominant-negative form of Xmsx-1 (VP-Xmsx-1), which is a fusion protein made with the virus-derived VP16 activation domain, we have examined whether Xmsx-1 activity is required in the endogenous ventralizing pathway. VP-Xmsx-1 induced a secondary body axis, complete with muscle and neural tissues, when overexpressed in ventral blastomeres, suggesting that Xmsx-1 activity is necessary for both mesoderm and ectoderm to be ventralized. We have also examined the epistatic relationship between Xmsx-1 and another ventralizing homeobox protein, Xvent-1, and show that Xmsx-1 is likely to be acting upstream of Xvent-1. We propose that Xmsx-1 is required in the BMP-stimulated ventralization pathway that involves the downstream activation of Xvent-1.

Transplanted Dental Pulp Stem Cells Migrate to Injured Area and Express Neural Markers in a Rat Model of Cerebral Ischemia.

PubMed

Zhang, Xuemei; Zhou, Yinglian; Li, Hulun; Wang, Rui; Yang, Dan; Li, Bing; Cao, Xiaofang; Fu, Jin

2018-01-01

Ischemic stroke is a major cause of disability and mortality worldwide, while effective restorative treatments are limited at present. Stem cell transplantation holds therapeutic potential for ischemic vascular diseases and may provide an opportunity for neural regeneration. Dental pulp stem cells (DPSCs) origin from neural crest and have neuro-ectodermal features including proliferation and multilineage differentiation potentials. The rat model of middle cerebral artery occlusion (MCAO) was used to evaluate whether intravenous administration of DPSCs can reduce infarct size and to estimate the migration and trans-differentiation into neuron-like cells in focal cerebral ischemia models. Brain tissues were collected at 4 weeks following cell transplantation and analyzed with immunofluorescence, immunohistochemistry and real-time polymerase chain reaction (RT-PCR) methods. Intravenously administration of rat-derived DPSCs were found to migrate into the boundary of ischemic areas and expressed neural specific markers, reducing infarct volume and cerebral edema. These results suggest that DPSCs treatment may serve as a potential therapy for clinical stroke patients in the future. © 2018 The Author(s). Published by S. Karger AG, Basel.

Expression of an Msx homeobox gene in ascidians: insights into the archetypal chordate expression pattern.

PubMed

Ma, L; Swalla, B J; Zhou, J; Dobias, S L; Bell, J R; Chen, J; Maxson, R E; Jeffery, W R

1996-03-01

The Msx homeobox genes are expressed in complex patterns during vertebrate development in conjunction with inductive tissue interactions. As a means of understanding the archetypal role of Msx genes in chordates, we have isolated and characterized an Msx gene in ascidians, protochordates with a relatively simple body plan. The Mocu Msx-a and McMsx-a genes, isolated from the ascidians Molgula oculata and Molgula citrina, respectively, have homeodomains that place them in the msh-like subclass of Msx genes. Therefore, the Molgula Msx-a genes are most closely related to the msh genes previously identified in a number of invertebrates. Southern blot analysis suggests that there are one or two copies of the Msx-a gene in the Molgula genome. Northern blot and RNase protection analysis indicate that Msx-a transcripts are restricted to the developmental stages of the life cycle. In situ hybridization showed that Msx-a mRNA first appears just before gastrulation in the mesoderm (presumptive notochord and muscle) and ectoderm (neural plate) cells. Transcript levels decline in mesoderm cells after the completion of gastrulation, but are enhanced in the folding neural plate during neurulation. Later, Msx-a mRNA is also expressed in the posterior ectoderm and in a subset of the tail muscle cells. The ectoderm and mesoderm cells that express Msx-a are undergoing morphogenetic movements during gastrulation, neurulation, and tail formation. Msx-a expression ceases after these cells stop migrating. The ascidian M. citrina, in which adult tissues and organs begin to develop precociously in the larva, was used to study Msx-a expression during adult development. Msx-a transcripts are expressed in the heart primordium and the rudiments of the ampullae, epidermal protrusions with diverse functions in the juvenile. The heart and ampullae develop in regions where mesenchyme cells interact with endodermal or epidermal epithelia. A comparison of the expression patterns of the Molgula genes with those of their vertebrate congeners suggests that the archetypal roles of the Msx genes may be in morphogenetic movements during embryogenesis and in mesenchymal-epithelial interactions during organogenesis.

Evidence of accelerated evolution and ectodermal-specific expression of presumptive BDS toxin cDNAs from Anemonia viridis.

PubMed

Nicosia, Aldo; Maggio, Teresa; Mazzola, Salvatore; Cuttitta, Angela

2013-10-30

Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the β-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple-stranded antiparallel β-sheet and an additional small antiparallel β-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded β-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our cDNA libraries. The calculation of the relative abundance of BDS transcripts in the cDNA libraries revealed that BDS-1, BDS-3, BDS-4, BDS-5 and BDS-6 are the most represented transcripts.

A rare case of congenital epidermoid cyst of the hard palate

PubMed Central

Montebugnoli, Lucio; Tiberio, Cristiana; Venturi, Mattia

2011-01-01

Epidermoid cysts are benign conditions that are thought to derive from abnormally situated ectodermal inclusions in the oral cavity. They are generally found in hands, fingers, feet, ovaries and testicles but in oral cavity they represent a very rare event. This is the first case of an intraosseous epidermoid cyst situated in the hard palate. Healing was uneventful and there was no sign of recurrence in 2-years follow-up. PMID:22675054

The formation of endoderm-derived taste sensory organs requires a Pax9-dependent expansion of embryonic taste bud progenitor cells.

PubMed

Kist, Ralf; Watson, Michelle; Crosier, Moira; Robinson, Max; Fuchs, Jennifer; Reichelt, Julia; Peters, Heiko

2014-10-01

In mammals, taste buds develop in different regions of the oral cavity. Small epithelial protrusions form fungiform papillae on the ectoderm-derived dorsum of the tongue and contain one or few taste buds, while taste buds in the soft palate develop without distinct papilla structures. In contrast, the endoderm-derived circumvallate and foliate papillae located at the back of the tongue contain a large number of taste buds. These taste buds cluster in deep epithelial trenches, which are generated by intercalating a period of epithelial growth between initial placode formation and conversion of epithelial cells into sensory cells. How epithelial trench formation is genetically regulated during development is largely unknown. Here we show that Pax9 acts upstream of Pax1 and Sox9 in the expanding taste progenitor field of the mouse circumvallate papilla. While a reduced number of taste buds develop in a growth-retarded circumvallate papilla of Pax1 mutant mice, its development arrests completely in Pax9-deficient mice. In addition, the Pax9 mutant circumvallate papilla trenches lack expression of K8 and Prox1 in the taste bud progenitor cells, and gradually differentiate into an epidermal-like epithelium. We also demonstrate that taste placodes of the soft palate develop through a Pax9-dependent induction. Unexpectedly, Pax9 is dispensable for patterning, morphogenesis and maintenance of taste buds that develop in ectoderm-derived fungiform papillae. Collectively, our data reveal an endoderm-specific developmental program for the formation of taste buds and their associated papilla structures. In this pathway, Pax9 is essential to generate a pool of taste bud progenitors and to maintain their competence towards prosensory cell fate induction.

An essential role of variant histone H3.3 for ectomesenchyme potential of the cranial neural crest.

PubMed

Cox, Samuel G; Kim, Hyunjung; Garnett, Aaron Timothy; Medeiros, Daniel Meulemans; An, Woojin; Crump, J Gage

2012-09-01

The neural crest (NC) is a vertebrate-specific cell population that exhibits remarkable multipotency. Although derived from the neural plate border (NPB) ectoderm, cranial NC (CNC) cells contribute not only to the peripheral nervous system but also to the ectomesenchymal precursors of the head skeleton. To date, the developmental basis for such broad potential has remained elusive. Here, we show that the replacement histone H3.3 is essential during early CNC development for these cells to generate ectomesenchyme and head pigment precursors. In a forward genetic screen in zebrafish, we identified a dominant D123N mutation in h3f3a, one of five zebrafish variant histone H3.3 genes, that eliminates the CNC-derived head skeleton and a subset of pigment cells yet leaves other CNC derivatives and trunk NC intact. Analyses of nucleosome assembly indicate that mutant D123N H3.3 interferes with H3.3 nucleosomal incorporation by forming aberrant H3 homodimers. Consistent with CNC defects arising from insufficient H3.3 incorporation into chromatin, supplying exogenous wild-type H3.3 rescues head skeletal development in mutants. Surprisingly, embryo-wide expression of dominant mutant H3.3 had little effect on embryonic development outside CNC, indicating an unexpectedly specific sensitivity of CNC to defects in H3.3 incorporation. Whereas previous studies had implicated H3.3 in large-scale histone replacement events that generate totipotency during germ line development, our work has revealed an additional role of H3.3 in the broad potential of the ectoderm-derived CNC, including the ability to make the mesoderm-like ectomesenchymal precursors of the head skeleton.

An Essential Role of Variant Histone H3.3 for Ectomesenchyme Potential of the Cranial Neural Crest

PubMed Central

Cox, Samuel G.; Kim, Hyunjung; Garnett, Aaron Timothy; Medeiros, Daniel Meulemans; An, Woojin; Crump, J. Gage

2012-01-01

The neural crest (NC) is a vertebrate-specific cell population that exhibits remarkable multipotency. Although derived from the neural plate border (NPB) ectoderm, cranial NC (CNC) cells contribute not only to the peripheral nervous system but also to the ectomesenchymal precursors of the head skeleton. To date, the developmental basis for such broad potential has remained elusive. Here, we show that the replacement histone H3.3 is essential during early CNC development for these cells to generate ectomesenchyme and head pigment precursors. In a forward genetic screen in zebrafish, we identified a dominant D123N mutation in h3f3a, one of five zebrafish variant histone H3.3 genes, that eliminates the CNC–derived head skeleton and a subset of pigment cells yet leaves other CNC derivatives and trunk NC intact. Analyses of nucleosome assembly indicate that mutant D123N H3.3 interferes with H3.3 nucleosomal incorporation by forming aberrant H3 homodimers. Consistent with CNC defects arising from insufficient H3.3 incorporation into chromatin, supplying exogenous wild-type H3.3 rescues head skeletal development in mutants. Surprisingly, embryo-wide expression of dominant mutant H3.3 had little effect on embryonic development outside CNC, indicating an unexpectedly specific sensitivity of CNC to defects in H3.3 incorporation. Whereas previous studies had implicated H3.3 in large-scale histone replacement events that generate totipotency during germ line development, our work has revealed an additional role of H3.3 in the broad potential of the ectoderm-derived CNC, including the ability to make the mesoderm-like ectomesenchymal precursors of the head skeleton. PMID:23028350

p63 in skin development and ectodermal dysplasias

PubMed Central

Koster, Maranke I.

2010-01-01

The transcription factor p63 is critically important for skin development and maintenance. Processes that require p63 include epidermal lineage commitment, epidermal differentiation, cell adhesion, and basement membrane formation. Not surprisingly, alterations in the p63 pathway underlie a subset of ectodermal dysplasias, developmental syndromes in which the skin and skin appendages do not develop normally. This review summarizes the current understanding of the role of p63 in normal development and ectodermal dysplasias. PMID:20445549

Ectoderm gene activation in sea urchin embryos mediated by the CCAAT-binding factor.

PubMed

Li, Xiaotao; Bhattacharya, Chitralekha; Dayal, Sandeep; Maity, Sankar; Klein, William H

2002-05-01

Transcriptional enhancers are short stretches of DNA that function to achieve highly specific patterns of gene expression. To identify the mechanisms by which enhancers achieve their specificity, we made use of an enhancer from the aboral ectoderm-specific spec2a gene of the sea urchin Strongylocentrotus purpuratus. The spec2a enhancer contains five cis-regulatory elements within 78 base pairs that interact with five distinct DNA-binding proteins to confer aboral ectoderm expression. Here, we present an analysis of the sea urchin CCAAT binding factor (CBF), which binds to a CCAAT motif within the spec2a enhancer. S. purpuratus CBF and SpOtx, a ubiquitously expressed factor, act together at closely placed cis-regulatory elements to mediate spec2a transcription in the ectoderm. SpCBF was the sole factor that bound to the spec2a CCAAT element, and two of the three subunits that make up the CBF holoprotein were cloned and shown to have high sequence conservation with their vertebrate orthologs. Based on its involvement in the regulation of several other sea urchin genes, SpCBF appears to be a major transcription factor in the sea urchin embryo for positive regulation of ectoderm gene expression. In addition to its role in vertebrate cell growth and proliferation, our results indicate that CBF also functions at the early stages of germ layer formation, namely ectoderm differentiation.

Odonto-onycho-dermal dysplasia in a patient homozygous for a WNT10A nonsense mutation and mild manifestations of ectodermal dysplasia in carriers of the mutation.

PubMed

Krøigård, Anne Bruun; Clemmensen, Ole; Gjørup, Hans; Hertz, Jens Michael; Bygum, Anette

2016-03-10

Odonto-onycho-dermal dysplasia (OODD) is a rare form of ectodermal dysplasia characterized by severe oligodontia, onychodysplasia, palmoplantar hyperkeratosis, dry skin, hypotrichosis, and hyperhidrosis of the palms and soles. The ectodermal dysplasias resulting from biallelic mutations in the WNT10A gene result in highly variable phenotypes, ranging from isolated tooth agenesis to OODD and Schöpf-Schulz-Passarge syndrome (SSPS). We identified a female patient, with consanguineous parents, who was clinically diagnosed with OODD. Genetic testing showed that she was homozygous for a previously reported pathogenic mutation in the WNT10A gene, c.321C > A, p.Cys107*. The skin and nail abnormalities were for many years interpreted as psoriasis and treated accordingly. A thorough clinical examination revealed hypotrichosis and hyperhidrosis of the soles and dental examination revealed agenesis of permanent teeth except the two maxillary central incisors. Skin biopsies from the hyperkeratotic palms and soles showed the characteristic changes of eccrine syringofibroadenomatosis, which has been described in patients with ectodermal dysplasias. Together with a family history of tooth anomalies, this lead to the clinical suspicion of a hereditary ectodermal dysplasia. This case illustrates the challenges of diagnosing ectodermal dysplasia like OODD and highlights the relevance of interdisciplinary cooperation in the diagnosis of rare conditions.

Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency.

PubMed

Bergendal, Birgitta; Norderyd, Johanna; Zhou, Xiaolei; Klar, Joakim; Dahl, Niklas

2016-11-24

The WNT10A protein is critical for the development of ectodermal appendages. Variants in the WNT10A gene may be associated with a spectrum of ectodermal abnormalities including extensive tooth agenesis. In seven patients with severe tooth agenesis we identified anomalies in primary dentition and additional ectodermal symptoms, and assessed WNT10A mutations by genetic analysis. Investigation of primary dentition revealed peg-shaped crowns of primary mandibular incisors and three individuals had agenesis of at least two primary teeth. The permanent dentition was severely affected in all individuals with a mean of 21 missing teeth. Primary teeth were most often present in positions were succedaneous teeth were missing. Furthermore, most existing molars had taurodontism. Light, brittle or coarse hair was reported in all seven individuals, hyperhidrosis of palms and soles in six individuals and nail anomalies in two individuals. The anomalies in primary dentition preceded most of the additional ectodermal symptoms. Genetic analysis revealed that all seven individuals were homozygous or compound heterozygous for WNT10A mutations resulting in C107X, E222X and F228I. We conclude that tooth agenesis and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of permanent dentition as well as ectodermal symptoms of varying severity may be predictors of bi-allelic WNT10A mutations of importance for diagnosis, counselling and follow-up.

Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues.

PubMed

De Castro, Sandra C P; Hirst, Caroline S; Savery, Dawn; Rolo, Ana; Lickert, Heiko; Andersen, Bogi; Copp, Andrew J; Greene, Nicholas D E

2018-03-15

Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

ΔNp63 is an ectodermal gatekeeper of epidermal morphogenesis

PubMed Central

Shalom-Feuerstein, R; Lena, A M; Zhou, H; De La Forest Divonne, S; Van Bokhoven, H; Candi, E; Melino, G; Aberdam, D

2011-01-01

p63, a member of p53 family, has a significant role in the development and maintenance of stratified epithelia. However, a persistent dispute remained over the last decade concerning the interpretation of the severe failure of p63-null embryos to develop stratified epithelia. In this study, by investigating both p63-deficient strains, we demonstrated that p63-deficient epithelia failed to develop beyond ectodermal stage as they remained a monolayer of non-proliferating cells expressing K8/K18. Importantly, in the absence of p63, corneal-epithelial commitment (which occurs at embryonic day 12.5 of mouse embryogenesis) was hampered 3 weeks before corneal stem cell renewal (that begins at P14). Taken together, these data illustrate the significant role of p63 in epithelial embryogenesis, before and independently of other functions of p63 in adult stem cells regulation. Transcriptome analysis of laser captured-embryonic tissues confirmed the latter hypothesis, demonstrating that a battery of epidermal genes that were activated in wild-type epidermis remained silent in p63-null tissues. Furthermore, we defined a subset of novel bona fide p63-induced genes orchestrating first epidermal stratification and a subset of p63-repressed mesodermal-specific genes. These data highlight the earliest recognized action of ΔNp63 in the induction epidermal morphogenesis at E11.5. In the absence of p63, a mesodermal program is activated while epidermal morphogenesis does not initiate. PMID:21127502

Analysis of the hypoxia-sensing pathway in Drosophila melanogaster

PubMed Central

Arquier, Nathalie; Vigne, Paul; Duplan, Eric; Hsu, Tien; Therond, Pascal P.; Frelin, Christian; D'Angelo, Gisela

2005-01-01

The mechanism by which hypoxia induces gene transcription involves the inhibition of HIF-1α (hypoxia-inducible factor-1 α subunit) PHD (prolyl hydroxylase) activity, which prevents the VHL (von Hippel-Lindau)-dependent targeting of HIF-1α to the ubiquitin/proteasome pathway. HIF-1α thus accumulates and promotes gene transcription. In the present study, first we provide direct biochemical evidence for the presence of a conserved hypoxic signalling pathway in Drosophila melanogaster. An assay for 2-oxoglutarate-dependent dioxygenases was developed using Drosophila embryonic and larval homogenates as a source of enzyme. Drosophila PHD has a low substrate specificity and hydroxylates key proline residues in the ODD (oxygen-dependent degradation) domains of human HIF-1α and Similar, the Drosophila homologue of HIF-1α. The enzyme promotes human and Drosophila [35S]VHL binding to GST (glutathione S-transferase)–ODD-domain fusion protein. Hydroxylation is enhanced by proteasomal inhibitors and was ascertained using an anti-hydroxyproline antibody. Secondly, by using transgenic flies expressing a fusion protein that combined an ODD domain and the green fluorescent protein (ODD–GFP), we analysed the hypoxic cascade in different embryonic and larval tissues. Hypoxic accumulation of the reporter protein was observed in the whole tracheal tree, but not in the ectoderm. Hypoxic stabilization of ODD–GFP in the ectoderm was restored by inducing VHL expression in these cells. These results show that Drosophila tissues exhibit different sensitivities to hypoxia. PMID:16176182

AKT signaling displays multifaceted functions in neural crest development.

PubMed

Sittewelle, Méghane; Monsoro-Burq, Anne H

2018-05-31

AKT signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. Alterations impacting the AKT pathway are involved in many pathological conditions in human disease. Similarly, during development, multiple transmembrane molecules, such as FGF receptors, PDGF receptors or integrins, activate AKT to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions. While many studies in mouse embryos have clearly implicated AKT signaling in the differentiation of several neural crest derivatives, information on AKT functions during the earliest steps of neural crest development had remained relatively scarce until recently. However, recent studies on known and novel regulators of AKT signaling demonstrate that this pathway plays critical roles throughout the development of neural crest progenitors. Non-mammalian models such as fish and frog embryos have been instrumental to our understanding of AKT functions in neural crest development, both in neural crest progenitors and in the neighboring tissues. This review combines current knowledge acquired from all these different vertebrate animal models to describe the various roles of AKT signaling related to neural crest development in vivo. We first describe the importance of AKT signaling in patterning the tissues involved in neural crest induction, namely the dorsal mesoderm and the ectoderm. We then focus on AKT signaling functions in neural crest migration and differentiation. Copyright © 2018 Elsevier Inc. All rights reserved.

Cell proliferation in mammalian gastrulation: the ventral node and notochord are relatively quiescent.

PubMed

Bellomo, D; Lander, A; Harragan, I; Brown, N A

1996-04-01

During gastrulation, the node of the mammalian embryo appears to be an organising centre, homologous to Hensen's node in the chick and the dorsal lip of the amphibian blastopore. In addition, the node serves as a precursor population for the head process, notochord and foregut endoderm. We have studied node architecture and cell morphology by electron microscopy, and cell proliferation using bromodeoxyuridine incorporation and mitotic counts. The dorsal (ectodermal) and ventral (endodermal) components of the node are two distinct populations, separated by a basement membrane. The ventral node, contiguous with the head process, is characterised by a relatively low proliferation rate, with only approximately 10% of cells incorporating BrdU over 4 hr, compared to > 95% in surrounding mesodermal and ectodermal tissues. This is the case from the beginning of node formation, at the no-allantoic-bud stage, until the 7 somite stage, and is not compatible with the idea that the ventral node is a stem cell population. The dorsal node is highly proliferative, its rate of division being indistinguishable from the neurectoderm, with which it is contiguous. In the ventral node, two regions can be recognised: cells in the "pit" are columnar and all monociliated; around them lies a "crown" of cells arranged radially in a horseshoe shape and less often ciliated. Node derivatives share common features with the ventral node; the head process and the notochord are relatively quiescent; and some head process cells are also monociliated. Node and head process monocilia are immotile and appear to be associated with non-proliferation. We suggest that the ventral node contains all the properties of the organiser, while the dorsal node is indistinct from the surrounding epiblast. The cranial end of the foregut pouch, the thyroid diverticulum, and the promyocardium of early somite stage embryos are also areas of low cell division. All the described regions of relative quiescence are sites of expression of members of the TGF beta family, which may be involved in maintaining non-proliferation.

Hypohidrotic ectodermal dysplasia with ankylosis of temporomandibular joint and cleft palate: A rare presentation

PubMed Central

Goyal, Manisha; Pradhan, Gaurav; Gupta, Sunita; Kapoor, Seema

2015-01-01

The ectodermal dysplasias are a heterogenous group of diseases, which have one or more anomalies of the hair, teeth, nails, and sweat glands. Hypohidrotic ectodermal dysplasia (HED) is the most common type and is usually transmitted as an X-linked recessive trait. It is characterized by classical triad of hypotrichosis, anhidrosis/hypohidrosis, and hypodontia/anodontia. Here, we describe an Indian boy affected with HED and rare features including ankylosis of temporomandibular joint and cleft palate. PMID:25684924

Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development.

PubMed

Manthey, Abby L; Lachke, Salil A; FitzGerald, Paul G; Mason, Robert W; Scheiblin, David A; McDonald, John H; Duncan, Melinda K

2014-02-01

SIP1 encodes a DNA-binding transcription factor that regulates multiple developmental processes, as highlighted by the pleiotropic defects observed in Mowat-Wilson syndrome, which results from mutations in this gene. Further, in adults, dysregulated SIP1 expression has been implicated in both cancer and fibrotic diseases, where it functionally links TGFβ signaling to the loss of epithelial cell characteristics and gene expression. In the ocular lens, an epithelial tissue important for vision, Sip1 is co-expressed with epithelial markers, such as E-cadherin, and is required for the complete separation of the lens vesicle from the head ectoderm during early ocular morphogenesis. However, the function of Sip1 after early lens morphogenesis is still unknown. Here, we conditionally deleted Sip1 from the developing mouse lens shortly after lens vesicle closure, leading to defects in coordinated fiber cell tip migration, defective suture formation, and cataract. Interestingly, RNA-Sequencing analysis on Sip1 knockout lenses identified 190 differentially expressed genes, all of which are distinct from previously described Sip1 target genes. Furthermore, 34% of the genes with increased expression in the Sip1 knockout lenses are normally downregulated as the lens transitions from the lens vesicle to early lens, while 49% of the genes with decreased expression in the Sip1 knockout lenses are normally upregulated during early lens development. Overall, these data imply that Sip1 plays a major role in reprogramming the lens vesicle away from a surface ectoderm cell fate towards that necessary for the development of a transparent lens and demonstrate that Sip1 regulates distinctly different sets of genes in different cellular contexts. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development

PubMed Central

Manthey, Abby L.; Lachke, Salil A.; FitzGerald, Paul G.; Mason, Robert W.; Scheiblin, David A.; McDonald, John H.; Duncan, Melinda K.

2014-01-01

SIP1 encodes a DNA-binding transcription factor that regulates multiple developmental processes, as highlighted by the pleiotropic defects observed in Mowat-Wilson Syndrome, which results from mutations in this gene. Further, in adults, dysregulated SIP1 expression has been implicated in both cancer and fibrotic diseases, where it functionally links TGFβ signaling to the loss of epithelial cell characteristics and gene expression. In the ocular lens, an epithelial tissue important for vision, Sip1 is co-expressed with epithelial markers, such as E-cadherin, and is required for the complete separation of the lens vesicle from the head ectoderm during early ocular morphogenesis. However, the function of Sip1 after early lens morphogenesis is still unknown. Here, we conditionally deleted Sip1 from the developing mouse lens shortly after lens vesicle closure, leading to defects in coordinated fiber cell tip migration, defective suture formation, and cataract. Interestingly, RNA-Sequencing analysis on Sip1 knockout lenses identified 190 differentially expressed genes, all of which are distinct from previously described Sip1 target genes. Furthermore, 34% of the genes with increased expression in the Sip1 knockout lenses are normally downregulated as the lens transitions from the lens vesicle to early lens, while 49% of the genes with decreased expression in the Sip1 knockout lenses are normally upregulated during early lens development. Overall, these data imply that Sip1 plays a major role in reprogramming the lens vesicle away from a surface ectoderm cell fate towards that necessary for the development of a transparent lens and demonstrate that Sip1 regulates distinctly different sets of genes in different cellular contexts. PMID:24161570

Anesthetic management of a pediatric patient with hypohidrotic ectodermal dysplasia undergoing emergency surgery.

PubMed

Ahiskalioglu, Elif Oral; Ahiskalioglu, Ali; Firinci, Binali; Dostbil, Aysenur; Aksoy, Mehmet

2015-01-01

Ectodermal dysplasias are rare conditions with a triad of hypotrichosis, anodontia and anhidrosis. In literature review there have been only a few reports of anesthetic management of patients with ectodermal dysplasias. Hyperthermia is a very serious risk which may occur due to the defect of sweat glands. The present case involves a 10-year-old child with ectodermal dysplasia who presented with an acute abdomen and was considered for an emergency surgery. Our aim was to demonstrate the successful management of this case using a combination of general and epidural anesthesia. It is important for anesthesiologist to have information about this syndrome in case of emergency operations, since it can prevent serious complications and even save lives. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

The management of ectodermal dysplasia and severe hypodontia. International conference statements.

PubMed

Hobkirk, J A; Nohl, F; Bergendal, B; Storhaug, K; Richter, M K

2006-09-01

An international conference on ectodermal dysplasias and hypodontia, held in London in 2004, featured a session devoted to the management of the ectodermal dysplasias and severe hypodontia. This paper presents a set of statements prepared by an international specialist panel, including representatives of patient support groups, who presented and subsequently debated a series of papers on this subject. The following topics were explored: potential roles of patient support groups; core care standards, including the roles and composition of medical and dental multidisciplinary teams for treating these conditions; the format of a baseline data set for patients with an ED; and priorities for research in ectodermal dysplasias, with particular regard to laboratory and clinical studies, and research methodology. The statements are intended to form an international framework for developing patient care pathways, and collaborative research in this field.

An evaluation of clinical, radiological and three-dimensional dental tomography findings in ectodermal dysplasia cases

PubMed Central

Doğan, Mehmet-Sinan; Callea, Michele; Aksoy, Orhan; Clarich, Gabriella; Günay, Ayşe; Günay, Ahmet; Güven, Sedat; Maglione, Michele; Akkuş, Zeki

2015-01-01

Background This study aimed to review the results related to head and jaw disorders in cases of ectodermal dysplasia. The evaluation of ectodermal dysplasia cases was made by clincal examination and examination of the jaw and facial areas radiologically and on cone-beam 3-dimensional dental tomography (CBCT) images. Material and Methods In the 36 cases evaluated in the study, typical clinical findings of pure hypohidrotic ectodermal displasia (HED) were seen, such as missing teeth, dry skin, hair and nail disorders. CBCT images were obtained from 12 of the 36 cases, aged 1.5- 45 years, and orthodontic analyses were made on these images. Results The clinical and radiological evaluations determined, hypodontia or oligodontia, breathing problems, sweating problems, a history of fever, sparse hair, saddle nose, skin peeling, hypopigmentation, hyperpigmentation, finger and nail deformities, conical teeth anomalies, abnormal tooth root formation, tooth resorption in the root, gingivitis, history of epilepsy, absent lachrymal canals and vision problems in the cases which included to the study. Conclusions Ectodermal dysplasia cases have a particular place in dentistry and require a professional, multi-disciplinary approach in respect of the chewing function, orthognathic problems, growth, oral and dental health. It has been understood that with data obtained from modern technologies such as three-dimensional dental tomography and the treatments applied, the quality of life of these cases can be improved. Key words: Ectodermal dysplasia, three-dimensional dental tomography. PMID:25662550

DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers

PubMed Central

Isagawa, Takayuki; Nagae, Genta; Shiraki, Nobuaki; Fujita, Takanori; Sato, Noriko; Ishikawa, Shumpei; Kume, Shoen; Aburatani, Hiroyuki

2011-01-01

Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes. PMID:22016810

DNA methylation profiling of embryonic stem cell differentiation into the three germ layers.

PubMed

Isagawa, Takayuki; Nagae, Genta; Shiraki, Nobuaki; Fujita, Takanori; Sato, Noriko; Ishikawa, Shumpei; Kume, Shoen; Aburatani, Hiroyuki

2011-01-01

Embryogenesis is tightly regulated by multiple levels of epigenetic regulation such as DNA methylation, histone modification, and chromatin remodeling. DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization. Subsequent developmental reprogramming occurs by de novo methylation and demethylation. Variance in DNA methylation patterns between different cell types is not well understood. Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analyzed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm). Most of the methylated regions are methylated across all three germ layers and in the three adult somatic tissues. This commonly methylated gene set is enriched in germ cell-associated genes that are generally transcriptionally inactive in somatic cells. We also compared DNA methylation patterns by global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation. Our combined findings indicate that differentiation of ES cells into the three germ layers is accompanied by an increased number of commonly methylated DNA regions and that these tissue-specific alterations in methylation occur for only a small number of genes. DNA methylation at the proximal promoter regions of commonly methylated genes thus appears to be an irreversible mark which functions to fix somatic lineage by repressing the transcription of germ cell-specific genes.

The pre-vertebrate origins of neurogenic placodes.

PubMed

Abitua, Philip Barron; Gainous, T Blair; Kaczmarczyk, Angela N; Winchell, Christopher J; Hudson, Clare; Kamata, Kaori; Nakagawa, Masashi; Tsuda, Motoyuki; Kusakabe, Takehiro G; Levine, Michael

2015-08-27

The sudden appearance of the neural crest and neurogenic placodes in early branching vertebrates has puzzled biologists for over a century. These embryonic tissues contribute to the development of the cranium and associated sensory organs, which were crucial for the evolution of the vertebrate "new head". A previous study suggests that rudimentary neural crest cells existed in ancestral chordates. However, the evolutionary origins of neurogenic placodes have remained obscure owing to a paucity of embryonic data from tunicates, the closest living relatives to those early vertebrates. Here we show that the tunicate Ciona intestinalis exhibits a proto-placodal ectoderm (PPE) that requires inhibition of bone morphogenetic protein (BMP) and expresses the key regulatory determinant Six1/2 and its co-factor Eya, a developmental process conserved across vertebrates. The Ciona PPE is shown to produce ciliated neurons that express genes for gonadotropin-releasing hormone (GnRH), a G-protein-coupled receptor for relaxin-3 (RXFP3) and a functional cyclic nucleotide-gated channel (CNGA), which suggests dual chemosensory and neurosecretory activities. These observations provide evidence that Ciona has a neurogenic proto-placode, which forms neurons that appear to be related to those derived from the olfactory placode and hypothalamic neurons of vertebrates. We discuss the possibility that the PPE-derived GnRH neurons of Ciona resemble an ancestral cell type, a progenitor to the complex neuronal circuit that integrates sensory information and neuroendocrine functions in vertebrates.

Shaping sound in space: the regulation of inner ear patterning.

PubMed

Groves, Andrew K; Fekete, Donna M

2012-01-01

The inner ear is one of the most morphologically elaborate tissues in vertebrates, containing a group of mechanosensitive sensory organs that mediate hearing and balance. These organs are arranged precisely in space and contain intricately patterned sensory epithelia. Here, we review recent studies of inner ear development and patterning which reveal that multiple stages of ear development - ranging from its early induction from the embryonic ectoderm to the establishment of the three cardinal axes and the fine-grained arrangement of sensory cells - are orchestrated by gradients of signaling molecules.

Shaping sound in space: the regulation of inner ear patterning

PubMed Central

Groves, Andrew K.; Fekete, Donna M.

2012-01-01

The inner ear is one of the most morphologically elaborate tissues in vertebrates, containing a group of mechanosensitive sensory organs that mediate hearing and balance. These organs are arranged precisely in space and contain intricately patterned sensory epithelia. Here, we review recent studies of inner ear development and patterning which reveal that multiple stages of ear development – ranging from its early induction from the embryonic ectoderm to the establishment of the three cardinal axes and the fine-grained arrangement of sensory cells – are orchestrated by gradients of signaling molecules. PMID:22186725

Ectrodactyly, Ectodermal dysplasia, and Cleft Lip-Palate Syndrome; Its Association with Conductive Hearing Loss

ERIC Educational Resources Information Center

Robinson, Geoffrey C.; And Others

1973-01-01

Conductive hearing loss associated with the ectrodactyly, ectodermal dysplasia, and cleft lip palate syndrome was reported in one sporadic case and in a pedigree with four cases in three generations. (GW)

Sox5 is a DNA binding co-factor for BMP R-Smads that directs target specificity during patterning of the early ectoderm

PubMed Central

Nordin, Kara; LaBonne, Carole

2014-01-01

SUMMARY The SoxD factor, Sox5, is expressed in ectodermal cells at times and places where BMP signaling is active, including the cells of the animal hemisphere at blastula stages, and the neural plate border (NPB) and neural crest (NC) at neurula stages. Sox5 is required for proper ectoderm development, and deficient embryos display patterning defects characteristic of perturbations of BMP signaling, including loss of neural crest and epidermis and expansion of the neural plate. We show that Sox5 is essential for activation of BMP target genes in embryos and explants, that it physically interacts with BMP R-Smads, and that it is essential for recruitment of Smad1/4 to BMP regulatory elements. Our findings identify Sox5 as the long sought DNA binding partner for BMP R-Smads essential to plasticity and pattern in the early ectoderm. PMID:25453832

A case of probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis.

PubMed

Argenziano, G; Monsurrò, M R; Pazienza, R; Delfino, M

1998-02-01

We describe a woman with a probable autosomal recessive ectodermal dysplasia with corkscrew hairs and mental retardation in a family with tuberous sclerosis. Other findings included syndactyly, typical facies, dental abnormalities, dermatoglyphic hypoplasia, epidermal ridge sweat pore count slightly below normal, and keratosis pilaris. Clinical studies and genetic analysis excluded the diagnosis of tuberous sclerosis in our patient. We conclude that she has ectodermal dysplasia associated with mental retardation. This association has been described previously; it suggests the possible interrelationship of a community of ectodermal dysplasia syndromes with a distinctive structural hair abnormality (pili torti et canaliculi), variable midfacial malformations, limb defects, and other features such as mental retardation. The similarity of our patient to that described by Whiting et al. and Abramovits-Ackerman et al. suggests the autonomy of this syndrome.

Ectodysplasin A Pathway Contributes to Human and Murine Skin Repair.

PubMed

Garcin, Clare L; Huttner, Kenneth M; Kirby, Neil; Schneider, Pascal; Hardman, Matthew J

2016-05-01

The highly conserved ectodysplasin A (EDA)/EDA receptor signaling pathway is critical during development for the formation of skin appendages. Mutations in genes encoding components of the EDA pathway disrupt normal appendage development, leading to the human disorder hypohidrotic ectodermal dysplasia. Spontaneous mutations in the murine Eda (Tabby) phenocopy human X-linked hypohidrotic ectodermal dysplasia. Little is known about the role of EDA signaling in adult skin homeostasis or repair. Because wound healing largely mimics the morphogenic events that occur during development, we propose a role for EDA signaling in adult wound repair. Here we report a pronounced delay in healing in Tabby mice, demonstrating a functional role for EDA signaling in adult skin. Moreover, pharmacological activation of the EDA pathway in both Tabby and wild-type mice significantly accelerates healing, influencing multiple processes including re-epithelialization and granulation tissue matrix deposition. Finally, we show that the healing promoting effects of EDA receptor activation are conserved in human skin repair. Thus, targeted manipulation of the EDA/EDA receptor pathway has clear therapeutic potential for the future treatment of human pathological wound healing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Deletion of OTX2 in neural ectoderm delays anterior pituitary development

PubMed Central

Mortensen, Amanda H.; Schade, Vanessa; Lamonerie, Thomas; Camper, Sally A.

2015-01-01

OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the pituitary defects, we used different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. Mice homozygous for Otx2 deficiency in early head development and pituitary oral ectoderm exhibit craniofacial defects and pituitary gland dysmorphology, but normal pituitary cell specification. The morphological defects mimic those observed in humans and mice with OTX2 heterozygous mutations. Mice homozygous for Otx2 deficiency in the pituitary neural ectoderm exhibited altered patterning of gene expression and ablation of FGF signaling. The posterior pituitary lobe and stalk, which normally arise from neural ectoderm, were extremely hypoplastic. Otx2 expression was intact in Rathke's pouch, the precursor to the anterior lobe, but the anterior lobe was hypoplastic. The lack of FGF signaling from the neural ectoderm was sufficient to impair anterior lobe growth, but not the differentiation of hormone-producing cells. This study demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe and pituitary stalk, and it has significant extrinsic effects on anterior pituitary growth. Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. PMID:25315894

Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate-ectodermal dysplasia syndrome in an Asian patient.

PubMed

Yoshida, Kazue; Hayashi, Ryota; Fujita, Hideki; Kubota, Masaya; Kondo, Mai; Shimomura, Yutaka; Niizeki, Hironori

2015-07-01

Cleft lip/palate-ectodermal dysplasia syndrome is a rare, autosomal recessive disorder caused by homozygous loss-of-function mutations of the poliovirus receptor-like 1 (PVRL1) gene encoding nectin-1. Nectin-1 is a cell-cell adhesion molecule that is important for the initial step in the formation of adherens junctions and tight junctions; it is expressed in keratinocytes, neurons, and the developing face and palate. Clinical manifestations comprise a unique facial appearance with cleft lip/palate, ectodermal dysplasia, cutaneous syndactyly of the fingers and/or toes, and in some cases, mental retardation. We present the first report, to our knowledge, of an Asian individual with cleft lip/palate-ectodermal dysplasia syndrome with a novel PVRL1 mutation. A 7-year-old Japanese boy, the first child of a consanguineous marriage, showed hypohidrotic ectodermal dysplasia with sparse, brittle, fine, dry hair and hypodontia, the unique facial appearance with cleft lip/palate, cutaneous syndactyly of the fingers and mild mental retardation. Scanning electron microscopic examination of the hair demonstrated pili torti and pili trianguli et canaliculi. Mutation analysis of exon 2 of PVRL1 revealed a novel homozygous nonsense mutation, c.400C>T (p.Arg134*). His parents were heterozygous for the mutant alleles. All four PVRL1 mutations identified in cleft lip/palate-ectodermal dysplasia syndrome to date, including this study, resulted in truncated proteins that lack the transmembrane domain and intracellular domain of nectin-1, which is necessary to initiate the cell-cell adhesion process. © 2015 Japanese Dermatological Association.

Engineering stromal-epithelial interactions in vitro for ...

EPA Pesticide Factsheets

Background: Crosstalk between epithelial and stromal cells drives the morphogenesis of ectodermal organs during development and promotes normal mature adult epithelial tissue function. Epithelial-mesenchymal interactions (EMIs) have been examined using mammalian models, ex vivo tissue recombination, and in vitro co-cultures. Although these approaches have elucidated signaling mechanisms underlying morphogenetic processes and adult mammalian epithelial tissue function, they are limited by the availability of human tissue, low throughput, and human developmental or physiological relevance. Objectives: Bioengineering strategies to promote EMIs using human epithelial and mesenchymal cells have enabled the development of human in vitro models of adult epidermal and glandular tissues. In this review, we describe recent bioengineered models of human epithelial tissue and organs that can instruct the design of organotypic models of human developmental processes.Methods: We reviewed current bioengineering literature and here describe how bioengineered EMIs have enabled the development of human in vitro epithelial tissue models.Discussion: Engineered models to promote EMIs have recapitulated the architecture, phenotype, and function of adult human epithelial tissue, and similar engineering principles could be used to develop models of developmental morphogenesis. We describe how bioengineering strategies including bioprinting and spheroid culture could be implemented to

Two-tiered control of epithelial growth and autophagy by the insulin receptor and the ret-like receptor, stitcher.

PubMed

O'Farrell, Fergal; Wang, Shenqiu; Katheder, Nadja; Rusten, Tor Erik; Samakovlis, Christos

2013-07-01

Body size in Drosophila larvae, like in other animals, is controlled by nutrition. Nutrient restriction leads to catabolic responses in the majority of tissues, but the Drosophila mitotic imaginal discs continue growing. The nature of these differential control mechanisms that spare distinct tissues from starvation are poorly understood. Here, we reveal that the Ret-like receptor tyrosine kinase (RTK), Stitcher (Stit), is required for cell growth and proliferation through the PI3K-I/TORC1 pathway in the Drosophila wing disc. Both Stit and insulin receptor (InR) signaling activate PI3K-I and drive cellular proliferation and tissue growth. However, whereas optimal growth requires signaling from both InR and Stit, catabolic changes manifested by autophagy only occur when both signaling pathways are compromised. The combined activities of Stit and InR in ectodermal epithelial tissues provide an RTK-mediated, two-tiered reaction threshold to varying nutritional conditions that promote epithelial organ growth even at low levels of InR signaling.

Ovarian teratoma displaying a wide variety of tissue components in a broiler chicken (Gallus Domesticus): morphological heterogeneity of pluripotential germ cell during tumorigenesis.

PubMed

Ohfuji, S

2016-01-01

Spontaneous ovarian teratoma was found in a seven-week-old female Chunky broiler chicken that was slaughtered for food. On post-mortem inspection, a spherical tumor mass attaching to a juvenile ovary was found in the abdominal cavity. Histopathologically, the tumor was comprised of immature mesenchymal stroma and a variety of mature tissue elements of mesodermal and ectodermal origin. In addition, there were multiple indistinguishable tissue elements, which showed no malignant cytological features but were unidentifiable as to corresponding embryological layer of origin. These heterogeneous teratoma tissues consisted of a variety of glandular, cystic, duct-like, and tubular structures, some of which exhibited a lining by a mixture of both keratinizing/non-keratinizing stratified squamous epithelial cells and cuboidal/columnar epithelial cells. The ovarian tetatoma was considered a benign and congenital one. The highly diverse differentiation of the teratoma might have manifested a morphological aspect of intrinsic character of the pluripotential germ cells during tumorigenesis.

[Ectodermal Capdepont syndrome and oral prosthetic rehabilitation. About a clinical case].

PubMed

Kumpanya, P; Matshumba, M; Sekele, I B; Mayunga, M; Lutula, P S; Ntumba, M K

2015-03-01

The authors describe the ectodermal Capdepont syndrome as an anomaly characterized by anhidrosis, hypotrichosis and anodontia diagnosed in a 22 year-old adult. In front of this anodontia, oral prosthetic rehabilitation remains the only solution.

Phylostratigraphic profiles reveal a deep evolutionary history of the vertebrate head sensory systems

PubMed Central

2013-01-01

Background The vertebrate head is a highly derived trait with a heavy concentration of sophisticated sensory organs that allow complex behaviour in this lineage. The head sensory structures arise during vertebrate development from cranial placodes and the neural crest. It is generally thought that derivatives of these ectodermal embryonic tissues played a central role in the evolutionary transition at the onset of vertebrates. Despite the obvious importance of head sensory organs for vertebrate biology, their evolutionary history is still uncertain. Results To give a fresh perspective on the adaptive history of the vertebrate head sensory organs, we applied genomic phylostratigraphy to large-scale in situ expression data of the developing zebrafish Danio rerio. Contrary to traditional predictions, we found that dominant adaptive signals in the analyzed sensory structures largely precede the evolutionary advent of vertebrates. The leading adaptive signals at the bilaterian-chordate transition suggested that the visual system was the first sensory structure to evolve. The olfactory, vestibuloauditory, and lateral line sensory organs displayed a strong link with the urochordate-vertebrate ancestor. The only structures that qualified as genuine vertebrate innovations were the neural crest derivatives, trigeminal ganglion and adenohypophysis. We also found evidence that the cranial placodes evolved before the neural crest despite their proposed embryological relatedness. Conclusions Taken together, our findings reveal pre-vertebrate roots and a stepwise adaptive history of the vertebrate sensory systems. This study also underscores that large genomic and expression datasets are rich sources of macroevolutionary information that can be recovered by phylostratigraphic mining. PMID:23587066

[Clinicopathologic study of sinonasal teratocarcinosarcoma and its contrast with olfactory neuroblastoma].

PubMed

Li, Xue; Liu, Hong-Gang; Xie, Xin-Ji; Han, Yi-Ding; Li, Ming

2008-07-01

To study the clinicopathologic features, diagnosis and differential diagnosis of sinonasal teratocarcinosarcoma (SNTCS) and olfactory neuroblastoma (ONB), and to discuss the histogenesis and possible relationship between SNTCS and ONB. Seven cases of SNTCS and 34 cases of ONB were retrieved from the pathological archives together with one case each of malignant teratoma and immature embryonic tissue at 8 weeks were collected from Beijing Tongren Hospital. The clinicopathologic features were analyzed and immunohistochemical staining was performed on paraffin sections. Six of the SNTCS patients were male and one was female. The patients age range was 25 to 69 years (mean age 46). Four cases were initial presentation and three were recurrences. Histologically, the tumor shows multiple tissue components derived from three germ layers. There were mixture of teratoma-like tissue and carcinosarcoma. The components include fetal clear cell squamous epithelium derived from ectoderm. Glandular and tubular structures and ciliated columnar epithelium derived from endoderm. Fibroblasts, striated muscle, smooth muscle, cartilage and osteoid matrix derived from mesoderm. The carcinoma component exhibited mostly adenocarcinoma and squamous cell carcinoma, whereas the sarcoma component mostly exhibited rhabdomyosarcoma, leiomyosarcoma, and fibrosarcoma. In addition, carcinoid, and primitive mesenchymal tissue and the ONB component were also seen. The morphological characteristics of SNTCS comprised fetal clear cell squamous epithelium, carcinosarcoma and the ONB component. By immunohistochemistry, the epithelial component and cells with epithelium differentiation were positive for cytokeratin (pan) and EMA. The ONB component was positive for Syn, NSE, CD99, NF and CgA to different degrees. Neurofibril bundles were positive for S-100, and Flexner-Wintersteiner rosettes expressed cytokeratin (pan) and EMA. The spindle cells expressed vimentin, SMA, desmin, myosin and myoglobin. The primitive mesenchymal tissue expressed vimentin, and the mucoid materials and glycogen were positive for PAS. GFAP was negative in all cases. The 34 cases of ONB, included 18 men and 16 women, the age ranged from 12 to 72 years (mean 42.8 years). Microscopically, the tumor shows epithelial nests, net of angioma-like fibrous connective tissues, small round and spindle cells, glandular, squamous-like cells, and cells of rhabdomyoblastic differentiation, Homer-Wright and Flexner rosette, bundles of neurofibrils, etc. NSE and CgA were expressed in small cells. S-100 protein was positive in the areas of bunches of neurofibril. Cytokeratin (pan) was positive in epithelial cells. Myoglobin was positive in the cells of rhabdomyoblastic differentiation. The single case of immature malignant teratoma exhibited primitive nerve tissue, but fetal clear cell squamous epithelium was not found. In the immature embryonic tissue, rudimentary organs were formed, with fetal clear cell squamous epithelium lining present on the nasal and oral cavities surface. SNTCS is a rare and aggressive malignant neoplasm. Most of ONB are low-grade malignant tumors. Morphological differences are the most important basis to make differentiate SNTCS from ONB. As SNTCS may demonstrate a multiplicity of structures and pleomorphism, inadequate sampling at biopsy, therefore, may lead to errors in diagnosis. No evidence show that SNTCS are derived from germ cells and sinonasal teratoid carcinosarcoma may be a more proper name. SNTCS probably arises from primitive totipotential cells of olfactory/sinonasal membrane, and the relationship between SNTCS and ONB needs further study.

Cellular basis of gastrulation in the sand dollar Scaphechinus mirabilis.

PubMed

Kominami, T; Takata, H

2000-12-01

The processes of gastrulation in the sand dollar Scaphechinus mirabilis are quite different from those in regular echinoids. In this study, we explored the cellular basis of gastrulation in this species with several methods. Cell-tracing experiments revealed that the prospective endodermal cells were convoluted throughout the invagination processes. Histological observation showed that the ectodermal layer remained thickened, and the vegetal cells retained an elongated shape until the last step of invagination. Further, most of the vegetal ectodermal cells were skewed or distorted. Wedge-shaped cells were common in the vegetal ectoderm, especially at the subequatorial region. In these embryos, unlike the embryos of regular echinoids, secondary mesenchyme cells did not seem to exert the force to pull up the archenteron toward the inner surface of the apical plate. In fact, the archenteron cells were not stretched along the axis of elongation and were in close contact with each other. Here we found that gastrulation was completely blocked when the embryos were attached to a glass dish coated with poly-L-lysine, in which the movement of the ectodermal layer was inhibited. These results suggest that a force generated by the thickened ectoderm, rather than rearrangement of the archenteron cells, may play a key role in the archenteron elongation in S. mirabilis embryos.

Ectodermal dysplasias: a new clinical-genetic classification

PubMed Central

Priolo, M.; Lagana, C.

2001-01-01

The ectodermal dysplasias (EDs) are a large and complex nosological group of diseases, first described by Thurnam in 1848. In the last 10 years more than 170 different pathological clinical conditions have been recognised and defined as EDs, all sharing in common anomalies of the hair, teeth, nails, and sweat glands. Many are associated with anomalies in other organs and systems and, in some conditions, with mental retardation.
The anomalies affecting the epidermis and epidermal appendages are extremely variable and clinical overlap is present among the majority of EDs. Most EDs are defined by particular clinical signs (for example, eyelid adhesion in AEC syndrome, ectrodactyly in EEC). To date, few causative genes have been identified for these diseases.
We recently reviewed genes known to be responsible for EDs in light of their molecular and biological function and proposed a new approach to EDs, integrating both molecular-genetic data and corresponding clinical findings. Based on our previous report, we now propose a clinical-genetic classification of EDs, expand it to other entities in which no causative genes have been identified based on the phenotype, and speculate on possible candidate genes suggested by associated "non-ectodermal" features.


Keywords: ectodermal dysplasia; clinical-functional correlation; epithelial-mesenchymal interaction; ectodermal structural proteins PMID:11546825

Use of mini dental implants in ectodermal dysplasia children: follow-up of three cases.

PubMed

Sfeir, E; Nassif, N; Moukarzel, C

2014-07-01

Ectodermal dysplasia is a hereditary genodermatosis characterised by a congenital defect of ectodermal structures, causing tooth malformations and anomalies. Implantology has become accepted in these subjects. However cases are often complicated by a reduction in the size of the alveolar process, making the insertion of conventional implants difficult without bone grafting. The reduced diameter of mini-implants and their ease of insertion provide an interesting solution in supporting removable or fixed prosthesis. The purpose of this paper is to report the follow-up of three cases of children (11-12 year- old) with ectodermal dysplasia in which mini-implants were used to support the prostheses. In the first case, two mini-implants were inserted into the anterior part of the mandible for stabilising a removable denture (2 years follow-up). In the other two cases, mini- implants were inserted in the maxilla and mandible to replace missing front teeth with fixed prostheses. Patients were called for follow- up every 6 months: in the sencod case follow-up lasted 4 years in the mandible and 2 years in the maxilla; in the third case, 2 years in the maxilla and 1 year in the mandible. The use of mini-implants in children with ectodermal dysplasia can enhance aesthetics, and functional and psychosocial development.

Quantitative Analysis of the Area of the Apical Ectodermal Ridge in Chick Appendages Using Image-J.

PubMed

Syed, Hamd Binte Shahab; Khan, Muhammad Yunus

2018-06-01

To determine the effect of sodium phenytoin on the apical ectodermal ridges (AER) of chick wing buds by using the software program Image-J. An experimental study. Department of Anatomy, Regional Center, College of Physicians and Surgeons Pakistan (CPSP), Islamabad, from January 2014 to January 2015. Sixty fertilised chicken eggs of 'Egyptian fayoumi' breed were selected and separated into experimental (B) and control (A) groups, each having 30 eggs. A single dose of 3.5 mg sodium phenytoin was injected into each egg of the experimental group. The controls were injected with the same volume of normal saline. Developing embryos were extracted 96 hours (day 4) after incubation and histological sections were cut at 5 μm thickness. These sections were stained with Feulgen Nuclear and Light Green. The area of apical ectodermal ridges of chick wing buds was calculated by employing Image-J and subjected to statistical analysis. The difference between the mean values of the area of apical ectodermal ridges of experimental and control groups, as calculated by Image-J, was found to be statistically insignificant. Change in the area of the apical ectodermal ridges in experimental chicks, following phenytoin exposure, was insignificant as proven on the basis of quantification by Image-J.

[Pigmentosum retinis and tubulo-interstitial nephronophtisis in Sensenbrenner syndrome: a case report].

PubMed

Costet, C; Betis, F; Bérard, E; Tsimaratos, M; Sigaudy, S; Antignac, C; Gastaud, P

2000-02-01

Sensenbrenner syndrome or cranio-ectodermal dysplasia is an extremely rare autosomal recessive condition (12 cases reported in literature). Our observation shows the possibility of both ocular and renal involvement associated with cranio-ectodermal abnormalities. and method:We report the case of a girl who presented a typical cranio-ectodermal syndrome with dolicocephaly, short thorax, short limbs, short fingers and teeth abnormalities. At five years, she was found to have pigmentosum retinitis with amblyopy and moderate hyperopia. A chronic renal failure with uncontrollable hypertension underwent a cadaveric-donor transplantation at the age of six years. Two years later, the pigmentosum retinitis was stable. The kidney histology revealed a tubulo-interstitial nephronophtisis. The molecular analysis of the NPH 1 locus, which was associated with nephronophtisis, was negative. Our observation and two recent publications have in common ocular and renal abnormalities associated with cranio-ectodermal dysplasia. The underlying genetic defect would involve not only morphogenesis but also development and maturation of organs as eye and kidney. Sensenbrenner syndrome would thus be similar to certain disorders affecting the eye, kidney, skeleton and ectodermal structures such as the EEM, Senior-Loken, Mainzer-Saldino, and Jeune syndromes. The retinal dystrophy falls within the spectrum of clinical and genetic forms of pigmentosum retinitis. Our observation would confirm possible links between Sensenbrenner syndrome and oculorenal syndromes.

XEDAR activates the non-canonical NF-κB pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verhelst, Kelly, E-mail: Kelly.Verhelst@irc.VIB-UGent.be; Department of Biomedical Molecular Biology, Ghent University, Ghent; Gardam, Sandra, E-mail: s.gardam@garvan.org.au

2015-09-18

Members of the tumor necrosis factor receptor (TNFR) superfamily are involved in a number of physiological and pathological responses by activating a wide variety of intracellular signaling pathways. The X-linked ectodermal dysplasia receptor (XEDAR; also known as EDA2R or TNFRSF27) is a member of the TNFR superfamily that is highly expressed in ectodermal derivatives during embryonic development and binds to ectodysplasin-A2 (EDA-A2), a member of the TNF family that is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Although XEDAR was first described in the year 2000, its function and molecular mechanism of action is still largely unclear. XEDAR hasmore » been reported to activate canonical nuclear factor κB (NF-κB) signaling and mitogen-activated protein (MAP) kinases. Here we report that XEDAR is also able to trigger the non-canonical NF-κB pathway, characterized by the processing of p100 (NF-κB2) into p52, followed by nuclear translocation of p52 and RelB. We provide evidence that XEDAR-induced p100 processing relies on the binding of XEDAR to TRAF3 and TRAF6, and requires the kinase activity of NIK and IKKα. We also show that XEDAR stimulation results in NIK accumulation and that p100 processing is negatively regulated by TRAF3, cIAP1 and A20. - Highlights: • XEDAR activates the non-canonical NF-κB pathway. • XEDAR-induced processing of p100 depends on XEDAR interaction with TRAF3 and TRAF6. • XEDAR-induced processing of p100 depends on NIK and IKKα activity. • Overexpression of XEDAR leads to NIK accumulation. • XEDAR-induced processing of p100 is negatively regulated by TRAF3 cIAP1 and A20.« less

Totipotency, Pluripotency and Nuclear Reprogramming

NASA Astrophysics Data System (ADS)

Mitalipov, Shoukhrat; Wolf, Don

Mammalian development commences with the totipotent zygote which is capable of developing into all the specialized cells that make up the adult animal. As development unfolds, cells of the early embryo proliferate and differentiate into the first two lineages, the pluripotent inner cell mass and the trophectoderm. Pluripotent cells can be isolated, adapted and propagated indefinitely in vitro in an undifferentiated state as embryonic stem cells (ESCs). ESCs retain their ability to differentiate into cells representing the three major germ layers: endoderm, mesoderm or ectoderm or any of the 200+ cell types present in the adult body. Since many human diseases result from defects in a single cell type, pluripotent human ESCs represent an unlimited source of any cell or tissue type for replacement therapy thus providing a possible cure for many devastating conditions. Pluripotent cells resembling ESCs can also be derived experimentally by the nuclear reprogramming of somatic cells. Reprogrammed somatic cells may have an even more important role in cell replacement therapies since the patient's own somatic cells can be used for reprogramming thereby eliminating immune based rejection of transplanted cells. In this review, we summarize two major approaches to reprogramming: (1) somatic cell nuclear transfer and (2) direct reprogramming using genetic manipulations.

Review: the role of neural crest cells in the endocrine system.

PubMed

Adams, Meghan Sara; Bronner-Fraser, Marianne

2009-01-01

The neural crest is a pluripotent population of cells that arises at the junction of the neural tube and the dorsal ectoderm. These highly migratory cells form diverse derivatives including neurons and glia of the sensory, sympathetic, and enteric nervous systems, melanocytes, and the bones, cartilage, and connective tissues of the face. The neural crest has long been associated with the endocrine system, although not always correctly. According to current understanding, neural crest cells give rise to the chromaffin cells of the adrenal medulla, chief cells of the extra-adrenal paraganglia, and thyroid C cells. The endocrine tumors that correspond to these cell types are pheochromocytomas, extra-adrenal paragangliomas, and medullary thyroid carcinomas. Although controversies concerning embryological origin appear to have mostly been resolved, questions persist concerning the pathobiology of each tumor type and its basis in neural crest embryology. Here we present a brief history of the work on neural crest development, both in general and in application to the endocrine system. In particular, we present findings related to the plasticity and pluripotency of neural crest cells as well as a discussion of several different neural crest tumors in the endocrine system.

Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene.

PubMed

Eisenkraft, Arik; Pode-Shakked, Ben; Goldstein, Nurit; Shpirer, Zvi; van Bokhoven, Hans; Anikster, Yair

2015-01-01

Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish descent, in which the index patient presented with a persistent scalp skin lesion, dystrophic nails and light thin hair. Further evaluation revealed over 10 affected individuals in the kindred, over four generations, exhibiting varying degrees of ectodermal involvement. Analysis of the TP63 gene from four of the patients and from two healthy individuals of the same family was performed. Gene sequencing of the patients revealed a nonsense mutation leading to a premature termination codon (PTC) (p.Gln16X). The same mutation was found in all tested affected individuals in the family, but gave rise to marked phenotypic variability with minor clinical manifestations in some individuals, underscoring the clinical heterogeneity associated with the recently described PTC-causing mutations.

Early implant placement for a patient with ectodermal dysplasia: Thirteen years of clinical care.

PubMed

Knobloch, Lisa A; Larsen, Peter E; Saponaro, Paola C; L'Homme-Langlois, Emilie

2017-11-29

Patients with ectodermal dysplasia have abnormalities of 2 or more structures that originate from the ectoderm. The oral manifestations often include the congenital absence of teeth and malformed teeth. This clinical report describes the interdisciplinary care from childhood through the definitive dental rehabilitation completed at skeletal maturation to replace the missing teeth in a patient with ectodermal dysplasia. Treatment began at 9 years of age with an implant-assisted mandibular overdenture to improve function and replace the missing mandibular teeth. Orthodontic treatment for the consolidation of space, composite resin restorations, and interim removable dental prostheses were provided to improve esthetics and replace the missing maxillary teeth. Skeletal growth was monitored, and orthognathic surgery was performed at the cessation of growth. The definitive rehabilitation consisted of a mandibular fixed dental prosthesis supported by dental implants and a maxillary removable dental prosthesis to restore the patient to esthetics and function. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia

PubMed Central

Lim, Young H.; Ovejero, Diana; Sugarman, Jeffrey S.; DeKlotz, Cynthia M.C.; Maruri, Ann; Eichenfield, Lawrence F.; Kelley, Patrick K.; Jüppner, Harald; Gottschalk, Michael; Tifft, Cynthia J.; Gafni, Rachel I.; Boyce, Alison M.; Cowen, Edward W.; Bhattacharyya, Nisan; Guthrie, Lori C.; Gahl, William A.; Golas, Gretchen; Loring, Erin C.; Overton, John D.; Mane, Shrikant M.; Lifton, Richard P.; Levy, Moise L.; Collins, Michael T.; Choate, Keith A.

2014-01-01

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23. PMID:24006476

Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.

PubMed

Lim, Young H; Ovejero, Diana; Sugarman, Jeffrey S; Deklotz, Cynthia M C; Maruri, Ann; Eichenfield, Lawrence F; Kelley, Patrick K; Jüppner, Harald; Gottschalk, Michael; Tifft, Cynthia J; Gafni, Rachel I; Boyce, Alison M; Cowen, Edward W; Bhattacharyya, Nisan; Guthrie, Lori C; Gahl, William A; Golas, Gretchen; Loring, Erin C; Overton, John D; Mane, Shrikant M; Lifton, Richard P; Levy, Moise L; Collins, Michael T; Choate, Keith A

2014-01-15

Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.

Commentary: is totipotency of a human cell a sufficient reason to exclude its patentability under the European law?

PubMed

Vrtovec, Katja Triller; Vrtovec, Bojan

2007-12-01

This article argues that totipotent character of human totipotent cells--defined as the capacity of a cell "to differentiate into all somatic lineages (ectoderm, mesoderm, endoderm), the germ line and extra-embryonic tissues such as the placenta"--is not a sufficient reason to exclude their patentability on the basis of Article 5(1) of the Directive 98/44/EC on the Legal Protection of Biotechnological Inventions (Biopatent Directive), which maintains that "the human body, at the various stages of its formation and development, [...] cannot constitute patentable inventions." Since human totipotent cells have both the potential to generate an entire new organism or to generate only different tissues or organs of an organism, they simultaneously fit the definition of the unpatentable human body at the earliest stage of its formation as well as of an element of the human body, which "may constitute a patentable invention" pursuant to Article 5(2) of the Biopatent Directive, whether that element is isolated from the human body or otherwise produced by means of a technical process. Therefore, this article suggests that, when evaluating patentability of human totipotent cells, they should be further evaluated according to their location and their method of derivation (i.e., whether human totipotent cells are located in the human body, whether they are isolated from the human body, or whether they are produced otherwise by means of a technical process). Disclosure of potential conflicts of interest is found at the end of this article.

Hypohidrotic Ectodermal Dysplasia: Breastfeeding Complications Due to Impaired Breast Development.

PubMed

Wahlbuhl-Becker, Mandy; Faschingbauer, Florian; Beckmann, Matthias W; Schneider, Holm

2017-04-01

Background X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common form of ectodermal dysplasia, is caused by mutations in the gene EDA. While only affected men develop the full-blown clinical picture, females who are heterozygous for an EDA mutation often also show symptoms such as hypodontia, hypotrichosis and hypohidrosis. These women may also suffer from malformations of the mammary gland which represent not just a cosmetic problem but can limit their breastfeeding capability. This paper summarizes the findings of the first systematic study on the impact of hypohidrotic ectodermal dysplasia on breastfeeding. Patients Thirty-eight adult female members of the German-Swiss-Austrian ectodermal dysplasia patient support group participated in a structured interview; most of them also agreed to a photodocumentation of their mammary region. Thirty-one women carried mutations in EDA (Group A) and seven were affected by other forms of hypohidrotic ectodermal dysplasia (Group B). Results 39 % of the women of Group A reported that their breasts were of different size or entirely absent on one side. In Group B, 86 % of the women reported differently sized or even absent breasts; two of these women lacked both breasts entirely. Most women described their nipples as exceptionally flat. 10 % of the women of Group A had more than two nipples. The high percentage of deviations from the norm was confirmed in the photodocumentation. Both groups had few or no sebaceous glands of Montgomery in the areolar region. Around 80 % of interviewed women had children and had attempted to breastfeed their first child. 67 % of the mothers in Group A had had difficulty in breastfeeding their infants and generally attributed this difficulty to their flat nipples. All of the mothers in Group B reported difficulties in breastfeeding; 60 % had not been able to breastfeed their first child. Conclusion Mothers with hypohidrotic ectodermal dysplasia very often have difficulty in breastfeeding because of their impaired breast development. This causal relationship needs to be taken into account in lactation counseling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scarlatescu, Ioana, E-mail: scarlatescuioana@gmail.com; Avram, Calin N.; Virag, Vasile

In this paper we present one treatment plan for irradiation cases which involve a complex technique with multiple beams, using the 3D conformational technique. As the main purpose of radiotherapy is to administrate a precise dose into the tumor volume and protect as much as possible all the healthy tissues around it, for a case diagnosed with a primitive neuro ectoderm tumor, we have developed a new treatment plan, by controlling one of the two adjacent fields used at spinal field, in a way that avoids the fields superposition. Therefore, the risk of overdose is reduced by eliminating the fieldmore » divergence.« less

Atypical Intracranial Epidermoid Cysts: Rare Anomalies with Unique Radiological Features

PubMed Central

Law, Eric K. C.; Lee, Ryan K. L.; Ng, Alex W. H.; Siu, Deyond Y. W.; Ng, Ho-Keung

2015-01-01

Epidermoid cysts are benign slow growing extra-axial tumours that insinuate between brain structures, while their occurrences in intra-axial or intradiploic locations are exceptionally rare. We present the clinical, imaging, and pathological findings in two patients with atypical epidermoid cysts. CT and MRI findings for the first case revealed an intraparenchymal epidermoid cyst that demonstrated no restricted diffusion. The second case demonstrated an aggressive epidermoid cyst that invaded into the intradiploic spaces, transverse sinus, and the calvarium. The timing of ectodermal tissue sequestration during fetal development may account for the occurrence of atypical epidermoid cysts. PMID:25667778

Prosthetic rehabilitation in a pediatric patient with hypohidrotic ectodermal dysplasia: a case report.

PubMed

Quintanilha, Luís Eduardo Lavigne Paranhos; Carneiro-Campos, Luís Eduardo; Antunes, Lívia Azeredo Alves; Antunes, Leonardo Santos; Fernandes, Claudio Pinheiro; Abreu, Fernanda Volpe

2017-01-01

Hypohidrotic ectodermal dysplasia (HED) is a rare ectodermal disease with a systemic expression. Oral abnormalities are common and may include hypodontia and shape irregularities in the primary and permanent dentitions. Rehabilitation of the dental arches in pediatric patients with HED is a challenge because HED is a multifactorial disease that demands a complicated treatment approach and most dentists have limited experience or training in the necessary treatment. In addition, pediatric patients often lack the patience or ability to cooperate with complex prosthetic treatment. This case report describes a simplified technique used to fabricate complete dentures for a 4-year-old HED patient in 4 sessions.

Prosthetic Rehabilitation of a Child Suffering from Hypohidrotic Ectodermal Dysplasia with Complete Anodontia

PubMed Central

Nikhil, M; Chugh, Anshul; Narwal, Anjali

2012-01-01

ABSTRACT A 7-year-old male, described in the case report, exhibited many of the manifestations of ectodermal dysplasia as well as behavioral problems. The treatment to improve his appearance and oral function included a removable prosthesis. The results were significant improvements in speech, masticatory function, and facial esthetics, contributing to the development of normal dietary habits, and the improved and more rapid social integration of the child. How to cite this article: Bala S, Nikhil M, Chugh A, Narwal A. Prosthetic Rehabilitation of a Child Suffering from Hypohidrotic Ectodermal Dysplasia with Complete Anodontia. Int J Clin Pediatr Dent 2012;5(2):148-150. PMID:25206157

Influence of oral rehabilitation on the oral health-related quality of life of a child with ectodermal dysplasia.

PubMed

de Alencar, Nashalie Andrade; Reis, Kátia Rodrigues; Antonio, Andréa Gonçalves; Maia, Lucianne Cople

2015-01-01

Ectodermal dysplasia (ED) is a rare congenital hereditary disorder among a group of syndromes characterized by abnormalities of ectodermic structures. The purpose of this report is to compare the oral health-related quality of life (OHRQoL) before and after complete oral rehabilitation of a five-year-old boy with ED. Delivery of upper and lower dentures resulted in immediate improvement of the child's OHRQoL. Although ED affects patients physically and emotionally, the early oral rehabilitation of young patients is crucial to improve their social interaction and restore their speech and masticatory function.

Ectodermal dysplasia with blindness in sibs on the island of Rodrigues.

PubMed Central

Wallis, C E; Beighton, P

1992-01-01

A brother and sister from the island of Rodrigues had mental retardation, blindness owing to severe ocular malformations, short stature, dysmorphic facial features, hypotrichosis, and dental abnormalities. It is likely that they have a hitherto unrecognised autosomal recessive ectodermal dysplasia syndrome. Images PMID:1583659

Craniofacial morphometric analysis of individuals with X-linked hypohidrotic ectodermal dysplasia.

PubMed

Goodwin, Alice F; Larson, Jacinda R; Jones, Kyle B; Liberton, Denise K; Landan, Maya; Wang, Zhifeng; Boekelheide, Anne; Langham, Margaret; Mushegyan, Vagan; Oberoi, Snehlata; Brao, Rosalie; Wen, Timothy; Johnson, Ramsey; Huttner, Kenneth; Grange, Dorothy K; Spritz, Richard A; Hallgrímsson, Benedikt; Jheon, Andrew H; Klein, Ophir D

2014-09-01

Hypohidrotic ectodermal dysplasia (HED) is the most prevalent type of ectodermal dysplasia (ED). ED is an umbrella term for a group of syndromes characterized by missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. The X-linked recessive (XL), autosomal recessive (AR), and autosomal dominant (AD) types of HED are caused by mutations in the genes encoding ectodysplasin (EDA1), EDA receptor (EDAR), or EDAR-associated death domain (EDARADD). Patients with HED have a distinctive facial appearance, yet a quantitative analysis of the HED craniofacial phenotype using advanced three-dimensional (3D) technologies has not been reported. In this study, we characterized craniofacial morphology in subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED) by use of 3D imaging and geometric morphometrics (GM), a technique that uses defined landmarks to quantify size and shape in complex craniofacial morphologies. We found that the XLHED craniofacial phenotype differed significantly from controls. Patients had a smaller and shorter face with a proportionally longer chin and midface, prominent midfacial hypoplasia, a more protrusive chin and mandible, a narrower and more pointed nose, shorter philtrum, a narrower mouth, and a fuller and more rounded lower lip. Our findings refine the phenotype of XLHED and may be useful both for clinical diagnosis of XLHED and to extend understanding of the role of EDA in craniofacial development.

An evaluation of clinical, radiological and three-dimensional dental tomography findings in ectodermal dysplasia cases.

PubMed

Doğan, Mehmet-Sinan; Callea, Michele; Yavuz, Ìzzet; Aksoy, Orhan; Clarich, Gabriella; Günay, Ayse; Günay, Ahmet; Güven, Sedat; Maglione, Michele; Akkuş, Zeki

2015-05-01

This study aimed to review the results related to head and jaw disorders in cases of ectodermal dysplasia. The evaluation of ectodermal dysplasia cases was made by clinical examination and examination of the jaw and facial areas radiologically and on cone-beam 3-dimensional dental tomography (CBCT) images. In the 36 cases evaluated in the study, typical clinical findings of pure hypohidrotic ectodermal displasia (HED) were seen, such as missing teeth, dry skin, hair and nail disorders. CBCT images were obtained from 12 of the 36 cases, aged 1.5- 45 years, and orthodontic analyses were made on these images. The clinical and radiological evaluations determined, hypodontia or oligodontia, breathing problems, sweating problems, a history of fever, sparse hair, saddle nose, skin peeling, hypopigmentation, hyperpigmentation, finger and nail deformities, conical teeth anomalies, abnormal tooth root formation, tooth resorption in the root, gingivitis, history of epilepsy, absent lachrymal canals and vision problems in the cases which included to the study. Ectodermal dysplasia cases have a particular place in dentistry and require a professional, multi-disciplinary approach in respect of the chewing function, orthognathic problems, growth, oral and dental health. It has been understood that with data obtained from modern technologies such as three-dimensional dental tomography and the treatments applied, the quality of life of these cases can be improved.

Characterization of X-linked Hypohidrotic Ectodermal Dysplasia (XL-HED) Hair and Sweat Gland Phenotypes Using Phototrichogram Analysis and Live Confocal Imaging

PubMed Central

Jones, Kyle B.; Goodwin, Alice F.; Landan, Maya; Seidel, Kerstin; Tran, Dong-Kha; Hogue, Jacob; Chavez, Miquella; Fete, Mary; Yu, Wenli; Hussein, Tarek; Johnson, Ramsey; Huttner, Kenneth; Jheon, Andrew H.; Klein, Ophir D.

2015-01-01

Hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia (ED), which encompasses a large group of syndromes that share several phenotypic features such as missing or malformed ectodermal structures, including skin, hair, sweat glands, and teeth. X-linked hypohidrotic ectodermal dysplasia (XL-HED) is associated with mutations in ectodysplasin (EDA1). Hypohidrosis due to hypoplastic sweat glands and thin, sparse hair are phenotypic features that significantly affect the daily lives of XL-HED individuals and therefore require systematic analysis. We sought to determine the quality of life of individuals with XL-HED and to quantify sweat duct and hair phenotypes using confocal imaging, pilocarpine iontophoresis, and phototrichogram analysis. Using these highly sensitive and non-invasive techniques, we demonstrated that 11/12 XL-HED individuals presented with a complete absence of sweat ducts and that none produced sweat. We determined that the thin hair phenotype observed in XL-HED was due to multiple factors, such as fewer terminal hairs with decreased thickness and slower growth rate, as well as fewer follicular units and fewer hairs per unit. The precise characterization of XL-HED phenotypes using sensitive and non-invasive techniques presented in our study will improve upon larger genotype-phenotype studies and in the assessment of future therapies in XL-HED. PMID:23687000

Commitment of chondrogenic precursors of the avian scapula takes place after epithelial-mesenchymal transition of the dermomyotome

PubMed Central

2010-01-01

Background Cells of the epithelially organised dermomyotome are traditionally believed to give rise to skeletal muscle and dermis. We have previously shown that the dermomyotome can undergo epithelial-mesenchymal transition (EMT) and give rise to chondrogenic cells, which go on to form the scapula blade in birds. At present we have little understanding regarding the issue of when the chondrogenic fate of dermomyotomal cells is determined. Using quail-chick grafting experiments, we investigated whether scapula precursor cells are committed to a chondrogenic fate while in an epithelial state or whether commitment is established after EMT. Results We show that the hypaxial dermomyotome, which normally forms the scapula, does not generate cartilaginous tissue after it is grafted to the epaxial domain. In contrast engraftment of the epaxial dermomyotome to the hypaxial domain gives rise to scapula-like cartilage. However, the hypaxial sub-ectodermal mesenchyme (SEM), which originates from the hypaxial dermomyotome after EMT, generates cartilaginous elements in the epaxial domain, whereas in reciprocal grafting experiments, the epaxial SEM cannot form cartilage in the hypaxial domain. Conclusions We suggest that the epithelial cells of the dermomyotome are not committed to the chondrogenic lineage. Commitment to this lineage occurs after it has undergone EMT to form the sub-ectodermal mesenchyme. PMID:20807426

Distinct embryotoxic effects of lithium appeared in a new assessment model of the sea urchin: the whole embryo assay and the blastomere culture assay.

PubMed

Kiyomoto, Masato; Morinaga, Seiko; Ooi, Nagisa

2010-03-01

Early embryogenesis is one of the most sensitive and critical stages in animal development. Here we propose a new assessment model on the effect of pollutant to multicellular organism development. That is a comparison between the whole embryo assay and the blastomere culture assay. We examined the LiCl effect on the sea urchin early development in both of whole embryos and the culture of isolated blastomeres. The mesoderm and endoderm region were capable to differentiate into skeletogenic cells when they were isolated at 60-cell stage and cultured in vitro. The embryo developed to exogastrula by the vegetalizing effect of the same LiCl condition where ectodermal region changed their fate to endoderm, while the isolated blastomeres from the presumptive ectoderm region differentiated into skeletogenic cells in the culture with LiCl. The effect of LiCl to the sea urchin embryo and to the dissociated blastomere is a unique example where same cells response distinctly to the same agent depend on the condition around them. Present results show the importance of examining the process in cellular and tissue levels for the exact understanding on the morphological effect of chemicals and metals.

Planar induction of anteroposterior pattern in the developing central nervous system of Xenopus laevis

NASA Technical Reports Server (NTRS)

Doniach, T.; Phillips, C. R.; Gerhart, J. C.

1992-01-01

It has long been thought that anteroposterior (A-P) pattern in the vertebrate central nervous system is induced in the embryo's dorsal ectoderm exclusively by signals passing vertically from underlying, patterned dorsal mesoderm. Explants from early gastrulae of the frog Xenopus laevis were prepared in which vertical contact between dorsal ectoderm and mesoderm was prevented but planar contact was maintained. In these, four position-specific neural markers (engrailed-2, Krox-20, XlHbox 1, and XlHbox 6) were expressed in the ectoderm in the same A-P order as in the embryo. Thus, planar signals alone, following a path available in the normal embryo, can induce A-P neural pattern.

Uncoupling neurogenic gene networks in the Drosophila embryo.

PubMed

Rogers, William A; Goyal, Yogesh; Yamaya, Kei; Shvartsman, Stanislav Y; Levine, Michael S

2017-04-01

The EGF signaling pathway specifies neuronal identities in the Drosophila embryo by regulating developmental patterning genes such as intermediate neuroblasts defective ( ind ). EGFR is activated in the ventral midline and neurogenic ectoderm by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline, was found to be the dominant source of EGF patterning activity. We suggest that Drosophila is undergoing an evolutionary transition in central nervous system (CNS)-organizing activity from the ventral midline to the neurogenic ectoderm. © 2017 Rogers et al.; Published by Cold Spring Harbor Laboratory Press.

Derivation, propagation and differentiation of human embryonic stem cells.

PubMed

Conley, Brock J; Young, Julia C; Trounson, Alan O; Mollard, Richard

2004-04-01

Embryonic stem (ES) cells are in vitro cultivated pluripotent cells derived from the inner cell mass (ICM) of the embryonic blastocyst. Attesting to their pluripotency, ES cells can be differentiated into representative derivatives of all three embryonic germ layers (endoderm, ectoderm and mesoderm) both in vitro and in vivo. Although mouse ES cells have been studied for many years, human ES cells have only more recently been derived and successfully propagated. Many biochemical differences and culture requirements between mouse and human ES cells have been described, yet despite these differences the study of murine ES cells has provided important insights into methodologies aimed at generating a greater and more in depth understanding of human ES cell biology. One common feature of both mouse and human ES cells is their capacity to undergo controlled differentiation into spheroid structures termed embryoid bodies (EBs). EBs recapitulate several aspects of early development, displaying regional-specific differentiation programs into derivatives of all three embryonic germ layers. For this reason, EB formation has been utilised as an initial step in a wide range of studies aimed at differentiating both mouse and human ES cells into a specific and desired cell type. Recent reports utilising specific growth factor combinations and cell-cell induction systems have provided alternative strategies for the directed differentiation of cells into a desired lineage. According to each one of these strategies, however, a relatively high cell lineage heterogeneity remains, necessitating subsequent purification steps including mechanical dissection, selective media or fluorescent or magnetic activated cell sorting (FACS and MACS, respectively). In the future, the ability to specifically direct differentiation of human ES cells at 100% efficiency into a desired lineage will allow us to fully explore the potential of these cells in the analysis of early human development, drug discovery, drug testing and repair of damaged or diseased tissues via transplantation.

Expression and phylogenetic analysis of the zic gene family in the evolution and development of metazoans

PubMed Central

2010-01-01

Background zic genes are members of the gli/glis/nkl/zic super-family of C2H2 zinc finger (ZF) transcription factors. Homologs of the zic family have been implicated in patterning neural and mesodermal tissues in bilaterians. Prior to this study, the origin of the metazoan zic gene family was unknown and expression of zic gene homologs during the development of early branching metazoans had not been investigated. Results Phylogenetic analyses of novel zic candidate genes identified a definitive zic homolog in the placozoan Trichoplax adhaerens, two gli/glis/nkl-like genes in the ctenophore Mnemiopsis leidyi, confirmed the presence of three gli/glis/nkl-like genes in Porifera, and confirmed the five previously identified zic genes in the cnidarian Nematostella vectensis. In the cnidarian N. vectensis, zic homologs are expressed in ectoderm and the gastrodermis (a bifunctional endomesoderm), in presumptive and developing tentacles, and in oral and sensory apical tuft ectoderm. The Capitella teleta zic homolog (Ct-zic) is detectable in a subset of the developing nervous system, the foregut, and the mesoderm associated with the segmentally repeated chaetae. Lastly, expression of gli and glis homologs in Mnemiopsis. leidyi is detected exclusively in neural cells in floor of the apical organ. Conclusions Based on our analyses, we propose that the zic gene family arose in the common ancestor of the Placozoa, Cnidaria and Bilateria from a gli/glis/nkl-like gene and that both ZOC and ZF-NC domains evolved prior to cnidarian-bilaterian divergence. We also conclude that zic expression in neural ectoderm and developing neurons is pervasive throughout the Metazoa and likely evolved from neural expression of an ancestral gli/glis/nkl/zic gene. zic expression in bilaterian mesoderm may be related to the expression in the gastrodermis of a cnidarian-bilaterian common ancestor. PMID:21054859

Embryological Development: Evolutionary History, Genetic Bias, and Cellular Environment Control the Flow of Developmental Events, Part II.

ERIC Educational Resources Information Center

Caplan, Arnold I.

1981-01-01

Emphasizes ectodermal-mesodermal interaction but focuses on the genesis of specialized structures like feathers (ectodermal) and muscles, cartilage, and bone. The sum of these interactions and other factors which govern normal development may be important in regulating the regeneration of particular structures in postembryonic individuals.…

Prosthodontic rehabilitation in patient with ectodermal dysplasia combining preprosthetic techniques: a case report.

PubMed

Pombo Castro, María; Luaces Rey, Ramón; Arenaz Búa, Jorge; Santana-Mora, Urbano; López-Cedrún Cembranos, José Luís

2013-10-01

Oral manifestations in ectodermal dysplasia include oligodontia, alveolar ridges hypoplasia, and others. Due to the special conditions in terms of unhealthy teeth and lack of bone, implant-supported rehabilitation seems to offer the most satisfactory outcome. A 27-year-old male diagnosed with ectodermal dysplasia was referred to our department for oral rehabilitation. Oral manifestations included oligodontia, maxillary and mandibular atrophy, mandibular alveolar ridge with knife-edge morphology, and conical teeth. Treatment planning consisted of a Le Fort I osteotomy with interpositional grafts, bilateral sinus lift, and placement of maxillary and mandibular inlay and onlay corticocancellous grafts, using autologous iliac crest bone. In the second surgery, all remaining teeth were removed and 11 endosteal implants were placed. Six months after implant placement, a bimaxillary fixed implant-supported prosthesis was delivered, maintaining a satisfactory esthetic and functional result after a 2-year follow-up. The use of combined preprosthetic techniques allows the placement of endosteal implants and a fixed implant-supported prosthesis in patients with oligodontia and ectodermal dysplasia, providing an esthetic and functional oral rehabilitation.

Dentomaxillofacial characteristics of ectodermal dysplasia.

PubMed

Nakayama, Yumiko; Baba, Yoshiyuki; Tsuji, Michiko; Fukuoka, Hiroki; Ogawa, Takuya; Ohkuma, Mizue; Moriyama, Keiji

2015-02-01

The aim of this retrospective hospital-based study was to elucidate the dentomaxillofacial characteristics of ectodermal dysplasia. Six Japanese individuals (one male and five female; age range, 12.7-27.2 years) underwent comprehensive examinations, including history recording, cephalometric analysis, panoramic radiography, and analysis of dental models. All the subjects had two or more major manifestations for clinical diagnosis of ectodermal dysplasia (e.g., defects of hair, teeth, nails, and sweat glands). They presented hypodontia (mean number of missing teeth, 9.5; range, 5-14), especially in the premolar region, and enamel dysplasia. Five subjects had bilateral molar occlusion, whereas one subject had unilateral molar occlusion. The common skeletal features were small facial height, maxillary hypoplasia, counterclockwise rotation of the mandible, and mandibular protrusion. Interestingly, the maxillary first molars were located in higher positions and the upper anterior facial height was smaller than the Japanese norm. The results suggest that vertical and anteroposterior maxillary growth retardation, rather than lack of occlusal support due to hypodontia, leads to reduced anterior facial height in individuals with ectodermal dysplasia. © 2014 Japanese Teratology Society.

Tissue-Associated “Candidatus Mycoplasma corallicola” and Filamentous Bacteria on the Cold-Water Coral Lophelia pertusa (Scleractinia)▿ †

PubMed Central

Neulinger, Sven C.; Gärtner, Andrea; Järnegren, Johanna; Ludvigsen, Martin; Lochte, Karin; Dullo, Wolf-Christian

2009-01-01

The cold-water coral Lophelia pertusa (Scleractinia, Caryophylliidae) is a key species in the formation of cold-water reefs, which are among the most diverse deep-sea ecosystems. It occurs in two color varieties: white and red. Bacterial communities associated with Lophelia have been investigated in recent years, but the role of the associated bacteria remains largely obscure. This study uses catalyzed reporter deposition fluorescence in situ hybridization to detect the in situ location of specific bacterial groups on coral specimens from the Trondheimsfjord (Norway). Two tissue-associated groups were identified: (i) bacteria on the host's tentacle ectoderm, “Candidatus Mycoplasma corallicola,” are flasklike, pointed cells and (ii) endoderm-associated bona fide TM7 bacteria form long filaments in the gastral cavity. These tissue-bound bacteria were found in all coral specimens from the Trondheimsfjord, indicating a closer relationship with the coral compared to bacterial assemblages present in coral mucus and gastric fluid. PMID:19114511

Characterizing the mechanical behavior of the zebrafish germ layers

NASA Astrophysics Data System (ADS)

Kealhofer, David; Serwane, Friedhelm; Mongera, Alessandro; Rowghanian, Payam; Lucio, Adam; Campàs, Otger

Organ morphogenesis and the development of the animal body plan involve complex spatial and temporal control of tissue- and cell-level mechanics. A prime example is the generation of stresses by individual cells to reorganize the tissue. These processes have remained poorly understood due to a lack of techniques to characterize the local constitutive law of the material, which relates local cellular forces to the resulting tissue flows. We have developed a method for quantitative, local in vivo study of material properties in living tissue using magnetic droplet probes. We use this technique to study the material properties of the different zebrafish germ layers using aggregates of zebrafish mesendodermal and ectodermal cells as a model system. These aggregates are ideal for controlled studies of the mechanics of individual germ layers because of the homogeneity of the cell type and the simple spherical geometry. Furthermore, the numerous molecular tools and transgenic lines already developed for this model organism can be applied to these aggregates, allowing us to characterize the contributions of cell cortex tension and cell adhesion to the mechanical properties of the zebrafish germ layers.

Two-Tiered Control of Epithelial Growth and Autophagy by the Insulin Receptor and the Ret-Like Receptor, Stitcher

PubMed Central

O'Farrell, Fergal; Wang, Shenqiu; Katheder, Nadja

2013-01-01

Body size in Drosophila larvae, like in other animals, is controlled by nutrition. Nutrient restriction leads to catabolic responses in the majority of tissues, but the Drosophila mitotic imaginal discs continue growing. The nature of these differential control mechanisms that spare distinct tissues from starvation are poorly understood. Here, we reveal that the Ret-like receptor tyrosine kinase (RTK), Stitcher (Stit), is required for cell growth and proliferation through the PI3K-I/TORC1 pathway in the Drosophila wing disc. Both Stit and insulin receptor (InR) signaling activate PI3K-I and drive cellular proliferation and tissue growth. However, whereas optimal growth requires signaling from both InR and Stit, catabolic changes manifested by autophagy only occur when both signaling pathways are compromised. The combined activities of Stit and InR in ectodermal epithelial tissues provide an RTK-mediated, two-tiered reaction threshold to varying nutritional conditions that promote epithelial organ growth even at low levels of InR signaling. PMID:23935447

Making maxillary barbels with a proximal-distal gradient of Wnt signals in matrix-bound mesenchymal cells

PubMed Central

Figueroa, Francisco; Singer, Susan S.; LeClair, Elizabeth E.

2015-01-01

The evolution of specific appendages is made possible by the ontogenetic deployment of general cell signaling pathways. Many fishes, amphibians and reptiles have unique skin appendages known as barbels, which are poorly understood at the cellular and molecular level. In this study, we examine the cell arrangements, cell division patterns, and gene expression profiles associated with the zebrafish maxillary barbel, or ZMB. The earliest cellular organization of the ZMB is an internal whorl of mesenchymal cells in the dermis of the maxilla; there is no epithelial placode, nor any axially-elongated epithelial cells as expected of an apical ectodermal ridge (AER). As the ZMB develops, cells in S-phase are at first distributed randomly throughout the appendage, gradually transitioning to a proliferative population concentrated at the distal end. By observing ZMB ontogenetic stages in a Wnt-responsive transgenic reporter line, TCFsiam, we identified a strongly fluorescent mesenchymal cell layer within these developing appendages. Using an in vitro explant culture technique on developing barbel tissues, we co-localized the fluorescent label in these cells with the mitotic marker EdU. Surprisingly, TCF+ cells showed little proliferation, indicating a slow-cycling subpopulation. Transmission electron microscopy of the ZMB located the TCF+ cells in a single, circumferential layer within the barbel’s matrix core. Morphologically, these cells resemble fibroblasts or osteoblasts; in addition to their matrix-bound location, they are identified by their pancake-shaped nuclei, abundant rough endoplasmic reticulum, and cytoplasmic extensions into the surrounding extracellular matrix. Taken together, these features define a novel mesenchymal cell population in zebrafish, the ‘TCF+ core cells.’ A working model of barbel development is proposed, in which these minimally mitotic mesodermal cells produce collagenous matrix in response to ectodermally-derived Wnt signals deployed in a proximal-distal gradient along the appendage. This documents a novel mechanism of vertebrate appendage outgrowth. Similar genetic signals and cell behaviors may be responsible for the independent and repeated evolution of barbel structures in other fish species. PMID:26492827

A Splice Defect in the EDA Gene in Dogs with an X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Phenotype.

PubMed

Waluk, Dominik P; Zur, Gila; Kaufmann, Ronnie; Welle, Monika M; Jagannathan, Vidhya; Drögemüller, Cord; Müller, Eliane J; Leeb, Tosso; Galichet, Arnaud

2016-09-08

X-linked hypohidrotic ectodermal dysplasia (XLHED) caused by variants in the EDA gene represents the most common ectodermal dysplasia in humans. We investigated three male mixed-breed dogs with an ectodermal dysplasia phenotype characterized by marked hypotrichosis and multifocal complete alopecia, almost complete absence of sweat and sebaceous glands, and altered dentition with missing and abnormally shaped teeth. Analysis of SNP chip genotypes and whole genome sequence data from the three affected dogs revealed that the affected dogs shared the same haplotype on a large segment of the X-chromosome, including the EDA gene. Unexpectedly, the whole genome sequence data did not reveal any nonsynonymous EDA variant in the affected dogs. We therefore performed an RNA-seq experiment on skin biopsies to search for changes in the transcriptome. This analysis revealed that the EDA transcript in the affected dogs lacked 103 nucleotides encoded by exon 2. We speculate that this exon skipping is caused by a genetic variant located in one of the large introns flanking this exon, which was missed by whole genome sequencing with the illumina short read technology. The altered EDA transcript splicing most likely causes the observed ectodermal dysplasia in the affected dogs. These dogs thus offer an excellent opportunity to gain insights into the complex splicing processes required for expression of the EDA gene, and other genes with large introns. Copyright © 2016 Waluk et al.

Genotype-phenotype correlation in boys with X-linked hypohidrotic ectodermal dysplasia.

PubMed

Burger, Kristin; Schneider, Anne-Theres; Wohlfart, Sigrun; Kiesewetter, Franklin; Huttner, Kenneth; Johnson, Ramsey; Schneider, Holm

2014-10-01

X-linked hypohidrotic ectodermal dysplasia (XLHED), the most frequent form of ectodermal dysplasia, is a genetic disorder of ectoderm development characterized by malformation of multiple ectodermal structures such as skin, hair, sweat and sebaceous glands, and teeth. The disease is caused by a broad spectrum of mutations in the gene EDA. Although XLHED symptoms show inter-familial and intra-familial variability, genotype-phenotype correlation has been demonstrated with respect to sweat gland function. In this study, we investigated to which extent the EDA genotype correlates with the severity of XLHED-related skin and hair signs. Nineteen male children with XLHED (age range 3-14 years) and seven controls (aged 6-14 years) were examined by confocal microscopy of the skin, quantification of pilocarpine-induced sweating, semi-quantitative evaluation of full facial photographs with respect to XLHED-related skin issues, and phototrichogram analysis. All eight boys with known hypomorphic EDA mutations were able to produce at least some sweat and showed less severe cutaneous signs of XLHED than the anhidrotic XLHED patients (e.g., perioral and periorbital eczema or hyperpigmentation, regional hyperkeratosis, characteristic wrinkles under the eyes). As expected, individuals with XLHED had significantly less and thinner hair than healthy controls. However, there were also significant differences in hair number, diameter, and other hair characteristics between the group with hypomorphic EDA mutations and the anhidrotic patients. In summary, this study indicated a remarkable genotype-phenotype correlation of skin and hair findings in prepubescent males with XLHED. © 2014 Wiley Periodicals, Inc.

Natural and Artificial Intelligence, Language, Consciousness, Emotion, and Anticipation

NASA Astrophysics Data System (ADS)

Dubois, Daniel M.

2010-11-01

The classical paradigm of the neural brain as the seat of human natural intelligence is too restrictive. This paper defends the idea that the neural ectoderm is the actual brain, based on the development of the human embryo. Indeed, the neural ectoderm includes the neural crest, given by pigment cells in the skin and ganglia of the autonomic nervous system, and the neural tube, given by the brain, the spinal cord, and motor neurons. So the brain is completely integrated in the ectoderm, and cannot work alone. The paper presents fundamental properties of the brain as follows. Firstly, Paul D. MacLean proposed the triune human brain, which consists to three brains in one, following the species evolution, given by the reptilian complex, the limbic system, and the neo-cortex. Secondly, the consciousness and conscious awareness are analysed. Thirdly, the anticipatory unconscious free will and conscious free veto are described in agreement with the experiments of Benjamin Libet. Fourthly, the main section explains the development of the human embryo and shows that the neural ectoderm is the whole neural brain. Fifthly, a conjecture is proposed that the neural brain is completely programmed with scripts written in biological low-level and high-level languages, in a manner similar to the programmed cells by the genetic code. Finally, it is concluded that the proposition of the neural ectoderm as the whole neural brain is a breakthrough in the understanding of the natural intelligence, and also in the future design of robots with artificial intelligence.

PubMed Central

Wahlbuhl-Becker, Mandy; Faschingbauer, Florian; Beckmann, Matthias W.; Schneider, Holm

2017-01-01

Background X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common form of ectodermal dysplasia, is caused by mutations in the gene EDA. While only affected men develop the full-blown clinical picture, females who are heterozygous for an EDA mutation often also show symptoms such as hypodontia, hypotrichosis and hypohidrosis. These women may also suffer from malformations of the mammary gland which represent not just a cosmetic problem but can limit their breastfeeding capability. This paper summarizes the findings of the first systematic study on the impact of hypohidrotic ectodermal dysplasia on breastfeeding. Patients Thirty-eight adult female members of the German-Swiss-Austrian ectodermal dysplasia patient support group participated in a structured interview; most of them also agreed to a photodocumentation of their mammary region. Thirty-one women carried mutations in EDA (Group A) and seven were affected by other forms of hypohidrotic ectodermal dysplasia (Group B). Results 39 % of the women of Group A reported that their breasts were of different size or entirely absent on one side. In Group B, 86 % of the women reported differently sized or even absent breasts; two of these women lacked both breasts entirely. Most women described their nipples as exceptionally flat. 10 % of the women of Group A had more than two nipples. The high percentage of deviations from the norm was confirmed in the photodocumentation. Both groups had few or no sebaceous glands of Montgomery in the areolar region. Around 80 % of interviewed women had children and had attempted to breastfeed their first child. 67 % of the mothers in Group A had had difficulty in breastfeeding their infants and generally attributed this difficulty to their flat nipples. All of the mothers in Group B reported difficulties in breastfeeding; 60 % had not been able to breastfeed their first child. Conclusion Mothers with hypohidrotic ectodermal dysplasia very often have difficulty in breastfeeding because of their impaired breast development. This causal relationship needs to be taken into account in lactation counseling. PMID:28553001

Regional differences in BMP-dependence of dorsoventral patterning in the leech Helobdella.

PubMed

Kuo, Dian-Han; Shankland, Marty; Weisblat, David A

2012-08-01

In the leech Helobdella, the ectoderm exhibits a high degree of morphological homonomy between body segments, but pattern elements in lateral ectoderm arise via distinct cell lineages in the segments of the rostral and midbody regions. In each of the four rostral segments, a complete set of ventrolateral (O fate) and dorsolateral (P fate) ectodermal pattern elements arises from a single founder cell, op. In the 28 midbody and caudal segments, however, there are two initially indeterminate o/p founder cells; the more dorsal of these is induced to adopt the P fate by BMP5-8 emanating from the dorsalmost ectoderm, while the more ventral cell assumes the O fate. Previous work has suggested that the dorsoventral patterning of O and P fates differs in the rostral region, but the role of BMP signaling in those segments has not been investigated. We show here that suppression of dorsal BMP5-8 signaling (which effects a P-to-O fate change in the midbody) has no effect on the patterning of O and P fates in the rostral region. Furthermore, ectopic expression of BMP5-8 in the ventral ectoderm (which induces an O-to-P fate change in the midbody) has no effect in the rostral region. Finally, expression of a dominant-negative BMP receptor (which induces a P-to-O fate change in the midbody) fails to affect O/P patterning in the rostral region. Thus, the rostral segments appear to use some mechanism other than BMP signaling to pattern O and P cell fates along the dorsoventral axis. From a mechanistic standpoint, the OP lineage of the rostral segments and the O-P equivalence group of the midbody and caudal segments constitute distinct developmental modules that rely to differing degrees on positional cues from surrounding ectoderm in order to specify homonomous cell fates. Copyright © 2012 Elsevier Inc. All rights reserved.

Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method.

PubMed

Ohnishi, Hiroe; Skerleva, Desislava; Kitajiri, Shin-ichiro; Sakamoto, Tatsunori; Yamamoto, Norio; Ito, Juichi; Nakagawa, Takayuki

2015-07-10

Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Growth, nutritional, and gastrointestinal aspects of ankyloblepharon-ectodermal defect-cleft lip and/or palate (AEC) syndrome

USDA-ARS?s Scientific Manuscript database

Ankyloblepharon-ectodermal defect-cleft lip and/or palate (AEC), is a rare genetic disorder due to mutations in the TP63 gene. In the present study, we characterized the pattern of growth and body composition, and the nutritional and gastrointestinal aspects of children and adults (n = 18) affected ...

Ocular and non-ocular manifestations of hypohidrotic ectodermal dysplasia

PubMed Central

Tyagi, Pallavi; Tyagi, Vipin; Hashim, Adnan A

2011-01-01

Hypohidrotic ectodermal dysplasia (HED) is a group of rare multisystemic genetic syndromes that affects ectodermal structures such as skin, hair, nails, teeth and sweat glands. The authors present a case of a child with ocular and dermatological signs of HED along with severe involvement of other multiple organ systems. The family history could be traced to four generations and there was an observed trend of increase in severity of signs and symptoms occurring at younger age. The purpose of this case report is to create awareness in ophthalmic community of its diagnosis and clinical manifestations. This case highlights the role of multidisciplinary approach for management of systemic disease, genetic evaluation of affected individuals and carriers and genetic counselling. PMID:22700604

Major regulatory factors in the evolution of development: the roles of goosecoid and Msx in the evolution of the direct-developing sea urchin Heliocidaris erythrogramma.

PubMed

Wilson, Keen A; Andrews, Mary E; Rudolf Turner, F; Raff, Rudolf A

2005-01-01

The transcription factors Gsc and Msx are expressed in the oral ectoderm of the indirect-developing sea urchin Heliocidaris tuberculata. Their patterns of expression are highly modified in the direct developer Heliocidaris erythrogramma, which lacks an oral ectoderm. We here test the hypothesis that they are large effect genes responsible for the loss of the oral ectoderm module in the direct-developing larva of H. erythrogramma as well as for the restoration of an overt oral ectoderm in H.e. xH.t. hybrids. We undertook misexpression/overexpression and knockdown assays in the two species and in hybrids by mRNA injection. The results indicate that dramatic changes of function of these transcription factors has occurred. One of these genes, Gsc, has the ability when misexpressed to partially restore oral ectoderm in H. erythrogramma. On the other hand, Msx has lost any oral function and instead has a role in mesoderm proliferation and patterning. In addition, we found that the H. tuberculataGsc is up regulated in H.e. xH.t. hybrids, showing a preferential use of the indirect developing parental gene in the development of the hybrid. We suggest that Gsc qualifies as a gene of large evolutionary effect and is partially responsible for the evolution of direct development of H. erythrogramma. We discuss these results in light of modularity and genetic networks in development, as well as in their implications for the rapid evolution of large morphological changes in development.

bicaudal-C is required for the formation of anterior neurogenic ectoderm in the sea urchin embryo.

PubMed

Yaguchi, Shunsuke; Yaguchi, Junko; Inaba, Kazuo

2014-10-31

bicaudal-C (bicC) mRNA encodes a protein containing RNA-binding domains that is reported to be maternally present with deflection in the oocytes/eggs of some species. The translated protein plays a critical role in the regulation of cell fate specification along the body axis during early embryogenesis in flies and frogs. However, it is unclear how it functions in eggs in which bicC mRNA is uniformly distributed, for instance, sea urchin eggs. Here, we show the function of BicC in the formation of neurogenic ectoderm of the sea urchin embryo. Loss-of-function experiments reveal that BicC is required for serotonergic neurogenesis and for expression of ankAT-1 gene, which is essential for the formation of apical tuft cilia in the neurogenic ectoderm of the sea urchin embryo. In contrast, the expression of FoxQ2, the neurogenic ectoderm specification transcription factor, is invariant in BicC morphants. Because FoxQ2 is an upstream factor of serotonergic neurogenesis and ankAT-1 expression, these data indicate that BicC functions in regulating the events that are coordinated by FoxQ2 during sea urchin embryogenesis.

Noninvasive Prenatal Diagnosis of Hypohidrotic Ectodermal Dysplasia by Tooth Germ Sonography.

PubMed

Wünsche, S; Jüngert, J; Faschingbauer, F; Mommsen, H; Goecke, T; Schwanitz, K; Stepan, H; Schneider, H

2015-08-01

Hypohidrotic ectodermal dysplasia, a potentially life-threatening heritable disorder, may be recognized already in utero by characteristic features such as oligodontia and mandibular hypoplasia. As therapeutic options and prognosis depend on the time point of diagnosis, early recognition was attempted during routine prenatal ultrasound examinations. Fetuses of nine pregnant women (one triplet and eight singleton pregnancies) with family histories of hypohidrotic ectodermal dysplasia were investigated by sonography between the 20th and 24th week of gestation. In 4 male and 2 female fetuses reduced amounts of tooth germs were detected, whereas 5 fetal subjects showed the normal amount. Three-dimensional ultrasound evaluation revealed mandibular hypoplasia in 5 of the 6 fetuses with oligodontia. Molecular genetic analysis and/or clinical findings after birth confirmed the prenatal sonographic diagnosis in each subject. In subjects with a family history of hypohidrotic ectodermal dysplasia, the diagnosis of this rare condition can be established noninvasively by sonography in the second trimester of pregnancy. Early recognition of the disorder may help to prevent dangerous hyperthermic episodes in infancy and may allow timely therapeutic interventions. © Georg Thieme Verlag KG Stuttgart · New York.

Specification of epibranchial placodes in zebrafish.

PubMed

Nechiporuk, Alexei; Linbo, Tor; Poss, Kenneth D; Raible, David W

2007-02-01

In all vertebrates, the neurogenic placodes are transient ectodermal thickenings that give rise to sensory neurons of the cranial ganglia. Epibranchial (EB) placodes generate neurons of the distal facial, glossopharyngeal and vagal ganglia, which convey sensation from the viscera, including pharyngeal endoderm structures, to the CNS. Recent studies have implicated signals from pharyngeal endoderm in the initiation of neurogenesis from EB placodes; however, the signals underlying the formation of placodes are unknown. Here, we show that zebrafish embryos mutant for fgf3 and fgf8 do not express early EB placode markers, including foxi1 and pax2a. Mosaic analysis demonstrates that placodal cells must directly receive Fgf signals during a specific crucial period of development. Transplantation experiments and mutant analysis reveal that cephalic mesoderm is the source of Fgf signals. Finally, both Fgf3 and Fgf8 are sufficient to induce foxi1-positive placodal precursors in wild-type as well as Fgf3-plus Fgf8-depleted embryos. We propose a model in which mesoderm-derived Fgf3 and Fgf8 signals establish both the EB placodes and the development of the pharyngeal endoderm, the subsequent interaction of which promotes neurogenesis. The coordinated interplay between craniofacial tissues would thus assure proper spatial and temporal interactions in the shaping of the vertebrate head.

Genitourinary malformations: an under-recognized feature of ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome.

PubMed

Hyder, Zerin; Beale, Victoria; O'Connor, Ruth; Clayton-Smith, Jill

2017-04-01

The ectodermal dysplasia and cleft lip/palate (EEC) syndrome describes the association of ectrodactyly, ectodermal dysplasia and orofacial clefting. As with many autosomal dominant disorders, there is variability in expression and not all of these three core features are present in every individual with the condition. Moreover, there may be additional associated features, which are under-recognized. One of these is the presence of genitourinary anomalies, some of which cause significant morbidity. This report details a further two patients with EEC syndrome and genitourinary involvement, including flaccid megacystis with detrusor muscle failure, bilateral hydronephrosis and megaureter, requiring significant renal and urological involvement during their childhood. We go on to review the literature on the diagnosis and management of genitourinary malformations in EEC syndrome.

A novel mutation in the EDAR gene causes severe autosomal recessive hypohidrotic ectodermal dysplasia.

PubMed

Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, Dorte Launholt; Jensen, Peter Kjestrup Axel

2014-08-01

We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient. © 2014 Wiley Periodicals, Inc.

Acquisition of the dorsal structures in chordate amphioxus.

PubMed

Morov, Arseniy R; Ukizintambara, Tharcisse; Sabirov, Rushan M; Yasui, Kinya

2016-06-01

Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore. The lefty domain co-expresses zygotic nodal by the initial gastrula stage on the one side of the blastopore margin and induces the expression of goosecoid, not-like, chordin and brachyury1 genes in this region, as in the oral ectoderm of sea urchin embryos, which provides a basis for the formation of the dorsal structures. The striking similarity in the gene regulations and their respective expression domains when comparing dorsal formation in amphioxus and the determination of the oral ectoderm in sea urchin embryos suggests that chordates derived from an ambulacrarian-type blastula with dorsoventral inversion. © 2016 The Authors.

Acquisition of the dorsal structures in chordate amphioxus

PubMed Central

Morov, Arseniy R.; Ukizintambara, Tharcisse; Sabirov, Rushan M.

2016-01-01

Acquisition of dorsal structures, such as notochord and hollow nerve cord, is likely to have had a profound influence upon vertebrate evolution. Dorsal formation in chordate development thus has been intensively studied in vertebrates and ascidians. However, the present understanding does not explain how chordates acquired dorsal structures. Here we show that amphioxus retains a key clue to answer this question. In amphioxus embryos, maternal nodal mRNA distributes asymmetrically in accordance with the remodelling of the cortical cytoskeleton in the fertilized egg, and subsequently lefty is first expressed in a patch of blastomeres across the equator where wnt8 is expressed circularly and which will become the margin of the blastopore. The lefty domain co-expresses zygotic nodal by the initial gastrula stage on the one side of the blastopore margin and induces the expression of goosecoid, not-like, chordin and brachyury1 genes in this region, as in the oral ectoderm of sea urchin embryos, which provides a basis for the formation of the dorsal structures. The striking similarity in the gene regulations and their respective expression domains when comparing dorsal formation in amphioxus and the determination of the oral ectoderm in sea urchin embryos suggests that chordates derived from an ambulacrarian-type blastula with dorsoventral inversion. PMID:27307516

Transcriptome architecture across tissues in the pig

PubMed Central

Ferraz, André LJ; Ojeda, Ana; López-Béjar, Manel; Fernandes, Lana T; Castelló, Anna; Folch, Josep M; Pérez-Enciso, Miguel

2008-01-01

Background Artificial selection has resulted in animal breeds with extreme phenotypes. As an organism is made up of many different tissues and organs, each with its own genetic programme, it is pertinent to ask: How relevant is tissue in terms of total transcriptome variability? Which are the genes most distinctly expressed between tissues? Does breed or sex equally affect the transcriptome across tissues? Results In order to gain insight on these issues, we conducted microarray expression profiling of 16 different tissues from four animals of two extreme pig breeds, Large White and Iberian, two males and two females. Mixed model analysis and neighbor – joining trees showed that tissues with similar developmental origin clustered closer than those with different embryonic origins. Often a sound biological interpretation was possible for overrepresented gene ontology categories within differentially expressed genes between groups of tissues. For instance, an excess of nervous system or muscle development genes were found among tissues of ectoderm or mesoderm origins, respectively. Tissue accounted for ~11 times more variability than sex or breed. Nevertheless, we were able to confidently identify genes with differential expression across tissues between breeds (33 genes) and between sexes (19 genes). The genes primarily affected by sex were overall different than those affected by breed or tissue. Interaction with tissue can be important for differentially expressed genes between breeds but not so much for genes whose expression differ between sexes. Conclusion Embryonic development leaves an enduring footprint on the transcriptome. The interaction in gene × tissue for differentially expressed genes between breeds suggests that animal breeding has targeted differentially each tissue's transcriptome. PMID:18416811

Human somatic cells acquire the plasticity to generate embryoid-like metamorphosis via the actin cytoskeleton in injured tissues.

PubMed

Diaz, Jairo A; Murillo, Mauricio F; Mendoza, Jhonan A; Barreto, Ana M; Poveda, Lina S; Sanchez, Lina K; Poveda, Laura C; Mora, Katherine T

2016-01-01

Emergent biological responses develop via unknown processes dependent on physical collision. In hypoxia, when the tissue architecture collapses but the geometric core is stable, actin cytoskeleton filament components emerge, revealing a hidden internal order that identifies how each molecule is reassembled into the original mold, using one common connection, i.e., a fractal self-similarity that guides the system from the beginning in reverse metamorphosis, with spontaneous self-assembly of past forms that mimics an embryoid phenotype. We captured this hidden collective filamentous assemblage in progress: Hypoxic deformed cells enter into intercellular collisions, generate migratory ejected filaments, and produce self-assembly of triangular chiral hexagon complexes; this dynamic geometry guides the microenvironment scaffold in which this biological process is incubated, recapitulating embryonic morphogenesis. In all injured tissues, especially in damaged skeletal (striated) muscle cells, visibly hypertrophic intercalated actin-myosin filaments are organized in zebra stripe pattern along the anterior-posterior axis in the interior of the cell, generating cephalic-caudal polarity segmentation, with a high selective level of immunopositivity for Actin, Alpha Skeletal Muscle antibody and for Neuron-Specific Enolase expression of ectodermal differentiation. The function of actin filaments in emergent responses to tissue injury is to reconstitute, reactivate and orchestrate cellular metamorphosis, involving the re-expression of fetal genes, providing evidence of the reverse flow of genetic information within a biological system. The resultant embryoid phenotype emerges as a microscopic fractal template copy of the organization of the whole body, likely allowing the modification and reprogramming of the phenotype of the tumor in which these structures develop, as well as establishing a reverse primordial microscopic mold to collectively re-form cellular building blocks to regenerate injured tissues. Tumorigenesis mimics a self-organizing process of early embryo development. All malignant tumors produce fetal proteins, we now know from which these proteins proceed. Embryoid-like metamorphosis phenomena would represent the anatomical and functional entity of the injury stem cell niche. The sufficiently fast identification, isolation, culture, and expansion of these self-organized structures or genetically derived products could, in our opinion, be used to develop new therapeutic strategies against cancer and in regenerative medicine.

Human somatic cells acquire the plasticity to generate embryoid-like metamorphosis via the actin cytoskeleton in injured tissues

PubMed Central

Diaz, Jairo A; Murillo, Mauricio F; Mendoza, Jhonan A; Barreto, Ana M; Poveda, Lina S; Sanchez, Lina K; Poveda, Laura C; Mora, Katherine T

2016-01-01

Emergent biological responses develop via unknown processes dependent on physical collision. In hypoxia, when the tissue architecture collapses but the geometric core is stable, actin cytoskeleton filament components emerge, revealing a hidden internal order that identifies how each molecule is reassembled into the original mold, using one common connection, i.e., a fractal self-similarity that guides the system from the beginning in reverse metamorphosis, with spontaneous self-assembly of past forms that mimics an embryoid phenotype. We captured this hidden collective filamentous assemblage in progress: Hypoxic deformed cells enter into intercellular collisions, generate migratory ejected filaments, and produce self-assembly of triangular chiral hexagon complexes; this dynamic geometry guides the microenvironment scaffold in which this biological process is incubated, recapitulating embryonic morphogenesis. In all injured tissues, especially in damaged skeletal (striated) muscle cells, visibly hypertrophic intercalated actin-myosin filaments are organized in zebra stripe pattern along the anterior-posterior axis in the interior of the cell, generating cephalic-caudal polarity segmentation, with a high selective level of immunopositivity for Actin, Alpha Skeletal Muscle antibody and for Neuron-Specific Enolase expression of ectodermal differentiation. The function of actin filaments in emergent responses to tissue injury is to reconstitute, reactivate and orchestrate cellular metamorphosis, involving the re-expression of fetal genes, providing evidence of the reverse flow of genetic information within a biological system. The resultant embryoid phenotype emerges as a microscopic fractal template copy of the organization of the whole body, likely allowing the modification and reprogramming of the phenotype of the tumor in which these structures develop, as well as establishing a reverse primordial microscopic mold to collectively re-form cellular building blocks to regenerate injured tissues. Tumorigenesis mimics a self-organizing process of early embryo development. All malignant tumors produce fetal proteins, we now know from which these proteins proceed. Embryoid-like metamorphosis phenomena would represent the anatomical and functional entity of the injury stem cell niche. The sufficiently fast identification, isolation, culture, and expansion of these self-organized structures or genetically derived products could, in our opinion, be used to develop new therapeutic strategies against cancer and in regenerative medicine. PMID:27725917

Ectodermal dysplasias: A clinical classification and a causal review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pinheiro, M.; Freire-Maia, N.

1994-11-01

The authors present a causal review of 154 ectodermal dysplasias (EDs) as classified into 11 clinical subgroups. The number of EDs in each subgroup varies from one to 43. The numbers of conditions due to autosomal dominant, autosomal recessive, and X-linked genes are, respectively, 41, 52, and 8. In 53 conditions cause is unknown; 35 of them present some causal (genetic) suggestion.

The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

PubMed

LeBoeuf, Nicole; Garg, Amit; Worobec, Sophie

2007-01-01

The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome is characterized by the presence of chronic mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. Almost all patients have skin or nail findings early in the course of the disease. Therefore, the dermatologist is in the unique position of being able to identify patients with this syndrome early in its course and to facilitate careful monitoring of potentially lethal complications.

Maternal folic acid-deficient diet causes congenital malformations in the mouse eye.

PubMed

Maestro-de-las-Casas, Carmen; Pérez-Miguelsanz, Juliana; López-Gordillo, Yamila; Maldonado, Estela; Partearroyo, Teresa; Varela-Moreiras, Gregorio; Martínez-Álvarez, Concepción

2013-09-01

The eye is a very complex structure derived from the neural tube, surface ectoderm, and migratory mesenchyme from a neural crest origin. Because structures that evolve from the neural tube may be affected by a folate/folic acid (FA) deficiency, the aim of this work was to investigate whether a maternal folic acid-deficient diet may cause developmental alterations in the mouse eye. Female C57BL/6J mice (8 weeks old) were assigned into two different folic acid groups for periods ranging between 2 and 16 weeks. Animals were killed at gestation day 17. Hepatic folate was analyzed, and the eyes from 287 fetuses were macroscopically studied, sectioned and immunolabeled with anti-transforming growth factor (TGF)-β2 and anti-TGF-βRII. Mice exposed to a FA-deficient diet exhibited numerous eye macroscopic anomalies, such as anophthalmia and microphthalmia. Microscopically, the eye was the most affected organ (43.7% of the fetuses). The highest incidence of malformations occurred from the 8th week onward. A statistically significant linear association between the number of maternal weeks on the FA-deficient diet and embryonic microscopic eye malformations was observed. The optic cup derivatives and structures forming the eye anterior segment showed severe abnormalities. In addition, TGF-β2 and TGF-βRII expression in the eye was also altered. This study suggests that an adequate folic acid/folate status plays a key role in the formation of ocular tissues and structures, whereas a vitamin deficiency is negatively associated with a normal eye development even after a short-term exposure. Copyright © 2013 Wiley Periodicals, Inc.

The DP-1 transcription factor is required for keratinocyte growth and epidermal stratification.

PubMed

Chang, Wing Y; Bryce, Dawn M; D'Souza, Sudhir J A; Dagnino, Lina

2004-12-03

The epidermis is a stratified epithelium constantly replenished through the ability of keratinocytes in its basal layer to proliferate and self-renew. The epidermis arises from a single-cell layer ectoderm during embryogenesis. Large proliferative capacity is central to ectodermal cell and basal keratinocyte function. DP-1, a heterodimeric partner of E2F transcription factors, is highly expressed in the ectoderm and all epidermal layers during embryogenesis. To investigate the role of DP-1 in epidermal morphogenesis, we inhibited DP-1 activity through exogenous expression of a dominant-negative mutant (dnDP-1). Expression of the dnDP-1 mutant interferes with binding of E2F/DP-1 heterodimers to DNA and inhibits DNA replication, as well as cyclin A mRNA and protein expression. Chromatin immunoprecipitation analysis demonstrated that the cyclin A promoter is predominantly bound in proliferating keratinocytes by complexes containing E2F-3 and E2F-4. Thus, the mechanisms of decreased expression of cyclin A in the presence of dnDP-1 seem to involve inactivation of DP-1 complexes containing E2F-3 and E2F-4. To assess the consequences on epidermal morphogenesis of inhibiting DP-1 activity, we expressed dnDP-1 in rat epithelial keratinocytes in organotypic culture and observed that DP-1 inhibition negatively affected stratification of these cells. Likewise, expression of dnDP-1 in embryonic ectoderm explants produced extensive disorganization of subsequently formed epidermal basal and suprabasal layers, interfering with normal epidermal formation. We conclude that DP-1 activity is required for normal epidermal morphogenesis and ectoderm-to-epidermis transition.

The evolutionary history of vertebrate cranial placodes II. Evolution of ectodermal patterning.

PubMed

Schlosser, Gerhard; Patthey, Cedric; Shimeld, Sebastian M

2014-05-01

Cranial placodes are evolutionary innovations of vertebrates. However, they most likely evolved by redeployment, rewiring and diversification of preexisting cell types and patterning mechanisms. In the second part of this review we compare vertebrates with other animal groups to elucidate the evolutionary history of ectodermal patterning. We show that several transcription factors have ancient bilaterian roles in dorsoventral and anteroposterior regionalisation of the ectoderm. Evidence from amphioxus suggests that ancestral chordates then concentrated neurosecretory cells in the anteriormost non-neural ectoderm. This anterior proto-placodal domain subsequently gave rise to the oral siphon primordia in tunicates (with neurosecretory cells being lost) and anterior (adenohypophyseal, olfactory, and lens) placodes of vertebrates. Likewise, tunicate atrial siphon primordia and posterior (otic, lateral line, and epibranchial) placodes of vertebrates probably evolved from a posterior proto-placodal region in the tunicate-vertebrate ancestor. Since both siphon primordia in tunicates give rise to sparse populations of sensory cells, both proto-placodal domains probably also gave rise to some sensory receptors in the tunicate-vertebrate ancestor. However, proper cranial placodes, which give rise to high density arrays of specialised sensory receptors and neurons, evolved from these domains only in the vertebrate lineage. We propose that this may have involved rewiring of the regulatory network upstream and downstream of Six1/2 and Six4/5 transcription factors and their Eya family cofactors. These proteins, which play ancient roles in neuronal differentiation were first recruited to the dorsal non-neural ectoderm in the tunicate-vertebrate ancestor but subsequently probably acquired new target genes in the vertebrate lineage, allowing them to adopt new functions in regulating proliferation and patterning of neuronal progenitors. Copyright © 2014 Elsevier Inc. All rights reserved.

A Novel Homozygous Missense Mutation in HOXC13 Leads to Autosomal Recessive Pure Hair and Nail Ectodermal Dysplasia.

PubMed

Li, Xiaoxiao; Orseth, Meredith Lee; Smith, J Michael; Brehm, Mary Abigail; Agim, Nnenna Gebechi; Glass, Donald Alexander

2017-03-01

Pure hair and nail ectodermal dysplasia (PHNED) is a rare disorder that presents with hypotrichosis and nail dystrophy while sparing other ectodermal structures such as teeth and sweat glands. We describe a homozygous novel missense mutation in the HOXC13 gene that resulted in autosomal recessive PHNED in a Hispanic child. The mutation c.812A>G (p.Gln271Arg) is located within the DNA-binding domain of the HOXC13 gene, cosegregates within the family, and is predicted to be maximally damaging. This is the first reported case of a missense HOXC13 mutation resulting in PHNED and the first reported case of PHNED identified in a North American family. Our findings illustrate the critical role of HOXC13 in human hair and nail development. © 2017 Wiley Periodicals, Inc.

A novel homozygous missense variant in NECTIN4 (PVRL4) causing ectodermal dysplasia cutaneous syndactyly syndrome.

PubMed

Ahmad, Farooq; Nasir, Abdul; Thiele, Holger; Umair, Muhammad; Borck, Guntram; Ahmad, Wasim

2018-02-12

Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare form of ectodermal dysplasia including anomalies of hair, nails, and teeth along with bilateral cutaneous syndactyly of hands and feet. In the present report, we performed a clinical and genetic characterization of a consanguineous Pakistani family with four individuals affected by EDSS1. We performed exome sequencing using DNA of one affected individual. Exome data analysis identified a novel homozygous missense variant (c.242T>C; p.(Leu81Pro)) in NECTIN4 (PVRL4). Sanger sequencing validated this variant and confirmed its cosegregation with the disease phenotype in the family members. Thus, our report adds a novel variant to the NECTIN4 mutation spectrum and contributes to the NECTIN4-related clinical characterization. © 2018 John Wiley & Sons Ltd/University College London.

Ectodermal fragments from normal frog gastrulae condition substrata to support normal and hybrid mesodermal cell migration in vitro.

PubMed

Nakatsuji, N; Johnson, K E

1984-06-01

Using time-lapse cinemicrography and scanning electron microscopy, we have shown that normal Rana embryos and gastrulating hybrid embryos have extracellular fibrils on the inner surface of the ectodermal layer. These fibrils are absent prior to gastrulation and appear in increasing numbers during gastrulation. They can also be deposited in vitro where they condition substrata in such a way that normal presumptive mesodermal cells placed on them show extensive attachment and unoriented cell movement. These fibrils are also present in some arrested hybrid embryos, but in reduced numbers, or are lacking in other arrested hybrid embryos. Explanted ectodermal fragments from arrested hybrid embryos fail both to condition culture substrata by the deposition of fibrils and to promote cell attachment and translocation. In contrast, ectodermal fragments from normal embryos can condition culture substrata so as to promote moderate cell attachment and, for one particular gamete combination, even cell translocation of presumptive mesodermal cells taken from arrested hybrid embryos. These results provide new evidence to support the hypothesis that extracellular fibrils represent a system that promotes mesodermal cell migration in amphibian embryos. Differences in the fibrillar system in urodele and anuran embryos are discussed in relation to fundamental differences in the mode of mesodermal cell migration in these two classes of Amphibia.

Hypohidrotic ectodermal dysplasia, osteopetrosis, lymphedema, and immunodeficiency in an infant with multiple opportunistic infections.

PubMed

Carlberg, Valerie M; Lofgren, Sabra M; Mann, Julianne A; Austin, Jared P; Nolt, Dawn; Shereck, Evan B; Davila-Saldana, Blachy; Zonana, Jonathan; Krol, Alfons L

2014-01-01

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections. © 2013 Wiley Periodicals, Inc.

Analysis of Msx1; Msx2 double mutants reveals multiple roles for Msx genes in limb development.

PubMed

Lallemand, Yvan; Nicola, Marie-Anne; Ramos, Casto; Bach, Antoine; Cloment, Cécile Saint; Robert, Benoît

2005-07-01

The homeobox-containing genes Msx1 and Msx2 are highly expressed in the limb field from the earliest stages of limb formation and, subsequently, in both the apical ectodermal ridge and underlying mesenchyme. However, mice homozygous for a null mutation in either Msx1 or Msx2 do not display abnormalities in limb development. By contrast, Msx1; Msx2 double mutants exhibit a severe limb phenotype. Our analysis indicates that these genes play a role in crucial processes during limb morphogenesis along all three axes. Double mutant limbs are shorter and lack anterior skeletal elements (radius/tibia, thumb/hallux). Gene expression analysis confirms that there is no formation of regions with anterior identity. This correlates with the absence of dorsoventral boundary specification in the anterior ectoderm, which precludes apical ectodermal ridge formation anteriorly. As a result, anterior mesenchyme is not maintained, leading to oligodactyly. Paradoxically, polydactyly is also frequent and appears to be associated with extended Fgf activity in the apical ectodermal ridge, which is maintained up to 14.5 dpc. This results in a major outgrowth of the mesenchyme anteriorly, which nevertheless maintains a posterior identity, and leads to formation of extra digits. These defects are interpreted in the context of an impairment of Bmp signalling.

Personalized Stem Cell Therapy to Correct Corneal Defects Due to a Unique Homozygous-Heterozygous Mosaicism of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome.

PubMed

Barbaro, Vanessa; Nasti, Annamaria Assunta; Raffa, Paolo; Migliorati, Angelo; Nespeca, Patrizia; Ferrari, Stefano; Palumbo, Elisa; Bertolin, Marina; Breda, Claudia; Miceli, Francesco; Russo, Antonella; Caenazzo, Luciana; Ponzin, Diego; Palù, Giorgio; Parolin, Cristina; Di Iorio, Enzo

2016-08-01

: Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome is a rare autosomal dominant disease caused by mutations in the p63 gene. To date, approximately 40 different p63 mutations have been identified, all heterozygous. No definitive treatments are available to counteract and resolve the progressive corneal degeneration due to a premature aging of limbal epithelial stem cells. Here, we describe a unique case of a young female patient, aged 18 years, with EEC and corneal dysfunction, who was, surprisingly, homozygous for a novel and de novo R311K missense mutation in the p63 gene. A detailed analysis of the degree of somatic mosaicism in leukocytes from peripheral blood and oral mucosal epithelial stem cells (OMESCs) from biopsies of buccal mucosa showed that approximately 80% were homozygous mutant cells and 20% were heterozygous. Cytogenetic and molecular analyses excluded genomic alterations, thus suggesting a de novo mutation followed by an allelic gene conversion of the wild-type allele by de novo mutant allele as a possible mechanism to explain the homozygous condition. R311K-p63 OMESCs were expanded in vitro and heterozygous holoclones selected following clonal analysis. These R311K-p63 OMESCs were able to generate well-organized and stratified epithelia in vitro, resembling the features of healthy tissues. This study supports the rationale for the development of cultured autologous oral mucosal epithelial stem cell sheets obtained by selected heterozygous R311K-p63 stem cells, as an effective and personalized therapy for reconstructing the ocular surface of this unique case of EEC syndrome, thus bypassing gene therapy approaches. This case demonstrates that in a somatic mosaicism context, a novel homozygous mutation in the p63 gene can arise as a consequence of an allelic gene conversion event, subsequent to a de novo mutation. The heterozygous mutant R311K-p63 stem cells can be isolated by means of clonal analysis and given their good regenerative capacity, they may be used to successfully correct the corneal defects present in this unique case of ectrodactyly-ectodermal dysplasia-clefting syndrome. ©AlphaMed Press.

Density Banding in Coral Skeletons: A Biotic Response to Sea Surface Temperature?

NASA Astrophysics Data System (ADS)

Hill, C. A.; Oehlert, A. M.; Piggot, A. M.; Yau, P. M.; Fouke, B. W.

2008-12-01

Density bands in the CaCO3 (aragonite) skeleton of scleractinian corals are commonly used as chronometers, where crystalline couplets of high and low density bands represent the span of one year. This provides a sensitive reconstructive tool for paleothermometry, paleoclimatology and paleoecology. However, the detailed mechanisms controlling aragonite nucleation and crystallization events and the rate of skeletal growth remain uncertain. The organic matrix, composed of macromolecules secreted by the calicoblastic ectoderm, is closely associated with skeletal precipitation and is itself incorporated into the skeleton. We postulate that density banding is primarily controlled by changes in the rate of aragonite crystal precipitation mediated by the coral holobiont response to changes in sea surface temperature (SST). To test this hypothesis, data were collected from coral skeleton-tissue biopsies (2.5 cm in diameter) extracted from four species of Montastraea growing on the fringing reef tract of Curacao, Netherlands Antilles (annual mean variation in SST is 29° C in mid-September to 26° C in late February). Samples were collected in the following three contextual modes: 1) at two sites (Water Plant and Playa Kalki) along a lateral 25 km spatial transect; 2) across a vertical bathymetric gradient from 5 to 15 m water depth at each site; and 3) at strategic time periods spanning the 3° C annual variations in SST. Preliminary results indicate that skeletal density banding is also expressed in the organic matrix, permitting biochemical characterization and correlation of the organic matrix banding to the skeletal banding. In addition, both surficial and ectodermal mucins were characterized in terms of total protein content, abundance and location of their anionic, cationic, and neutral macromolecular constituents. Furthermore, the ratio of mucocytes in the oral ectoderm to gastrodermal symbiotic zooxanthellae has permitted estimates of seasonal carbon allocation by the coral holobiont. Our nanometer-scale optical analyses of crystal morphology, arrangement, and densities have revealed consistent changes between high and low skeletal density bands. Mass spectrometry, newly developed immunohistochemical staining, fluorescence and polarized light microscopy are in progress to further quantify and model these observations.

Herediatary anhidrotic ectodermal dysplasia. Studies in a Nigerian famil.

PubMed

Familusi, J B; Jaiyesimi, F; Ojo, C O; Attah, E B

1975-08-01

Studies in a Nigerian family with hereditary anhidrous ectodermal dysplasia are reported. Microscopical examinations of finger tips for sweat pores were diagnostic in phenotypes, and it is suggested that this simple nonsurgical procedure is a preferred alternative to skin biopsies in the diagnosis of the syndrome. The clinical implications of a tropical environment for the syndrome, as well as the factors that may favour maintenance of the gene in such an environment are discussed.

Irregular chiasm-C-roughest, a member of the immunoglobulin superfamily, affects sense organ spacing on the Drosophila antenna by influencing the positioning of founder cells on the disc ectoderm.

PubMed

Venugopala Reddy, G; Reiter, C; Shanbhag, S; Fischbach, K F; Rodrigues, V

1999-10-01

We describe a role for Irregular chiasmC-roughest (IrreC-rst), an immunoglobulin (Ig) superfamily member, in patterning sense organs on the Drosophila antenna. IrreC-rst protein is initially expressed homogeneously on apical profiles of ectodermal cells in regions of the antennal disc. During specification of founder cells (FCs), the intracellular protein distribution changes and becomes concentrated in regions where specific intercellular contacts presumably occur. Loss of function mutations as well as misexpression of irreC-rst results in an altered arrangement of FCs within the disc compared to wildtype. Sense organ development occurs normally, although spacing is affected. Unlike its role in interommatidial spacing, irreC-rst does not affect apoptosis during antennal development. We propose that IrreC-rst affects the spatial relationship between sensory and ectodermal cells during FC delamination.

Hand in glove: brain and skull in development and dysmorphogenesis

PubMed Central

Flaherty, Kevin

2013-01-01

The brain originates relatively early in development from differentiated ectoderm that forms a hollow tube and takes on an exceedingly complex shape with development. The skull is made up of individual bony elements that form from neural crest- and mesoderm-derived mesenchyme that unite to provide support and protection for soft tissues and spaces of the head. The meninges provide a protective and permeable membrane between brain and skull. Across evolutionary and developmental time, dynamic changes in brain and skull shape track one another so that their integration is evidenced in two structures that fit soundly regardless of changes in biomechanical and physiologic functions. Evidence for this tight correspondence is also seen in diseases of the craniofacial complex that are often classified as diseases of the skull (e.g., craniosynostosis) or diseases of the brain (e.g., holoprosencephaly) even when both tissues are affected. Our review suggests a model that links brain and skull morphogenesis through coordinated integration of signaling pathways (e.g., FGF, TGFβ, Wnt) via processes that are not currently understood, perhaps involving the meninges. Differences in the earliest signaling of biological structure establish divergent designs that will be enhanced during morphogenesis. Signaling systems that pattern the developing brain are also active in patterning required for growth and assembly of the skull and some members of these signaling families have been indicated as causal for craniofacial diseases. Because cells of early brain and skull are sensitive to similar signaling families, variation in the strength or timing of signals or shifts in patterning boundaries that affect one system (neural or skull) could also affect the other system and appropriate co-adjustments in development would be made. Interactions of these signaling systems and of the tissues that they pattern are fundamental to the consistent but labile functional and structural association of brain and skull conserved over evolutionary time obvious in the study of development and disease. PMID:23525521

SNW1 Is a Critical Regulator of Spatial BMP Activity, Neural Plate Border Formation, and Neural Crest Specification in Vertebrate Embryos

PubMed Central

Wu, Mary Y.; Ramel, Marie-Christine; Howell, Michael; Hill, Caroline S.

2011-01-01

Bone morphogenetic protein (BMP) gradients provide positional information to direct cell fate specification, such as patterning of the vertebrate ectoderm into neural, neural crest, and epidermal tissues, with precise borders segregating these domains. However, little is known about how BMP activity is regulated spatially and temporally during vertebrate development to contribute to embryonic patterning, and more specifically to neural crest formation. Through a large-scale in vivo functional screen in Xenopus for neural crest fate, we identified an essential regulator of BMP activity, SNW1. SNW1 is a nuclear protein known to regulate gene expression. Using antisense morpholinos to deplete SNW1 protein in both Xenopus and zebrafish embryos, we demonstrate that dorsally expressed SNW1 is required for neural crest specification, and this is independent of mesoderm formation and gastrulation morphogenetic movements. By exploiting a combination of immunostaining for phosphorylated Smad1 in Xenopus embryos and a BMP-dependent reporter transgenic zebrafish line, we show that SNW1 regulates a specific domain of BMP activity in the dorsal ectoderm at the neural plate border at post-gastrula stages. We use double in situ hybridizations and immunofluorescence to show how this domain of BMP activity is spatially positioned relative to the neural crest domain and that of SNW1 expression. Further in vivo and in vitro assays using cell culture and tissue explants allow us to conclude that SNW1 acts upstream of the BMP receptors. Finally, we show that the requirement of SNW1 for neural crest specification is through its ability to regulate BMP activity, as we demonstrate that targeted overexpression of BMP to the neural plate border is sufficient to restore neural crest formation in Xenopus SNW1 morphants. We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate border formation and thus neural crest specification. PMID:21358802

Identification and characterization of mouse otic sensory lineage genes

PubMed Central

Hartman, Byron H.; Durruthy-Durruthy, Robert; Laske, Roman D.; Losorelli, Steven; Heller, Stefan

2015-01-01

Vertebrate embryogenesis gives rise to all cell types of an organism through the development of many unique lineages derived from the three primordial germ layers. The otic sensory lineage arises from the otic vesicle, a structure formed through invagination of placodal non-neural ectoderm. This developmental lineage possesses unique differentiation potential, giving rise to otic sensory cell populations including hair cells, supporting cells, and ganglion neurons of the auditory and vestibular organs. Here we present a systematic approach to identify transcriptional features that distinguish the otic sensory lineage (from early otic progenitors to otic sensory populations) from other major lineages of vertebrate development. We used a microarray approach to analyze otic sensory lineage populations including microdissected otic vesicles (embryonic day 10.5) as well as isolated neonatal cochlear hair cells and supporting cells at postnatal day 3. Non-otic tissue samples including periotic tissues and whole embryos with otic regions removed were used as reference populations to evaluate otic specificity. Otic populations shared transcriptome-wide correlations in expression profiles that distinguish members of this lineage from non-otic populations. We further analyzed the microarray data using comparative and dimension reduction methods to identify individual genes that are specifically expressed in the otic sensory lineage. This analysis identified and ranked top otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and additional novel otic lineage markers. To validate these results we performed expression analysis on select genes using immunohistochemistry and in situ hybridization. Fbxo2 showed the most striking pattern of specificity to the otic sensory lineage, including robust expression in the early otic vesicle and sustained expression in prosensory progenitors and auditory and vestibular hair cells and supporting cells. PMID:25852475

The Corneal Epithelial Barrier and Its Developmental Role in Isolating Corneal Epithelial and Conjunctival Cells From One Another

PubMed Central

Kubilus, James K.; Zapater i Morales, Carolina; Linsenmayer, Thomas F.

2017-01-01

Purpose During development, the corneal epithelium (CE) and the conjunctiva are derived from the surface ectoderm. Here we have examined how, during development, the cells of these two issues become isolated from each other. Methods Epithelia from the anterior eyes of chicken embryos were labeled with the fluorescent, lipophilic dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). DiI was placed on the epithelial surface of the developing anterior eye and its diffusion was monitored by fluorescence microscopy. Concomitant morphologic changes in the surface cells of these epithelial were examined by scanning electron microscopy. Immunofluorescence was used to analyze the expression of cytokeratin K3, ZO-1, N-cadherin and Connexin-43 and the function of gap junctions was analyzed using a cut-loading with the fluorescent dye rhodamine-dextran. Results Prior to embryonic day 8 (E8), DiI placed on the surface of the CE spreads throughout all the epithelial cells of the anterior eye. When older eyes were similarly labeled, dye diffusion was restricted to the CE. Similarly, diffusion of DiI placed on the conjunctival surface after E8 was restricted to the conjunctiva. Scanning electron microscopy showed that developmentally (1) physical separations progressively form between the cells of the CE and those of the conjunctiva, and (2) by E8 these separations form a ring that completely encompasses the cornea. The functional restriction of gap junctions between these tissues did not occur until E14. Conclusions During ocular development, a barrier to the diffusion of DiI forms between the contiguous CE and conjunctiva prior to the differential expression of gap junctions within these tissues. PMID:28319640

Herpes: a dilemma for client and clinician.

PubMed

Edlund, B J; Poteet, G W

1987-01-01

In the last 10 years genital herpes simplex has reached epidemic proportions, affecting 5 million Americans, with 500,000 new cases yearly. The incidence is highest among middle and upper socioeconomic groups and among whites. There are 2 antigenically distinct strains of the herpes simplex virus, and type II is the cause of 85% of the genital infections. The virus has an affinity for tissues derived from the embryonic ectoderm -- skin, mucous membranes, eye, and central nervous system. Transmission is by personal contact with an infected area. The clinical course of the disease involves 4 stages. In the primary stage the typical lesions are vesicles, which rupture, leaving painful shallow ulcerations. The primary stage lasts from 2 to 4 weeks with approximately 10 days of viral shedding. In the latent stage the virus lies dormant in the sacral ganglion and is noninfectious. In the shedding stage the virus replicates and sheds in genital secretions. The recurrent stage is characterized by prodromal itching or tingling sensations prior to the eruption of the vesicles and by neuralgia. Recurrence occurs as often as 4 to 7 times a year and lasts from 7 to 10 days, with viral shedding for 4 or 5 days. Definitive diagnosis can be made from viral tissue culture or the Tzanck and Papanicolaou smears. There is no cure for herpes although acyclovir has been found to shorten the duration of the episodes. Except for pregnancy complications, the most serious complications of recurrent genital herpes are psychological. The disease is socially stigmatizing and inhibits sexual activity. The nurse should provide supportive care, information about the transmission and symptoms of the disease, and counseling as to precautions to take, such as condom and spermicide use, avoidance of oral sex, abstention when lesions are present, and limiting sex to one partner.

Evolution of bilaterian central nervous systems: a single origin?

PubMed Central

2013-01-01

The question of whether the ancestral bilaterian had a central nervous system (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable evidence supports the theory that a CNS evolved just once. However, an alternative view proposes that the chordate CNS evolved from the ectodermal nerve net of a hemichordate-like ancestral deuterostome, implying independent evolution of the CNS in chordates and protostomes. To specify morphological divisions along the anterior/posterior axis, this ancestor used gene networks homologous to those patterning three organizing centers in the vertebrate brain: the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent evolution of the vertebrate brain involved elaboration of these ancestral signaling centers; however, all or part of these signaling centers were lost from the CNS of invertebrate chordates. The present review analyzes the evidence for and against these theories. The bulk of the evidence indicates that a CNS evolved just once – in the ancestral bilaterian. Importantly, in both protostomes and deuterostomes, the CNS represents a portion of a generally neurogenic ectoderm that is internalized and receives and integrates inputs from sensory cells in the remainder of the ectoderm. The expression patterns of genes involved in medio/lateral (dorso/ventral) patterning of the CNS are similar in protostomes and chordates; however, these genes are not similarly expressed in the ectoderm outside the CNS. Thus, their expression is a better criterion for CNS homologs than the expression of anterior/posterior patterning genes, many of which (for example, Hox genes) are similarly expressed both in the CNS and in the remainder of the ectoderm in many bilaterians. The evidence leaves hemichordates in an ambiguous position – either CNS centralization was lost to some extent at the base of the hemichordates, or even earlier, at the base of the hemichordates + echinoderms, or one of the two hemichordate nerve cords is homologous to the CNS of protostomes and chordates. In any event, the presence of part of the genetic machinery for the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer in invertebrate chordates together with similar morphology indicates that these organizers were present, at least in part, at the base of the chordates and were probably elaborated upon in the vertebrate lineage. PMID:24098981

Embryonic development of chicken (Gallus Gallus Domesticus) from 1st to 19th day-ectodermal structures.

PubMed

Toledo Fonseca, Erika; De Oliveira Silva, Fernanda Menezes; Alcântara, Dayane; Carvalho Cardoso, Rafael; Luís Franciolli, André; Sarmento, Carlos Alberto Palmeira; Fratini, Paula; José Piantino Ferreira, Antônio; Miglino, Maria Angélica

2013-12-01

Birds occupy a prominent place in the Brazilian economy not only in the poultry industry but also as an animal model in many areas of scientific research. Thus the aim of this study was to provide a description of macro and microscopic aspects of the ectoderm-derived structures in chicken embryos / fetuses poultry (Gallus gallus domesticus) from 1st to 19th day of incubation. 40 fertilized eggs, from a strain of domestic chickens, with an incubation period of 2-19 days were subjected to macroscopic description, biometrics, light, and scanning microscopy. All changes observed during the development were described. The nervous system, skin and appendages and organs related to vision and hearing began to be identified, both macro and microscopically, from the second day of incubation. The vesicles from the primitive central nervous system-forebrain, midbrain, and hindbrain-were identified on the third day of incubation. On the sixth day of incubation, there was a clear vascularization of the skin. The optic vesicle was first observed fourth day of development and on the fifth day there was the beginning of the lens formation. Although embryonic development is influenced by animal line as well as external factors such as incubation temperature, this paper provides a chronological description for chicken (Gallus gallus domesticus) during its embryonic development. Copyright © 2013 Wiley Periodicals, Inc.

Cloning of the anhidrotic ectodermal dysplasia gene: Identification of cDNAs associated with CpG islands mapped near translocation breakpoint in two female patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, A.K.; Schlessinger, D.; Kere, J.

1994-09-01

The gene for the X chromosomal developmental disorder anhidrotic ectodermal dysplasia (EDA) has been mapped to Xq12-q13 by linkage analysis and is expressed in a few females with chromosomal translocations involving band Xq12-q13. A yeast artificial chromosome (YAC) contig (2.0 Mb) spanning two translocation breakpoints has been assembled by sequence-tagged site (STS)-based chromosomal walking. The two translocation breakpoints (X:autosome translocations from the affected female patients) have been mapped less than 60 kb apart within a YAC contig. Unique probes and intragenic STSs (mapped between the two translocations) have been developed and a somatic cell hybrid carrying the translocated X chromosomemore » from the AK patient has been analyzed by isolating unique probes that span the breakpoint. Several STSs made from intragenic sequences have been found to be conserved in mouse, hamster and monkey, but we have detected no mRNAs in a number of tissues tested. However, a probe and STS developed from the DNA spanning the AK breakpoint is conserved in mouse, hamster and monkey, and we have detected expressed sequences in skin cells and cDNA libraries. In addition, unique sequences have been obtained from two CpG islands in the region that maps proximal to the breakpoints. cDNAs containing these sequences are being studied as candidates for the gene affected in the etiology of EDA.« less

The embryologic development of the human external auditory meatus. Preliminary report.

PubMed

Nishimura, Y; Kumoi, T

1992-01-01

During the final period of embryogenesis, a funnel-shaped tube continues medially into the mesenchymal tissue forming a curved path. Although this may sound simple, the development occurring during early fetal life is in fact very complex. At first, ectodermal cells proliferate to fill the lumen of the meatus, forming the meatal plug, and then at 10 weeks the bottom of the plug extends in a disc-like fashion, so that in the horizontal plane the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. At the same time, the plug in the proximal portion of the neck starts to be resorbed. In the 13-week fetus, the disc-like plug begins to show signs of its final destiny; the innermost surface of the plug in contact with the anlage of the malleus is ready to contribute to the formation of the tympanic membrane. In the 15-week fetus, the innermost portion of the disc-like plug splits, leaving a thin ectodermal cell layer of immature tympanic membrane. The neck of the boot forms the border between the primary and secondary meatus, and is the last part to split. In the 16.5-week fetus, the meatus is fully patent throughout its entire length, although the lumen is still narrow and curved. In the 18-week fetus, the meatus is already fully expanded to its complete form.

Large, long range tensile forces drive convergence during Xenopus blastopore closure and body axis elongation

PubMed Central

Kasprowicz, Eric M; Davidson, Lance A; Keller, Raymond

2018-01-01

Indirect evidence suggests that blastopore closure during gastrulation of anamniotes, including amphibians such as Xenopus laevis, depends on circumblastoporal convergence forces generated by the marginal zone (MZ), but direct evidence is lacking. We show that explanted MZs generate tensile convergence forces up to 1.5 μN during gastrulation and over 4 μN thereafter. These forces are generated by convergent thickening (CT) until the midgastrula and increasingly by convergent extension (CE) thereafter. Explants from ventralized embryos, which lack tissues expressing CE but close their blastopores, produce up to 2 μN of tensile force, showing that CT alone generates forces sufficient to close the blastopore. Uniaxial tensile stress relaxation assays show stiffening of mesodermal and ectodermal tissues around the onset of neurulation, potentially enhancing long-range transmission of convergence forces. These results illuminate the mechanobiology of early vertebrate morphogenic mechanisms, aid interpretation of phenotypes, and give insight into the evolution of blastopore closure mechanisms. PMID:29533180

Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers.

PubMed

Bergstralh, Dan T; Lovegrove, Holly E; St Johnston, Daniel

2015-11-01

Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium. Here we test this assumption in three types of Drosophila epithelium; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells seems to be driven by lateral adhesion, which pulls cells born outside the epithelial layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions.

Enamel: Molecular identity of its transepithelial ion transport system.

PubMed

Lacruz, Rodrigo S

2017-07-01

Enamel is the most calcified tissue in vertebrates. It differs from bone in a number of characteristics including its origin from ectodermal epithelium, lack of remodeling capacity by the enamel forming cells, and absence of collagen. The enamel-forming cells known as ameloblasts, choreograph first the synthesis of a unique protein-rich matrix, followed by the mineralization of this matrix into a tissue that is ∼95% mineral. To do this, ameloblasts arrange the coordinated movement of ions across a cell barrier while removing matrix proteins and monitoring extracellular pH using a variety of buffering systems to enable the growth of carbonated apatite crystals. Although our knowledge of these processes and the molecular identity of the proteins involved in transepithelial ion transport has increased in the last decade, it remains limited compared to other cells. Here we present an overview of the evolution and development of enamel, its differences with bone, and describe the ion transport systems associated with ameloblasts. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Id expression in amphioxus and lamprey highlights the role of gene cooption during neural crest evolution

NASA Technical Reports Server (NTRS)

Meulemans, Daniel; McCauley, David; Bronner-Fraser, Marianne

2003-01-01

Neural crest cells are unique to vertebrates and generate many of the adult structures that differentiate them from their closest invertebrate relatives, the cephalochordates. Id genes are robust markers of neural crest cells at all stages of development. We compared Id gene expression in amphioxus and lamprey to ask if cephalochordates deploy Id genes at the neural plate border and dorsal neural tube in a manner similar to vertebrates. Furthermore, we examined whether Id expression in these cells is a basal vertebrate trait or a derived feature of gnathostomes. We found that while expression of Id genes in the mesoderm and endoderm is conserved between amphioxus and vertebrates, expression in the lateral neural plate border and dorsal neural tube is a vertebrate novelty. Furthermore, expression of lamprey Id implies that recruitment of Id genes to these cells occurred very early in the vertebrate lineage. Based on expression in amphioxus we postulate that Id cooption conferred sensory cell progenitor-like properties upon the lateral neurectoderm, and pharyngeal mesoderm-like properties upon cranial neural crest. Amphioxus Id expression is also consistent with homology between the anterior neurectoderm of amphioxus and the presumptive placodal ectoderm of vertebrates. These observations support the idea that neural crest evolution was driven in large part by cooption of multipurpose transcriptional regulators from other tissues and cell types.

Pluripotency of adult stem cells derived from human and rat pancreas

NASA Astrophysics Data System (ADS)

Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

Cell fusion phenomena detected after in utero transplantation of Ds-red-harboring porcine amniotic fluid stem cells into EGFP transgenic mice.

PubMed

Peng, Shao-Yu; Chen, Yu-Hsu; Chou, Chih-Jen; Wang, Yao-Horng; Lee, Hung-Maan; Cheng, Winston Teng-Kui; Shaw, S W Steven; Wu, Shinn-Chih

2014-05-01

Amniotic fluid stem cells (AFSCs) are derived from the amniotic fluid of the developing fetus and can give rise to diverse differentiated cells of ectoderm, mesoderm, and endoderm lineages. Intrauterine transplantation is an approach used to cure inherited genetic fetal defects during the gestation period of pregnant dams. Certain disease such as osteogenesis imperfecta was successfully treated in affected fetal mice using this method. However, the donor cell destiny remains uncertain. The purpose of this study was to investigate the biodistribution and cell fate of Ds-red-harboring porcine AFSCs (Ds-red pAFSCs) after intrauterine transplantation into enhanced green fluorescent protein-harboring fetuses of pregnant mice. Pregnant mice (12.5 days) underwent open laparotomy with intrauterine pAFSC transplantation (5 × 10(4) cells per pup) into fetal peritoneal cavity. Three weeks after birth, the mice were sacrificed. Several samples from different organs were obtained for histological examination and flow cytometric analysis. Ds-red pAFSCs migrated most frequently into the intestines. Furthermore, enhanced green fluorescent protein and red fluorescent protein signals were co-expressed in the intestine and liver cells via immunohistochemistry studies. In utero xenotransplantation of pAFSCs fused with recipient intestinal cells instead of differentiating or maintaining the undifferentiated status in the tissue. © 2014 John Wiley & Sons, Ltd.

The receptor tyrosine kinase Pvr promotes tissue closure by coordinating corpse removal and epidermal zippering

PubMed Central

Garlena, Rebecca A.; Lennox, Ashley L.; Baker, Lewis R.; Parsons, Trish E.; Weinberg, Seth M.; Stronach, Beth E.

2015-01-01

A leading cause of human birth defects is the incomplete fusion of tissues, often manifested in the palate, heart or neural tube. To investigate the molecular control of tissue fusion, embryonic dorsal closure and pupal thorax closure in Drosophila are useful experimental models. We find that Pvr mutants have defects in dorsal midline closure with incomplete amnioserosa internalization and epidermal zippering, as well as cardia bifida. These defects are relatively mild in comparison to those seen with other signaling mutants, such as in the JNK pathway, and we demonstrate that JNK signaling is not perturbed by altering Pvr receptor tyrosine kinase activity. Rather, modulation of Pvr levels in the ectoderm has an impact on PIP3 membrane accumulation, consistent with a link to PI3K signal transduction. Polarized PI3K activity influences protrusive activity from the epidermal leading edge and the protrusion area changes in accord with Pvr signaling intensity, providing a possible mechanism to explain Pvr mutant phenotypes. Tissue-specific rescue experiments indicate a partial requirement in epithelial tissue, but confirm the essential role of Pvr in hemocytes for embryonic survival. Taken together, we argue that inefficient removal of the internalizing amnioserosa tissue by mutant hemocytes coupled with impaired midline zippering of mutant epithelium creates a situation in some embryos whereby dorsal midline closure is incomplete. Based on these observations, we suggest that efferocytosis (corpse clearance) could contribute to proper tissue closure and thus might underlie some congenital birth defects. PMID:26293306

The formation of the avian scapula blade takes place in the hypaxial domain of the somites and requires somatopleure-derived BMP signals.

PubMed

Wang, Baigang; He, Liwen; Ehehalt, Florian; Geetha-Loganathan, Poongodi; Nimmagadda, Suresh; Christ, Bodo; Scaal, Martin; Huang, Ruijin

2005-11-01

The avian scapula is a long bone located dorsally on the thorax. The cranial part that articulates with the upper limb is derived from the somatopleure of the forelimb field, while the caudal part, the scapula blade, originates from the dermomyotomes of brachial and thoracic somites. In previous studies, we have shown that scapula blade formation is intrinsically controlled by segment-specific information as well as extrinsically by ectoderm-derived signals. Here, we addressed the role of signals derived from the lateral plate mesoderm on scapula development. Chick-quail chimera experiments revealed that scapula precursor cells are located within the hypaxial domain of the dermomyotome adjacent to somatopleural cells. Barrier implantation between these two cell populations inhibited scapula blade formation. Furthermore, we identified BMPs as scapula-inducing signals from the somatopleure using injection of Noggin-producing cells into the hypaxial domain of scapula-forming dermomyotomes. We found that inhibition of BMP activity interfered with scapula-specific Pax1 expression and scapula blade formation. Taken together, we demonstrate that the scapula-forming cells located within the hypaxial somitic domain require BMP signals derived from the somatopleure for their specification and differentiation.

DNA methylation in schizophrenia in different patient-derived cell types.

PubMed

Vitale, Alejandra M; Matigian, Nicholas A; Cristino, Alexandre S; Nones, Katia; Ravishankar, Sugandha; Bellette, Bernadette; Fan, Yongjun; Wood, Stephen A; Wolvetang, Ernst; Mackay-Sim, Alan

2017-01-01

DNA methylation of gene promoter regions represses transcription and is a mechanism via which environmental risk factors could affect cells during development in individuals at risk for schizophrenia. We investigated DNA methylation in patient-derived cells that might shed light on early development in schizophrenia. Induced pluripotent stem cells may reflect a "ground state" upon which developmental and environmental influences would be minimal. Olfactory neurosphere-derived cells are an adult-derived neuro-ectodermal stem cell modified by developmental and environmental influences. Fibroblasts provide a non-neural control for life-long developmental and environmental influences. Genome-wide profiling of DNA methylation and gene expression was done in these three cell types from the same individuals. All cell types had distinct, statistically significant schizophrenia-associated differences in DNA methylation and linked gene expression, with Gene Ontology analysis showing that the differentially affected genes clustered in networks associated with cell growth, proliferation, and movement, functions known to be affected in schizophrenia patient-derived cells. Only five gene loci were differentially methylated in all three cell types. Understanding the role of epigenetics in cell function in the brain in schizophrenia is likely to be complicated by similar cell type differences in intrinsic and environmentally induced epigenetic regulation.

Genetic pathways for differentiation of the peripheral nervous system in ascidians

PubMed Central

Waki, Kana; Imai, Kaoru S.; Satou, Yutaka

2015-01-01

Ascidians belong to tunicates, the sister group of vertebrates. Peripheral nervous systems (PNSs) including epidermal sensory neurons (ESNs) in the trunk and dorsal tail regions of ascidian larvae are derived from cells adjacent to the neural plate, as in vertebrates. On the other hand, peripheral ESNs in the ventral tail region are derived from the ventral ectoderm under the control of BMP signalling, reminiscent of sensory neurons of amphioxus and protostomes. In this study, we show that two distinct mechanisms activate a common gene circuit consisting of Msx, Ascl.b, Tox, Delta.b and Pou4 in the dorsal and ventral regions to differentiate ESNs. Our results suggest that ventral ESNs of the ascidian larva are not directly homologous to vertebrate PNSs. The dorsal ESNs might have arisen via co-option of the original PNS gene circuit to the neural plate border in an ancestral chordate. PMID:26515371

The role of AIRE in human autoimmune disease.

PubMed

Akirav, Eitan M; Ruddle, Nancy H; Herold, Kevan C

2011-01-01

The autoimmune regulator (AIRE) gene encodes a transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is characterized by the clinical presentation of at least two of a triad of underlying disorders: Addison disease, hypoparathyroidism and chronic mucocutaneous candidiasis. This Review describes the process of positive and negative selection of developing T cells in the thymus and the role of AIRE as a regulator of peripheral antigen presentation. Furthermore, it addresses how mutations of this gene lead to the failure to eliminate autoreactive T cells, which can lead to clinical autoimmune syndromes.

Molecular biology and genetics of embryonic eyelid development.

PubMed

Rubinstein, Tal J; Weber, Adam C; Traboulsi, Elias I

2016-09-01

The embryology of the eyelid is a complex process that includes interactions between the surface ectoderm and mesenchymal tissues. In the mouse and human, the eyelids form and fuse before birth; they open prenatally in the human and postnatally in the mouse. In the mouse, cell migration is stimulated by different growth factors such as FGF10, TGF-α, Activin B, and HB-EGF. These growth factors modulate downstream BMP4 signaling, the ERK cascade, and JNK/c-JUN. Several mechanisms, such as the Wnt/β-catenin signaling pathway, may inhibit and regulate eyelid fusion. Eyelid opening, on the other hand, is driven by the BMP/Smad signaling system. Several human genetic disorders result from dysregulation of the above molecular pathways.

FoxA4 favours notochord formation by inhibiting contiguous mesodermal fates and restricts anterior neural development in Xenopus embryos.

PubMed

Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E; Stivala, Ernesto González; Carrasco, Andrés E; López, Silvia L

2014-01-01

In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula -chordin and -noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development.

Purification of Growth Factor mRNA in Renal Tissues:bFGF-2, FGF-2, TGFα, and EGFR.

PubMed

Mydlo, J H

2001-01-01

Growth factors are polypeptides that induce cell mitogenicity, and thus play an important role in the etiology and progression of tumors (1). Fibroblast growth factors (FGF) constitute a family of structurally related polypeptides of 146 amino acids, which exhibit a wide spectrum of biologic activities, including angiogenesis or the formation of a vascular network. FGFs are mitogenic towards many mesodermal and ectodermal cell types, and can also induce and/or inhibit differentiation of cells (2). These heparin-binding factors are categorized as FGF-1 through FGF-10. Acidic FGF, or FGF-1, is found mostly in brain and other neural tissues. Basic FGF, or FGF- 2, a protein of 18 kDa mw, is one of the most ubiqitous growth factors. It is found in numerous benign and cancerous human and animal tissues, including kidney, prostate, and bladder (3-6). In some cases it has also been demonstrated to have potential as a tumor marker (7-11). One group reported greater recovery of both FGF-2 protein and FGF-2 mRNA from renal-cancer tissue compared to equal amounts of normal renal tissue (5). Furthermore, when purified FGF-2 from renal cell carcinoma (RCC) is added exogenously to other established renal tumorcell lines and endothelial cell lines, it demonstrates significant mitogenic activity (6). Thus, renal tumors may use FGF-2 in an autocrine manner to sustain themselves.

AmphiFoxQ2, a novel winged helix/forkhead gene, exclusively marks the anterior end of the amphioxus embryo

NASA Technical Reports Server (NTRS)

Yu, Jr-Kai; Holland, Nicholas D.; Holland, Linda Z.

2003-01-01

A full-length FoxQ-related gene (AmphiFoxQ2) was isolated from amphioxus. Expression is first detectable in the animal/anterior hemisphere at the mid blastula stage. The midpoint of this expression domain coincides with the anterior pole of the embryo and is offset dorsally by about 20 degrees from the animal pole. During the gastrula stage, expression is limited to the anterior ectoderm. By the early neurula stage, expression remains in the anterior ectoderm and also appears in the adjacent anterior mesendoderm. By the early larval stages, expression is detectable in the anteriormost ectoderm and in the rostral tip of the notochord. AmphiFoxQ2 is never expressed anywhere except at the anterior tip of amphioxus embryos and larvae. This is the first gene known that exclusively marks the anterior pole of chordate embryos. It may, therefore, play an important role in establishing and/or maintaining the anterior/posterior axis.

Regulation of cell protrusions by small GTPases during fusion of the neural folds

PubMed Central

Rolo, Ana; Savery, Dawn; Escuin, Sarah; de Castro, Sandra C; Armer, Hannah EJ; Munro, Peter MG; Molè, Matteo A; Greene, Nicholas DE; Copp, Andrew J

2016-01-01

Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development. DOI: http://dx.doi.org/10.7554/eLife.13273.001 PMID:27114066

Review of ectodermal dysplasia: case report on treatment planning and surgical management of oligodontia with implant restorations.

PubMed

Li, Dehua; Liu, Yanpu; Ma, Wei; Song, Yingliang

2011-10-01

Dental implants have proven to be a reliable modality for the rehabilitation of missing teeth. However, there are limited reports on managing anodontia related to ectodermal dysplasia in the scientific literature. The severely reduced bone quantity due to the congenital absence of multiple natural teeth is the biggest challenge for the surgeon. There are a variety of bone augmentation procedures to establish adequate bone quantity, and the surgical planning should be used on an individual case basis. This is a report of a 19-year-old male patient affected by hypohidrotic ectodermal dysplasia. Oligodontia associated with severe atrophy of jaws was the chief complaint for seeking treatment. Based on clinical and radiographic examinations, 2 bone augmentation procedures were used to obtain sufficient width of alveolus for implant placement by performing an onlay bone graft in the maxilla and vertical distraction osteogenesis in the mandible. The treatment planning was discussed and informed consent was obtained.

Implant-supported Oral Rehabilitation in Child with Ectodermal Dysplasia - 4-year Follow-up.

PubMed

Cezária Triches, Thaisa; Ximenes, Marcos; Oliveira de Souza, João Gustavo; Rodrigues Lopes Pereira Neto, Armando; Cardoso, Antônio Carlos; Bolan, Michele

2017-01-01

Ectodermal dysplasia (ED) is an anomaly determined by genetic factors that alter ectodermal structures such as skin, hair, nails, glands, and teeth. Children affected by this condition require extensive, comprehensive, and multidisciplinary treatment. An 8-year-old female patient visited the Dentistry Clinic of the Federal University of Santa Catarina with the chief complaint of multiple missing teeth. The mother reported that the patient had ED. Clinical and radiographic examination revealed the congenital absence of several primary and permanent teeth and tooth germs. Subsequent oral rehabilitation comprised the application of a maxillary denture and mandibular implant-supported fixed prosthesis. The child was also supplied with a wig for further enhancement of esthetics aimed at improving her emotional wellbeing. Psychological follow-up and speech therapy were also provided. After 4 years of follow-up, implant-supported oral rehabilitation has proved to be a satisfactory treatment option, allowing restoration of masticatory, phonetic, and esthetic function, as well as an improvement in the patient's self-esteem and social wellbeing.

p63 protein is essential for the embryonic development of vibrissae and teeth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rufini, Alessandro; Weil, Miguel; McKeon, Frank

2006-02-17

Development of skin appendages strongly depends on epithelial-mesenchymal interactions. One of the genes involved in this process is p63, a member of the p53 family of transcription factors, essential for ectodermal development, as elucidated by the phenotype of p63 knock-out mice. Surprisingly, no information on p63 expression in tooth and hair is yet available. Here, we show p63 expression during teeth and vibrissae morphogenesis in mouse embryos and we also show a correlation with the expression patterns of the epithelial marker keratin 5 and the proliferation marker Ki67. Our results show that p63 colocalizes with both K5 and Ki67 inmore » the epithelium of developing vibrissae, while in teeth p63 is expressed, together with K5, in the undifferentiated ectoderm (enamel organ), and in ameloblasts, a subpopulation of differentiated ectodermal cells. Moreover, p63 expression in tooth seems not to be fully colocalized with nuclear Ki67 expression.« less

Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation.

PubMed

Plank, Jennifer L; Mundell, Nathan A; Frist, Audrey Y; LeGrone, Alison W; Kim, Thomas; Musser, Melissa A; Walter, Teagan J; Labosky, Patricia A

2011-01-15

Interactions between cells from the ectoderm and mesoderm influence development of the endodermally-derived pancreas. While much is known about how mesoderm regulates pancreatic development, relatively little is understood about how and when the ectodermally-derived neural crest regulates pancreatic development and specifically, beta cell maturation. A previous study demonstrated that signals from the neural crest regulate beta cell proliferation and ultimately, beta cell mass. Here, we expand on that work to describe timing of neural crest arrival at the developing pancreatic bud and extend our knowledge of the non-cell autonomous role for neural crest derivatives in the process of beta cell maturation. We demonstrated that murine neural crest entered the pancreatic mesenchyme between the 26 and 27 somite stages (approximately 10.0 dpc) and became intermingled with pancreatic progenitors as the epithelium branched into the surrounding mesenchyme. Using a neural crest-specific deletion of the Forkhead transcription factor Foxd3, we ablated neural crest cells that migrate to the pancreatic primordium. Consistent with previous data, in the absence of Foxd3, and therefore the absence of neural crest cells, proliferation of insulin-expressing cells and insulin-positive area are increased. Analysis of endocrine cell gene expression in the absence of neural crest demonstrated that, although the number of insulin-expressing cells was increased, beta cell maturation was significantly impaired. Decreased MafA and Pdx1 expression illustrated the defect in beta cell maturation; we discovered that without neural crest, there was a reduction in the percentage of insulin-positive cells that co-expressed Glut2 and Pdx1 compared to controls. In addition, transmission electron microscopy analyses revealed decreased numbers of characteristic insulin granules and the presence of abnormal granules in insulin-expressing cells from mutant embryos. Together, these data demonstrate that the neural crest is a critical regulator of beta cell development on two levels: by negatively regulating beta cell proliferation and by promoting beta cell maturation. Copyright © 2010 Elsevier Inc. All rights reserved.

Post-embryonic larval development and metamorphosis of the hydroid Eudendrium racemosum (Cavolini) (Hydrozoa, Cnidaria)

NASA Astrophysics Data System (ADS)

Sommer, C.

1990-09-01

The morphology and histology of the planula larva of Eudendrium racemosum (Cavolini) and its metamorphosis into the primary polyp are described from light microscopic observations. The planula hatches as a differentiated gastrula. During the lecithotrophic larval period, large ectodermal mucous cells, embedded between epitheliomuscular cells, secrete a sticky slime. Two granulated cell types occur in the ectoderm that are interpreted as secretory and sensorynervous cells, but might also be representatives of only one cell type with a multiple function. The entoderm consists of yolk-storing gastrodermal cells, digestive gland cells, interstitial cells, cnidoblasts, and premature cnidocytes. The larva starts metamorphosis by affixing its blunt aboral pole to a substratum. While the planula flattens down, the mucous cells penetrate the mesolamella and migrate through the entoderm into the gastral cavity where they are lysed. Subsequently, interstitial cells, cnidoblasts, and premature cnidocytes migrate in the opposite direction, i.e. from entoderm to ectoderm. Then, the polypoid body organization, comprising head (hydranth), stem and foot, all covered by peridermal secretion, becomes recognisable. An oral constriction divides the hypostomal portion of the gastral cavity from the stomachic portion. Within the hypostomal entoderm, cells containing secretory granules differentiate. Following growth and the multiplication of tentacles, the head periderm disappears. A ring of gland cells differentiates at the hydranth's base. The positioning of cnidae in the tentacle ectoderm, penetration of the mouth opening and the multiplication of digestive gland cells enable the polyp to change from lecithotrophic to planktotrophic nutrition.

Diagnosis of X-Linked Hypohidrotic Ectodermal Dysplasia by Meibography and Infrared Thermography of the Eye.

PubMed

Kaercher, Thomas; Dietz, Jasna; Jacobi, Christina; Berz, Reinhold; Schneider, Holm

2015-09-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical characteristics include meibomian gland disorder and the resulting hyperevaporative dry eye. In this study, we evaluated meibography and ocular infrared thermography as novel methods to diagnose XLHED. Eight infants, 12 boys and 14 male adults with XLHED and 12 healthy control subjects were subjected to a panel of tests including the ocular surface disease index (OSDI), meibography and infrared thermography, non-invasive measurement of tear film break-up time (NIBUT) and osmolarity, Schirmer's test, lissamine green staining and fluorescein staining. Sensitivity and specificity were determined for single tests and selected test combinations. Meibography had 100% sensitivity and specificity for identifying XLHED. Infrared thermography, a completely non-invasive procedure, revealed a typical pattern for male subjects with XLHED. It was, however, less sensitive (86% for adults and 67% for children) than meibography or a combination of established routine tests. In adults, OSDI and NIBUT were the best single routine tests (sensitivity of 86% and 71%, respectively), whereas increased tear osmolarity appeared as a rather unspecific ophthalmic symptom. In children, NIBUT was the most convincing routine test (sensitivity of 91%). Meibography is the most reliable ophthalmic examination to establish a clinical diagnosis in individuals with suspected hypohidrotic ectodermal dysplasia, even before genetic test results are available. Tear film tests and ocular surface staining are less sensitive in children, but very helpful for estimating the severity of ocular surface disease in individuals with known XLHED.

Ocular surface involvements in ectrodactyly-ectodermal dysplasia-cleft syndrome.

PubMed

Kennedy, David P; Chandler, John W; McCulley, James P

2015-06-01

To present the ocular manifestation of 2 cases of ectrodactyly-ectodermal dysplasia-cleft syndrome, a multiple congenital anomaly syndrome caused by a single point mutation of the p63 gene that controls epidermal development and homeostasis and to present treatment options. Patient 1 presented with mild signs and symptoms of dry eye and limbal stem cell deficiency with retention of 20/30 vision. Patient 2 presented with severe signs and symptoms of limbal stem cell deficiency with diffuse corneal scarring and counting fingers vision. This second patient's course was complicated by allergic conjunctivitis and advanced steroid-induced glaucoma. The cause of visual loss in ectrodactyly-ectodermal dysplasia-cleft syndrome appears to be multifactorial and likely includes inflammation of the ocular surface, tear film abnormalities, eyelid abnormalities, and limbal stem cell deficiency. Treatment modalities including lubrication, contact lenses, and limbal stem cell transplantation are reviewed. The ophthalmic conditions seen in ectrodactyly-ectodermal dysplasia-cleft syndrome frequently lead to vision loss. Early correct diagnosis and appropriate therapy are paramount because p63 gene mutations have a critical role in maintaining the integrity of the ocular surface in the setting of limbal stem cell deficiency, especially if there are other ocular surface insults such as lid disease, meibomian gland dysfunction and toxicity from topical medications. Patients should be monitored at regular, frequent intervals; and particular attention should be taken to avoid adverse secondary effects of these conditions and medications. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

T-Box Genes in Drosophila Mesoderm Development.

PubMed

Reim, I; Frasch, M; Schaub, C

2017-01-01

In Drosophila there are eight genes encoding transcription factors of the T-box family, which are known to exert a variety of crucial developmental functions during ectodermal patterning processes, neuronal cell specification, mesodermal tissue development, and the development of extraembryonic tissues. In this review, we focus on the prominent roles of Drosophila T-box genes in mesodermal tissues. First, we describe the contributions of brachyenteron (byn) and optomotor-blind-related-gene-1 (org-1) to the development of the visceral mesoderm. Second, we provide an overview on the functions of the three Dorsocross paralogs (Doc1-3) and the two Tbx20-related paralogs (midline and H15) during Drosophila heart development. Third, we portray the roles of org-1 and midline/H15 in the specification of individual body wall and organ-attached muscles, including the function of org-1 in the transdifferentiation of certain heart-attached muscles during metamorphosis. The functional analysis of these evolutionarily conserved T-box genes, along with their interactions with other types of transcription factors and various signaling pathways, has provided key insights into the regulation of Drosophila visceral mesoderm, muscle, and heart development. © 2017 Elsevier Inc. All rights reserved.

The Use of Human Wharton's Jelly Cells for Cochlear Tissue Engineering.

PubMed

Mellott, Adam J; Detamore, Michael S; Staecker, Hinrich

2016-01-01

Tissue engineering focuses on three primary components: stem cells, biomaterials, and growth factors. Together, the combination of these components is used to regrow and repair damaged tissues that normally do not regenerate easily on their own. Much attention has been focused on the use of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), due to their broad differentiation potential. However, ESCs and iPSCs require very detailed protocols to differentiate into target tissues, which are not always successful. Furthermore, procurement of ESCs is considered ethically controversial in some regions and procurement of iPSCs requires laborious transformation of adult tissues and characterization. However, mesenchymal stem cells are an adult stem cell population that are not ethically controversial and are readily available for procurement. Furthermore, mesenchymal stem cells exhibit the ability to differentiate into a variety of cell types arising from the mesoderm. In particular, human Wharton's jelly cells (hWJCs) are mesenchymal-type stem cells found in umbilical cords that possess remarkable differentiation potential. hWJCs are a highly desirable stem cell population due to their abundance in supply, high proliferation rates, and ability to differentiate into multiple cell types arising from all three germ layers. hWJCs are used to generate several neurological phenotypes arising from the ectoderm and are considered for engineering mechanosensory hair cells found in the auditory complex. Here, we report the methods for isolating hWJCs from human umbilical cords and non-virally transfected for use in cochlear tissue engineering studies.

High-level expression of podoplanin in benign and malignant soft tissue tumors: immunohistochemical and quantitative real-time RT-PCR analysis.

PubMed

Xu, Yongjun; Ogose, Akira; Kawashima, Hiroyuki; Hotta, Tetsuo; Ariizumi, Takashi; Li, Guidong; Umezu, Hajime; Endo, Naoto

2011-03-01

Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells. D2-40 is a commercially available mouse monoclonal antibody which binds to an epitope on human podoplanin. D2-40 immunoreactivity is therefore highly sensitive and specific for lymphatic endothelium. Recent investigations have shown widespread applications of immunohistochemical staining with D2-40 in evaluating podoplanin expression as an immunohistochemical marker for diagnosis and prognosis in various tumors. To determine whether the podoplanin (D2-40) antibody may be useful for the diagnosis of soft tissue tumors, 125 cases, including 4 kinds of benign tumors, 15 kinds of malignant tumors and 3 kinds of tumor-like lesions were immunostained using the D2-40 antibody. Total RNA was extracted from frozen tumor tissue obtained from 41 corresponding soft tissue tumor patients and 12 kinds of soft tissue tumor cell lines. Quantitative real-time PCR reactions were performed. Immunohistochemical and quantitative real-time RT-PCR analyses demonstrated the expression of the podoplanin protein and mRNA in the majority of benign and malignant soft tissue tumors and tumor-like lesions examined, with the exception of alveolar soft part sarcoma, embryonal and alveolar rhabdomyosarcoma, extraskeletal Ewing's sarcoma/peripheral primitive neuro-ectodermal tumor and lipoma, which were completely negative for podoplanin. Since it is widely and highly expressed in nearly all kinds of soft tissue tumors, especially in spindle cell sarcoma, myxoid type soft tissue tumors and soft tissue tumors of the nervous system, podoplanin is considered to have little value in the differential diagnosis of soft tissue tumors.

Systematization of ambiguous genitalia.

PubMed

Makiyan, Zograb

2016-10-01

Sex assignment in newborns depends on the anatomy of the external genitalia, despite this stage being the final in embryogenesis. According to the current view, the genital tubercle is the embryonic precursor of penis and clitoris. It originates from mesenchymal tissue, but mesenchymal cells are arranged across the embryonal body and do not have specific androgen receptors. The nature of the signal that initiates early derivation of the indifferent genital tubercle is unknown at present. The aims of this article are to improve surgical management of intersex disorders and investigate the development of the genital tubercle. Clinical examination of 114 females with various forms of DSD revealed ambiguous (bisexual) external genitalia in 73 patients, and 51 of them underwent feminizing surgery. Intersexuality (ambiguity) in 46,XY patients results from disruptors in the pathways of sex steroid hormones or receptors; in 46,XX females arises from excessive levels of androgens. Systematization of intersex disorders distinguishes the karyotype, gonadal morphology, and genital anatomy to provide a differential diagnosis and guide appropriate surgical management. Modified feminizing clitoroplasty with preservation of the dorsal and ventral neurovascular bundles to retain erogenous sensitivity was performed in females with severe virilization (Prader degree III-V). The outgrowth of the genital tubercle and the fusion of the urethral fold proceed in an ordered fashion; but in some cases of ambiguity, there was discordance due to different pathways. Speculation about the derivation of the genital tubercle have discussed with a literature review. The genital tubercle derives from the following 3 layers: the ectodermal glans of the tubercle, the mesodermal corpora cavernosa and the endodermal urogenital groove. According to the new hypothesis, during the indifferent stages, the 5 sacral somites have to recede from their segmentation and disintegrate: the sclerotomes form the pelvic bones, the fused myotomes follow with their genuine neurotomes and the angiotomes join to the corpora cavernosa of the genital tubercle. Sexual differentiation of external genitalia is final in gender embryogenesis, but surprisingly derivation of the indifferent genital tubercle from 5 somites occurs before gonadal and internal organs development.

Systematization of ambiguous genitalia

PubMed Central

Makiyan, Zograb

2016-01-01

ABSTRACT Sex assignment in newborns depends on the anatomy of the external genitalia, despite this stage being the final in embryogenesis. According to the current view, the genital tubercle is the embryonic precursor of penis and clitoris. It originates from mesenchymal tissue, but mesenchymal cells are arranged across the embryonal body and do not have specific androgen receptors. The nature of the signal that initiates early derivation of the indifferent genital tubercle is unknown at present. The aims of this article are to improve surgical management of intersex disorders and investigate the development of the genital tubercle. Clinical examination of 114 females with various forms of DSD revealed ambiguous (bisexual) external genitalia in 73 patients, and 51 of them underwent feminizing surgery. Intersexuality (ambiguity) in 46,XY patients results from disruptors in the pathways of sex steroid hormones or receptors; in 46,XX females arises from excessive levels of androgens. Systematization of intersex disorders distinguishes the karyotype, gonadal morphology, and genital anatomy to provide a differential diagnosis and guide appropriate surgical management. Modified feminizing clitoroplasty with preservation of the dorsal and ventral neurovascular bundles to retain erogenous sensitivity was performed in females with severe virilization (Prader degree III-V). The outgrowth of the genital tubercle and the fusion of the urethral fold proceed in an ordered fashion; but in some cases of ambiguity, there was discordance due to different pathways. Speculation about the derivation of the genital tubercle have discussed with a literature review. The genital tubercle derives from the following 3 layers: the ectodermal glans of the tubercle, the mesodermal corpora cavernosa and the endodermal urogenital groove. According to the new hypothesis, during the indifferent stages, the 5 sacral somites have to recede from their segmentation and disintegrate: the sclerotomes form the pelvic bones, the fused myotomes follow with their genuine neurotomes and the angiotomes join to the corpora cavernosa of the genital tubercle. Sexual differentiation of external genitalia is final in gender embryogenesis, but surprisingly derivation of the indifferent genital tubercle from 5 somites occurs before gonadal and internal organs development. PMID:27391116

Herediatary anhidrotic ectodermal dysplasia. Studies in a Nigerian famil.

PubMed Central

Familusi, J B; Jaiyesimi, F; Ojo, C O; Attah, E B

1975-01-01

Studies in a Nigerian family with hereditary anhidrous ectodermal dysplasia are reported. Microscopical examinations of finger tips for sweat pores were diagnostic in phenotypes, and it is suggested that this simple nonsurgical procedure is a preferred alternative to skin biopsies in the diagnosis of the syndrome. The clinical implications of a tropical environment for the syndrome, as well as the factors that may favour maintenance of the gene in such an environment are discussed. Images FIG. 1 FIG. 2 FIG. 4 FIG. 5 FIG. 6 PMID:1200681

Oral health considerations in a patient with oligosymptomatic ectrodactyly-ectodermal dysplasia-cleft syndrome.

PubMed

Sharma, Gaurav; Nagpal, Archna

2017-01-01

Ectrodactyly-ectodermal dysplasia-cleft (EEC) syndrome-a complex, pleiotropic disorder resulting in multiple congenital anomalies-has an unpredictable clinical expression and is typically manifested as an autosomal-dominant trait. This article presents a rare case of oligosymptomatic EEC syndrome in a 19-year-old man who exhibited atypical dental findings but no cleft lip or palate. This article is intended to create awareness about this rare syndrome and highlight the role of oral healthcare specialists in improving the quality of life for patients with EEC.

Anhidrotic ectodermal dysplasia gene region cloned in yeast artificial chromosomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kere, J.; Grzeschik, K.H.; Limon, J.

1993-05-01

Anhidrotic ectodermal dysplasia (EDA), an X-chromosomal recessive disorder, is expressed in a few females with chromosomal translocations involving bands Xq12-q13. Using available DNA markers from the region and somatic cell hybrids the authors mapped the X-chromosomal breakpoints in two such translocations. The breakpoints were further mapped within a yeast artificial chromosome contig constructed by chromosome walking techniques. Genomic DNA markers that map between the two translocation breakpoints were recovered representing putative portions of the EDA gene. 32 refs., 3 figs., 1 tab.

Plakophilin-1, a Novel Wnt Signaling Regulator, Is Critical for Tooth Development and Ameloblast Differentiation

PubMed Central

Arai, Chieko; Yamada, Aya; Saito, Kan; Ishikawa, Masaki; Xue, Han; Funada, Keita; Haruyama, Naoto; Yamada, Yoshihiko; Fukumoto, Satoshi; Takahashi, Ichiro

2016-01-01

Tooth morphogenesis is initiated by reciprocal interactions between the ectoderm and neural crest-derived mesenchyme, and the Wnt signaling pathway is involved in this process. We found that Plakophilin (PKP)1, which is associated with diseases such as ectodermal dysplasia/skin fragility syndrome, was highly expressed in teeth and skin, and was upregulated during tooth development. We hypothesized that PKP1 regulates Wnt signaling via its armadillo repeat domain in a manner similar to β-catenin. To determine its role in tooth development, we performed Pkp1 knockdown experiments using ex vivo organ cultures and cell cultures. Loss of Pkp1 reduced the size of tooth germs and inhibited dental epithelial cell proliferation, which was stimulated by Wnt3a. Furthermore, transfected PKP1-emerald green fluorescent protein was translocated from the plasma membrane to the nucleus upon stimulation with Wnt3a and LiCl, which required the PKP1 N terminus (amino acids 161 to 270). Localization of PKP1, which is known as an adhesion-related desmosome component, shifted to the plasma membrane during ameloblast differentiation. In addition, Pkp1 knockdown disrupted the localization of Zona occludens 1 in tight junctions and inhibited ameloblast differentiation; the two proteins were shown to directly interact by immunoprecipitation. These results implicate the participation of PKP1 in early tooth morphogenesis as an effector of canonical Wnt signaling that controls ameloblast differentiation via regulation of the cell adhesion complex. PMID:27015268

Chordate betagamma-crystallins and the evolutionary developmental biology of the vertebrate lens.

PubMed

Riyahi, Kumars; Shimeld, Sebastian M

2007-07-01

Several animal lineages, including the vertebrates, have evolved sophisticated eyes with lenses that refract light to generate an image. The nearest invertebrate relatives of the vertebrates, such as the ascidians (sea squirts) and amphioxus, have only basic light detecting organs, leading to the widely-held view that the vertebrate lens is an innovation that evolved in early vertebrates. From an embryological perspective the lens is different from the rest of the eye, in that the eye is primarily of neural origin while the lens derives from a non-neural ectodermal placode which invaginates into the developing eye. How such an organ could have evolved has attracted much speculation. Recently, however, molecular developmental studies of sea squirts have started to suggest a possible evolutionary origin for the lens. First, studies of the Pax, Six, Eya and other gene families have indicated that sea squirts have areas of non-neural ectoderm homologous to placodes, suggesting an origin for the embryological characteristics of the lens. Second, the evolution and regulation of the betagamma-crystallins has been studied. These form one of the key crystallin gene families responsible for the transparency of the lens, and regulatory conservation between the betagamma-crystallin gene in the sea squirt Ciona intestinalis and the vertebrate visual system has been experimentally demonstrated. These data, together with knowledge of the morphological, physiological and gene expression similarities between the C. intestinalis ocellus and vertebrate retina, have led us to propose a hypothesis for the evolution of the vertebrate lens and integrated vertebrate eye via the co-option and combination of ancient gene regulatory networks; one controlling morphogenetic aspects of lens development and one controlling the expression of a gene family responsible for the biophysical properties of the lens, with the components of the retina having evolved from an ancestral photoreceptive organ derived from the anterior central nervous system.

Generation of tooth-periodontium complex structures using high-odontogenic potential dental epithelium derived from mouse embryonic stem cells.

PubMed

Zhang, Yancong; Li, Yongliang; Shi, Ruirui; Zhang, Siqi; Liu, Hao; Zheng, Yunfei; Li, Yan; Cai, Jinglei; Pei, Duanqing; Wei, Shicheng

2017-06-08

A number of studies have shown that tooth-like structures can be regenerated using induced pluripotent stem cells and mouse embryonic stem (mES) cells. However, few studies have reported the regeneration of tooth-periodontium complex structures, which are more suitable for clinical tooth transplantation. We established an optimized approach to induce high-odontogenic potential dental epithelium derived from mES cells by temporally controlling bone morphogenic protein 4 (BMP4) function and regenerated tooth-periodontium complex structures in vivo. First, immunofluorescence and quantitative reverse transcription-polymerase chain reaction were used to identify the watershed of skin and the oral ectoderm. LDN193189 was then used to inhibit the BMP4 receptor around the watershed, followed by the addition of exogenous BMP4 to promote BMP4 function. The generated dental epithelium was confirmed by western blot analysis and immunofluorescence. The generated epithelium was ultimately combined with embryonic day 14.5 mouse mesenchyme and transplanted into the renal capsules of nude mice. After 4 weeks, the tooth-periodontium complex structure was examined by micro-computed tomography (CT) and hematoxylin and eosin (H&E) staining. Our study found that the turning point of oral ectoderm differentiation occurred around day 3 after the embryoid body was transferred to a common culture plate. Ameloblastin-positive dental epithelial cells were detected following the temporal regulation of BMP4. Tooth-periodontium complex structures, which included teeth, a periodontal membrane, and alveolar bone, were formed when this epithelium was combined with mouse dental mesenchyme and transplanted into the renal capsules of nude mice. Micro-CT and H&E staining revealed that the generated tooth-periodontium complex structures shared a similar histological structure with normal mouse teeth. An optimized induction method was established to promote the differentiation of mES cells into dental epithelium by temporally controlling the function of BMP4. A novel tooth-periodontium complex structure was generated using the epithelium.

Single cell cultures of Drosophila neuroectodermal and mesectodermal central nervous system progenitors reveal different degrees of developmental autonomy.

PubMed

Lüer, Karin; Technau, Gerhard M

2009-08-03

The Drosophila embryonic central nervous system (CNS) develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in the embryo. However, presumptive neuroblasts, once specified in the neuroectoderm, exhibit a higher degree of autonomy regarding generation of their lineages compared to mesectodermal midline progenitors.

Gene p63: In ectrodactyly-ectodermal dysplasia clefting, ankyloblepharon-ectodermal dysplasia, Rapp-Hodgkin syndrome.

PubMed

van Straten, Cornelia; Butow, Kurt-W

2013-01-01

An analysis was made of three different syndromes associated with p63 gene mutations, known as ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC), ankyloblepharon-ectodermal dysplasia clefting syndrome (AEC or Hay-Wells) and Rapp-Hodgkin syndrome (RHS). The postoperative complications associated with their cleft reconstructions were also evaluated. Extensive demographic information, in particular of the clinical appearances, associated malformations, and the types and complications of the reconstructive surgical procedures, were recorded of these syndromic cases occurring in a database of 3621 facial cleft deformity patients. The data was analyzed using the Microsoft Excel program. A total of 10 (0.28%) cases of p63 associated syndromes were recorded: EEC (6), RHS (3), and AEC (1). The following clinical cleft appearances were noted - EEC = 6: CLA 1 -right side unilateral (female); CLAP 4 - right side (1) + left side (1) unilateral (male + female); bilateral (2) (males); hPsP 1 (female) (divided in 3 Black, 2 White, 1 Indian); RHS = 3: CLAP 2 (White males); hPsP 1 (White female); AEC = 1: CLAP bilateral (White male). Other features of the syndromes were: skin, hand, foot, tooth, hair and nail involvement, and light sensitivity. Postoperative complications included: (i) stenosis of nasal opening, especially after reconstruction of the bilateral cleft lip and the columella lengthening (2 cases), (ii) premaxilla-prolabium fusion (2 cases), (iii) repeated occurrence of oro-nasal fistula in the hard palate (4 cases), and (iv) dysgnathial development of midfacial structures (3 cases). Three different p63 associated syndromes (EEC, AEC, and RHS) were diagnosed (0.27% of the total facial cleft deformities database). The majority of the cases presented with a bilateral CLAP in males only. A number of females and males had unilateral CLA. The hPsP-cleft was recorded in females only. The associated ectodermal component most probably had a profoundly negative influence on postoperatively wound healing, which was observed in particular at the nasal openings, the premaxilla sulcus and in the hard palate mucosa. The reconstruction of p63 associated syndromes is a greater challenge than the usual cleft reconstruction to the surgeon.

An RGDS peptide-binding receptor, FR-1R, localizes to the basal side of the ectoderm and to primary mesenchyme cells in sand dollar embryos.

PubMed

Katow, H; Sofuku, S

2001-10-01

Immunoblotting using polyclonal antibodies (pAb) raised against an FR-1 receptor (FR-1R), a 57 kDa Arg-Gly-Asp-Ser (RGDS)-binding protein, of the sand dollar Clypeaster japonicus showed that the pAb monospecifically bound to the protein. FR-1R was present in purified plasma membrane, suggesting that the protein is a membrane-bound protein. The molecular structure of FR-1R did not change throughout the early embryogenesis, whereas its expression changed significantly during this period. FR-1R was present in the cortex of unfertilized eggs and was then transferred to the hyaline layer soon after the fertilization. The hyaline layer retained FR-1R immunoreactivity during early embryogenesis. FR-1R appeared on the basal side of the ectoderm at the morula stage and was retained basolaterally, at least, to the early gastrula stage. In mesenchyme blastulae, FR-1R was also present on the surface of primary mesenchyme cells (PMC). FR-1R was localized on the basal side of the ectoderm in early gastrulae, exclusively at the place where PMC formed ventrolateral aggregates, and at the apical tuft ectoderm. In vitro, PMC bound to FR-1R and its binding was inhibited in the presence of a synthetic RGDS peptide or the pAb. The pAb introduced into the blastocoele perturbed PMC migration and gastrulation. FR-1R was weakly recognized by antihuman integrin beta5 subunit pAb.

Karyotyping, dermatoglyphic, and sweat pore analysis of five families affected with ectodermal dysplasia

PubMed Central

Sidhu, Manpreet; Kale, Alka D; Kotrashetti, Vijayalakshmi S

2012-01-01

Background: Hereditary ectodermal dysplasia is a genetic recessive trait characterized by hypohydrosis, hypotrichosis, and hypodontia. The affected individual show characteristic physiognomy like protruded forehead, depressed nasal bridge, periorbital wrinkling, protruded lips, etc. There is marked decrease in sweat and salivary secretion. Due to skin involvement palm and sole ridge patterns are disrupted. Aim: In this study an attempt has been made to classify the affected members according to the degree of penetrance by pedigree analysis and also study karyotyping for cytogenetics, dermatoglyphic analysis for the various ridge patterns and variations in the number of sweat glands by sweat pore analysis in affected individuals. Materials and Methods: A total of five families who were affected with ectodermal dysplasia were considered. Pedigree analysis was drawn up to three generation by obtaining history. Dermatoglyphics and sweat pore analysis was done by obtaining palm and finger print impression using stamp pad ink. Karyotyping was done by collecting 3–5 ml peripheral blood. Karyotyping was prepared using lymphocyte culture. Chromosomes were examined at 20 spreads selected randomly under ×100 magnification. Results were analyzed by calculating mean values and percentage was obtained. Results: Karyotyping did not show any abnormalities, dermatoglyphic analysis and sweat pore counts showed marked variations when compared with normal. Moreover, pedigree analysis confirmed the status of the disease as that of the recessive trait. Conclusion: Large number of affected patients needs to be evaluated for dermatoglypic analysis. Genetic aspect of the disease needs to be looked into the molecular level in an attempt to locate the gene locus responsible for ectodermal dysplasia and its manifestation. PMID:23248471

Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

PubMed

Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

2015-10-01

NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. Copyright © 2015 Elsevier Inc. All rights reserved.

Branching out: origins of the sea urchin larval skeleton in development and evolution

PubMed Central

McIntyre, Daniel C.; Lyons, Deirdre C.; Martik, Megan; McClay, David R.

2014-01-01

It is a challenge to understand how the information encoded in DNA is used to build a three dimensional structure. To explore how this works the assembly of a relatively simple skeleton has been examined at multiple control levels. The skeleton of the sea urchin embryo consists of a number of calcite rods produced by 64 skeletogenic cells. The ectoderm supplies spatial cues for patterning, essentially telling the skeletogenic cells where to position themselves and providing the factors for skeletal growth. Here we describe the information known about how this works. First the ectoderm must be patterned so that the signaling cues are released from precise positions. The skeletogenic cells respond by initiating skeletogenesis immediately beneath two regions (one on the right and the other on the left side). Growth of the skeletal rods requires additional signaling from defined ectodermal locations, and the skeletogenic cells respond to produce a membrane-bound template in which the calcite crystal grows. Important in this process are three signals, FGF, VEGF, and Wnt5. Each is necessary for explicit tasks in skeleton production. PMID:24549853

Tissue-tissue interaction-triggered calcium elevation is required for cell polarization during Xenopus gastrulation.

PubMed

Shindo, Asako; Hara, Yusuke; Yamamoto, Takamasa S; Ohkura, Masamichi; Nakai, Junichi; Ueno, Naoto

2010-02-02

The establishment of cell polarity is crucial for embryonic cells to acquire their proper morphologies and functions, because cell alignment and intracellular events are coordinated in tissues during embryogenesis according to the cell polarity. Although much is known about the molecules involved in cell polarization, the direct trigger of the process remains largely obscure. We previously demonstrated that the tissue boundary between the chordamesoderm and lateral mesoderm of Xenopus laevis is important for chordamesodermal cell polarity. Here, we examined the intracellular calcium dynamics during boundary formation between two different tissues. In a combination culture of nodal-induced chordamesodermal explants and a heterogeneous tissue, such as ectoderm or lateral mesoderm, the chordamesodermal cells near the boundary frequently displayed intracellular calcium elevation; this frequency was significantly less when homogeneous explants were used. Inhibition of the intracellular calcium elevation blocked cell polarization in the chordamesodermal explants. We also observed frequent calcium waves near the boundary of the dorsal marginal zone (DMZ) dissected from an early gastrula-stage embryo. Optical sectioning revealed that where heterogeneous explants touched, the chordamesodermal surface formed a wedge with the narrow end tucked under the heterogeneous explant. No such configuration was seen between homogeneous explants. When physical force was exerted against a chordamesodermal explant with a glass needle at an angle similar to that created in the explant, or migrating chordamesodermal cells crawled beneath a silicone block, intracellular calcium elevation was frequent and cell polarization was induced. Finally, we demonstrated that a purinergic receptor, which is implicated in mechano-sensing, is required for such frequent calcium elevation in chordamesoderm and for cell polarization. This study raises the possibility that tissue-tissue interaction generates mechanical forces through cell-cell contact that initiates coordinated cell polarization through a transient increase in intracellular calcium.

Neural tube programming and craniofacial cleft formation. I. The neuromeric organization of the head and neck.

PubMed

Carstens, Michael H

2004-01-01

This review presents a brief synopsis of neuromeric theory. Neuromeres are developmental units of the nervous system with specific anatomic content. Outlying each neuromere are tissues of ectoderm, mesoderm and endoderm that bear an anatomic relationship to the neuromere in three basic ways. This relationship is physical in that motor and sensory connections exist between a given neuromeric level and its target tissues. The relationship is also developmental because the target cells exit during gastrulation precisely at that same level. Finally the relationship is chemical because the genetic definition of a neuromere is shared with those tissues with which it interacts. The model developed by Puelles and Rubenstein is used to describe the neuroanatomy of the neuromeres. Although important details of the model are currently being refined it has immediate clinical relevance for practicing clinicians because it permits us to understand many pathologic states as relationships between the brain and the surrounding tissues. Relationships between the processes of neurulation and gastrulation have been presented to demonstrate the manner in which neuromeric anatomy is established in the embryo. We are now in a position to describe in detail the static anatomic structures that result from this system. The neuromeric 'map' of craniofacial bones, dermis, dura, muscles, and fascia will be the subject of the next part of this series.

A distinct type of hidrotic ectodermal dysplasia.

PubMed

Halal, F; Setton, N; Wang, N S

1991-03-15

Four individuals from 2 generations of a family had a hidrotic type of ectodermal dysplasia (ED). Males and females were similarly affected. They had trichodysplasia, with absent eyebrows and eyelashes; normal teeth, onychodysplasia; normal sweating; mild retrognathia; abnormal dermatoglyphics; and mental retardation. Additional variable manifestations included irregular menses, high implanted or prominent ears, café-au-lait spot, keratosis pilaris, supernumerary nipple, and mild hearing loss. Their previously undescribed condition could be classified as an ED of 1-3 (trichoonychial) subgroup of group A according to Freire-Maia's classification and is inherited as an autosomal recessive trait.

Chordate evolution and the origin of craniates: an old brain in a new head.

PubMed

Butler, A B

2000-06-15

The earliest craniates achieved a unique condition among bilaterally symmetrical animals: they possessed enlarged, elaborated brains with paired sense organs and unique derivatives of neural crest and placodal tissues, including peripheral sensory ganglia, visceral arches, and head skeleton. The craniate sister taxon, cephalochordates, has rostral portions of the neuraxis that are homologous to some of the major divisions of craniate brains. Moreover, recent data indicate that many genes involved in patterning the nervous system are common to all bilaterally symmetrical animals and have been inherited from a common ancestor. Craniates, thus, have an "old" brain in a new head, due to re-expression of these anciently acquired genes. The transition to the craniate brain from a cephalochordate-like ancestral form may have involved a mediolateral shift in expression of the genes that specify nervous system development from various parts of the ectoderm. It is suggested here that the transition was sequential. The first step involved the presence of paired, lateral eyes, elaboration of the alar plate, and enhancement of the descending visual pathway to brainstem motor centers. Subsequently, this central visual pathway served as a template for the additional sensory systems that were elaborated and/or augmented with the "bloom" of migratory neural crest and placodes. This model accounts for the marked uniformity of pattern across central sensory pathways and for the lack of any neural crest-placode cranial nerve for either the diencephalon or mesencephalon. Anat Rec (New Anat) 261:111-125, 2000. Copyright 2000 Wiley-Liss, Inc.

Modelling human disease with pluripotent stem cells.

PubMed

Siller, Richard; Greenhough, Sebastian; Park, In-Hyun; Sullivan, Gareth J

2013-04-01

Recent progress in the field of cellular reprogramming has opened up the doors to a new era of disease modelling, as pluripotent stem cells representing a myriad of genetic diseases can now be produced from patient tissue. These cells can be expanded and differentiated to produce a potentially limitless supply of the affected cell type, which can then be used as a tool to improve understanding of disease mechanisms and test therapeutic interventions. This process requires high levels of scrutiny and validation at every stage, but international standards for the characterisation of pluripotent cells and their progeny have yet to be established. Here we discuss the current state of the art with regard to modelling diseases affecting the ectodermal, mesodermal and endodermal lineages, focussing on studies which have demonstrated a disease phenotype in the tissue of interest. We also discuss the utility of pluripotent cell technology for the modelling of cancer and infectious disease. Finally, we spell out the technical and scientific challenges which must be addressed if the field is to deliver on its potential and produce improved patient outcomes in the clinic.

A soma-to-germline transformation in long-lived C. elegans mutants

PubMed Central

Curran, Sean P.; Wu, Xiaoyun; Riedel, Christian G.; Ruvkun, Gary

2009-01-01

Unlike the soma which ages during the lifespan of multicellular organisms, the germline traces an essentially immortal lineage. Genomic instability in somatic cells increases with age, and this decline in somatic maintenance might be regulated to facilitate resource reallocation toward reproduction at the expense of cellular senescence. We report here that C. elegans mutants with increased longevity exhibit a soma-to-germline transformation of gene expression programs normally limited to the germline. Decreased insulin-like signaling causes the somatic misexpression of germline-limited pie-1 and pgl family of genes in intestinal and ectodermal tissues. DAF-16/FoxO, the major transcriptional effector of insulin-like signaling, regulates pie-1 expression by directly binding to the pie-1 promoter. The somatic tissues of insulin-like mutants are more germline-like and protected from genotoxic stress. Gene inactivation of components of the cytosolic chaperonin complex that induce increased longevity also cause somatic misexpression of PGL-1. These results suggest that the acquisition of germline characteristics by the somatic cells of C. elegans mutants with increased longevity contributes to their increased health and survival. PMID:19506556

Lateral adhesion drives reintegration of misplaced cells into epithelial monolayers

PubMed Central

St Johnston, Daniel

2016-01-01

Cells in simple epithelia orient their mitotic spindles in the plane of the epithelium so that both daughter cells are born within the epithelial sheet. This is assumed to be important to maintain epithelial integrity and prevent hyperplasia, because misaligned divisions give rise to cells outside the epithelium1,2. Here we test this assumption in three types of Drosophila epithelia; the cuboidal follicle epithelium, the columnar early embryonic ectoderm, and the pseudostratified neuroepithelium. Ectopic expression of Inscuteable in these tissues reorients mitotic spindles, resulting in one daughter cell being born outside of the epithelial layer. Live imaging reveals that these misplaced cells reintegrate into the tissue. Reducing the levels of the lateral homophilic adhesion molecules Neuroglian or Fasciclin 2 disrupts reintegration, giving rise to extra-epithelial cells, whereas disruption of adherens junctions has no effect. Thus, the reinsertion of misplaced cells appears to be driven by lateral adhesion, which pulls cells born outside the epithelia layer back into it. Our findings reveal a robust mechanism that protects epithelia against the consequences of misoriented divisions. PMID:26414404

Regeneration of bone and periodontal ligament induced by recombinant amelogenin after periodontitis.

PubMed

Haze, Amir; Taylor, Angela L; Haegewald, Stefan; Leiser, Yoav; Shay, Boaz; Rosenfeld, Eli; Gruenbaum-Cohen, Yael; Dafni, Leah; Zimmermann, Bernd; Heikinheimo, Kristiina; Gibson, Carolyn W; Fisher, Larry W; Young, Marian F; Blumenfeld, Anat; Bernimoulin, Jean P; Deutsch, Dan

2009-06-01

Regeneration of mineralized tissues affected by chronic diseases comprises a major scientific and clinical challenge. Periodontitis, one such prevalent disease, involves destruction of the tooth-supporting tissues, alveolar bone, periodontal-ligament and cementum, often leading to tooth loss. In 1997, it became clear that, in addition to their function in enamel formation, the hydrophobic ectodermal enamel matrix proteins (EMPs) play a role in the regeneration of these periodontal tissues. The epithelial EMPs are a heterogeneous mixture of polypeptides encoded by several genes. It was not clear, however, which of these many EMPs induces the regeneration and what mechanisms are involved. Here we show that a single recombinant human amelogenin protein (rHAM(+)), induced in vivo regeneration of all tooth-supporting tissues after creation of experimental periodontitis in a dog model. To further understand the regeneration process, amelogenin expression was detected in normal and regenerating cells of the alveolar bone (osteocytes, osteoblasts and osteoclasts), periodontal ligament, cementum and in bone marrow stromal cells. Amelogenin expression was highest in areas of high bone turnover and activity. Further studies showed that during the first 2 weeks after application, rHAM(+) induced, directly or indirectly, significant recruitment of mesenchymal progenitor cells, which later differentiated to form the regenerated periodontal tissues. The ability of a single protein to bring about regeneration of all periodontal tissues, in the correct spatio-temporal order, through recruitment of mesenchymal progenitor cells, could pave the way for development of new therapeutic devices for treatment of periodontal, bone and ligament diseases based on rHAM(+).

PSA-NCAM-Negative Neural Crest Cells Emerging during Neural Induction of Pluripotent Stem Cells Cause Mesodermal Tumors and Unwanted Grafts

PubMed Central

Lee, Dongjin R.; Yoo, Jeong-Eun; Lee, Jae Souk; Park, Sanghyun; Lee, Junwon; Park, Chul-Yong; Ji, Eunhyun; Kim, Han-Soo; Hwang, Dong-Youn; Kim, Dae-Sung; Kim, Dong-Wook

2015-01-01

Summary Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)− cells among the early NPCs caused tumors, whereas PSA-NCAM+ cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM− cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM− cells in a gradient manner mixed with PSA-NCAM+ cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN+ cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM− cells eliminates the tumorigenic potential originating from NCSCs after transplantation. PMID:25937368

The molecular basis of neurosensory cell formation in ear development: a blueprint for hair cell and sensory neuron regeneration?

PubMed Central

Fritzsch, Bernd; Beisel, Kirk W.; Hansen, Laura

2014-01-01

Summary The inner ear of mammals uses neurosensory cells derived from the embryonic ear for mechanoelectric transduction of vestibular and auditory stimuli (the hair cells) and conducts this information to the brain via sensory neurons. As with most other neurons of mammals, lost hair cells and sensory neurons are not spontaneously replaced and result instead in age-dependent progressive hearing loss. We review the molecular basis of neurosensory development in the mouse ear to provide a blueprint for possible enhancement of therapeutically useful transformation of stem cells into lost neurosensory cells. We identify several readily available adult sources of stem cells that express, like the ectoderm-derived ear, genes known to be essential for ear development. Use of these stem cells combined with molecular insights into neurosensory cell specification and proliferation regulation of the ear, might allow for neurosensory regeneration of mammalian ears in the near future. PMID:17120192

Autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency caused by a novel NFKBIA mutation, p.Ser36Tyr, presents with mild ectodermal dysplasia and non-infectious systemic inflammation.

PubMed

Yoshioka, Takakazu; Nishikomori, Ryuta; Hara, Junichi; Okada, Keiko; Hashii, Yoshiko; Okafuji, Ikuo; Nodomi, Seishiro; Kawai, Tomoki; Izawa, Kazushi; Ohnishi, Hidenori; Yasumi, Takahiro; Nakahata, Tatsutoshi; Heike, Toshio

2013-10-01

Anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) is characterized by hypohidrosis, dental abnormalities, sparse hair, and immunodeficiency. Autosomal dominant (AD)-EDA-ID, caused by a heterozygous mutation within NFKBIA, is very rare and its clinical features remain largely unknown. This study describes a patient with AD-EDA-ID harboring a novel NFKBIA mutation who presented with mild EDA and non-infectious systemic inflammation. The clinical presentation of an AD-EDA-ID patient was described and immunological, genetic, and biochemical analyses were performed, with a focus on nuclear factor kappa B (NF-κB) activation. The patient presented with symptoms of mild EDA-ID, namely sparse hair and hypohidrosis, although a skin biopsy confirmed the presence of sweat glands. There were no dental abnormalities. The patient also suffered from non-infectious inflammation, which responded to systemic corticosteroid therapy; however, the patient remained ill. Immunological analyses revealed reduced Toll-like receptor/IL-1 (TLR/IL-1) and tumor necrosis factor (TNF) receptor family responses to various stimuli. Genetic analysis identified a de novo heterozygous missense mutation, p.Ser36Tyr, in NFKBIA, resulting in defective NFKBIA degradation and impaired NF-κB activation. The patient was diagnosed with AD-EDA-ID and underwent hematopoietic stem cell transplantation. Engraftment was successful, with few signs of acute graft versus host disease. However, the patient suffered hemolytic anemia and thrombocytopenia, and died from a brain hemorrhage due to intractable thrombocytopenia. AD-EDA-ID patients can present with mild ectodermal dysplasia and non-infectious inflammation, rather than with recurrent infections. Also, hematopoietic stem cell transplantation for AD-EDA-ID is still a clinical challenge.

Gli3-mediated somitic Fgf10 expression gradients are required for the induction and patterning of mammary epithelium along the embryonic axes.

PubMed

Veltmaat, Jacqueline M; Relaix, Frédéric; Le, Lendy T; Kratochwil, Klaus; Sala, Frédéric G; van Veelen, Wendy; Rice, Ritva; Spencer-Dene, Bradley; Mailleux, Arnaud A; Rice, David P; Thiery, Jean Paul; Bellusci, Saverio

2006-06-01

Little is known about the regulation of cell fate decisions that lead to the formation of five pairs of mammary placodes in the surface ectoderm of the mouse embryo. We have previously shown that fibroblast growth factor 10 (FGF10) is required for the formation of mammary placodes 1, 2, 3 and 5. Here, we have found that Fgf10 is expressed only in the somites underlying placodes 2 and 3, in gradients across and within these somites. To test whether somitic FGF10 is required for the formation of these two placodes, we analyzed a number of mutants with different perturbations of somitic Fgf10 gradients for the presence of WNT signals and ectodermal multilayering, markers for mammary line and placode formation. The mammary line is displaced dorsally, and formation of placode 3 is impaired in Pax3ILZ/ILZ mutants, which do not form ventral somitic buds. Mammary line formation is impaired and placode 3 is absent in Gli3Xt-J/Xt-J and hypomorphic Fgf10 mutants, in which the somitic Fgf10 gradient is shortened dorsally and less overall Fgf10 is expressed, respectively. Recombinant FGF10 rescued mammogenesis in Fgf10(-/-) and Gli3Xt-J/Xt-J flanks. We correlate increasing levels of somitic FGF10 with progressive maturation of the surface ectoderm, and show that full expression of somitic Fgf10, co-regulated by GLI3, is required for the anteroposterior pattern in which the flank ectoderm acquires a mammary epithelial identity. We propose that the intra-somitic Fgf10 gradient, together with ventral elongation of the somites, determines the correct dorsoventral position of mammary epithelium along the flank.

The lateral mesodermal divide: an epigenetic model of the origin of paired fins.

PubMed

Nuño de la Rosa, Laura; Müller, Gerd B; Metscher, Brian D

2014-01-01

By examining development at the level of tissues and processes, rather than focusing on gene expression, we have formulated a general hypothesis to explain the dorso-ventral and anterior-posterior placement of paired appendage initiation sites in vertebrates. According to our model, the number and position of paired appendages are due to a commonality of embryonic tissue environments determined by the global interactions involving the two separated layers (somatic and visceral) of lateral plate mesoderm along the dorso-ventral and anterior-posterior axes of the embryo. We identify this distribution of developmental conditions, as modulated by the separation/contact of the two LPM layers and their interactions with somitic mesoderm, ectoderm, and endoderm as a dynamic developmental entity which we have termed the lateral mesodermal divide (LMD). Where the divide results in a certain tissue environment, fin bud initiation can occur. According to our hypothesis, the influence of the developing gut suppresses limb initiation along the midgut region and the ventral body wall owing to an "endodermal predominance." From an evolutionary perspective, the lack of gut regionalization in agnathans reflects the ancestral absence of these conditions, and the elaboration of the gut together with the concomitant changes to the LMD in the gnathostomes could have led to the origin of paired fins. © 2013 Wiley Periodicals, Inc.

Life Cycle Reversal in Aurelia sp.1 (Cnidaria, Scyphozoa)

PubMed Central

He, Jinru; Zheng, Lianming; Zhang, Wenjing; Lin, Yuanshao

2015-01-01

The genus Aurelia is one of the major contributors to jellyfish blooms in coastal waters, possibly due in part to hydroclimatic and anthropogenic causes, as well as their highly adaptive reproductive traits. Despite the wide plasticity of cnidarian life cycles, especially those recognized in certain Hydroza species, the known modifications of Aurelia life history were mostly restricted to its polyp stage. In this study, we document the formation of polyps directly from the ectoderm of degenerating juvenile medusae, cell masses from medusa tissue fragments, and subumbrella of living medusae. This is the first evidence for back-transformation of sexually mature medusae into polyps in Aurelia sp.1. The resulting reconstruction of the schematic life cycle of Aurelia reveals the underestimated potential of life cycle reversal in scyphozoan medusae, with possible implications for biological and ecological studies. PMID:26690755

The peripheral sensory nervous system in the vertebrate head: a gene regulatory perspective.

PubMed

Grocott, Timothy; Tambalo, Monica; Streit, Andrea

2012-10-01

In the vertebrate head, crucial parts of the sense organs and sensory ganglia develop from special regions, the cranial placodes. Despite their cellular and functional diversity, they arise from a common field of multipotent progenitors and acquire distinct identity later under the influence of local signalling. Here we present the gene regulatory network that summarises our current understanding of how sensory cells are specified, how they become different from other ectodermal derivatives and how they begin to diversify to generate placodes with different identities. This analysis reveals how sequential activation of sets of transcription factors subdivides the ectoderm over time into smaller domains of progenitors for the central nervous system, neural crest, epidermis and sensory placodes. Within this hierarchy the timing of signalling and developmental history of each cell population is of critical importance to determine the ultimate outcome. A reoccurring theme is that local signals set up broad gene expression domains, which are further refined by mutual repression between different transcription factors. The Six and Eya network lies at the heart of sensory progenitor specification. In a positive feedback loop these factors perpetuate their own expression thus stabilising pre-placodal fate, while simultaneously repressing neural and neural crest specific factors. Downstream of the Six and Eya cassette, Pax genes in combination with other factors begin to impart regional identity to placode progenitors. While our review highlights the wealth of information available, it also points to the lack information on the cis-regulatory mechanisms that control placode specification and of how the repeated use of signalling input is integrated. Copyright © 2012. Published by Elsevier Inc.

Cleft palate and ADULT phenotype in a patient with a novel TP63 mutation suggests lumping of EEC/LM/ADULT syndromes into a unique entity: ELA syndrome.

PubMed

Prontera, Paolo; Garelli, Emanuela; Isidori, Ilenia; Mencarelli, Amedea; Carando, Adriana; Silengo, Margherita Cirillo; Donti, Emilio

2011-11-01

Acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome is a rare condition belonging to the group of ectodermal dysplasias caused by TP63 mutations. Its clinical phenotype is similar to ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) and limb-mammary syndrome (LMS), and differs from these disorders mainly by the absence of cleft lip and/or palate. We report on a 39-year-old patient who was found to be heterozygous for a c.401G > T (p.Gly134Val) de novo mutation of TP63. This patient had the ADULT phenotype associated with cleft palate. Our findings, rather than extend the clinical spectrum of ADULT syndrome, suggest that cleft palate can no longer be considered an element for differential diagnosis for ADULT, EEC, and LMS. Our data, added to other reports on overlapping phenotypes, support the combining of these three phenotypes into a unique entity that we propose to call "ELA syndrome," which is an acronym of ectrodactyly-ectodermal dysplasia-cleft lip and palate, limb-mammary, and ADULT syndromes. Copyright © 2011 Wiley Periodicals, Inc.

The origin of mesoderm in phoronids

NASA Technical Reports Server (NTRS)

Freeman, Gary; Martindale, Mark Q.

2002-01-01

Descriptive studies of phoronid development have concluded that the mesoderm of these animals originates from the endoderm during gastrulation. This interpretation has been tested by labeling one blastomere of 4- through 16-cell embryos and examining the position and germ layers occupied by the labeled clones of cells in the larva. No 2 injections gave rise to identical clones of cells, suggesting that the cleavage program does not generate cells of unique identity and that cell fates are established at later developmental time points. In many cases, a relatively large sector composed of ectodermal cells was labeled. When these labeled cells were adjacent to the mouth or anus of the larva, muscle and mesenchyme cells originated from the labeled clones. Under these circumstances, nerve cells also originated from these labeled sectors. These labeling studies also showed that endodermal cells can give rise to mesodermal and neural cells. These results suggest that nerve and muscle cells are induced to form at ectodermal-endodermal boundaries from both germ layers. These marking experiments also confirmed the observation that nerve cells originate both from the apical organ and the trunk region and show for the first time that the intestine originates by ingression of posterior ectoderm.

The two nerve rings of the hypostomal nervous system of Hydra vulgaris-an immunohistochemical analysis.

PubMed

Hufnagel, L A; Kass-Simon, G

2016-11-01

In Hydra vulgaris, physiological and pharmacological evidence exists for a hypostomal circumferential neuro-effector pathway that initiates ectodermal pacemaker activity at tentacular-hypostomal loci coordinating body and tentacle contractions. Here, we describe an ectodermal nerve ring that runs below and between the tentacles, and an anti-GABA B receptor antibody-labeled ring coincident with it. The location of this ring is consistent with the physiology of the hypostomal pacemaker systems of hydra. We also describe a distally located, ectodermal ring of nerve fibers that is not associated with anti-GABA B receptor antibody labeling. The neurites and cell bodies of sensory cells contribute to both rings. The location of the distal ring and its sensory cell neurites suggests an involvement in the behavior of the mouth. Between the two rings is a network of anastomosing sensory and ganglion cell bodies and their neurites. Phase contrast, darkfield, and antibody-labeled images reveal that the mouth of hydra comprises five or six epithelial folds whose endoderm extensively labels with anti-GABA B receptor antibody, suggesting that endodermal metabotrobic GABA receptors are also involved in regulating mouth behavior.

Branching out: origins of the sea urchin larval skeleton in development and evolution.

PubMed

McIntyre, Daniel C; Lyons, Deirdre C; Martik, Megan; McClay, David R

2014-03-01

It is a challenge to understand how the information encoded in DNA is used to build a three-dimensional structure. To explore how this works the assembly of a relatively simple skeleton has been examined at multiple control levels. The skeleton of the sea urchin embryo consists of a number of calcite rods produced by 64 skeletogenic cells. The ectoderm supplies spatial cues for patterning, essentially telling the skeletogenic cells where to position themselves and providing the factors for skeletal growth. Here, we describe the information known about how this works. First the ectoderm must be patterned so that the signaling cues are released from precise positions. The skeletogenic cells respond by initiating skeletogenesis immediately beneath two regions (one on the right and the other on the left side). Growth of the skeletal rods requires additional signaling from defined ectodermal locations, and the skeletogenic cells respond to produce a membrane-bound template in which the calcite crystal grows. Important in this process are three signals, fibroblast growth factor, vascular endothelial growth factor, and Wnt5. Each is necessary for explicit tasks in skeleton production. Copyright © 2014 Wiley Periodicals, Inc.

A rare case of malignant pediatric ectomesenchymoma arising from the cerebrum.

PubMed

Kun, Yao; Duan, Zejun; Mei, Xi; Xu, Ying; Li, Jiuzhou; Li, Shouwei; Qi, Xueling

2015-01-01

Malignant ectomesenchymoma is a rare tumor that contains both ectodermal and mesenchymal elements. So far, only 7 patients with a manifestation in the cerebrum (with confirmed clinicopathological data) have been reported. A 4-year-old girl was present at our hospital with a 3-week history of intermittent sudden dizzy with no apparent cause. MRI showed an irregular enhanced lesion in the left frontal-parietal lobe and lateral ventricle with peripheral gadolinium-enhancement with a significant surrounding edema. Total removal of the tumor was performed. Histological examination of the resected tumor revealed a mixed astrocytoma and anaplastic ependymoma component with undifferentiated mesenchymal spindle cell component. Generally speaking, the main malignant part in most cases of malignant ectomesenchymoma (MEM) is the mesenchymal component. In the present case, the malignant component was both in the mesenchymal and ectodermal part. In particular, the mesenchymal part was mainly composed of spindle cells, and the ectodermal part primarily consisted of gliomatous component and anaplastic ependymoma component. The patient was then treated with chemotherapy and as regard to the prognosis, there was no evidence of tumor recurrence at the 5 months' follow-up. The long term follow-up is still in progress.

Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

PubMed Central

Ferre, Elise M.N.; Rose, Stacey R.; Rosenzweig, Sergio D.; Burbelo, Peter D.; Romito, Kimberly R.; Niemela, Julie E.; Rosen, Lindsey B.; Break, Timothy J.; Gu, Wenjuan; Hunsberger, Sally; Browne, Sarah K.; Hsu, Amy P.; Rampertaap, Shakuntala; Swamydas, Muthulekha; Collar, Amanda L.; Kong, Heidi H.; Chascsa, David; Simcox, Thomas; Pham, Angela; Bondici, Anamaria; Natarajan, Mukil; Monsale, Joseph; Kleiner, David E.; Quezado, Martha; Alevizos, Ilias; Moutsopoulos, Niki M.; Yockey, Lynne; Frein, Cathleen; Soldatos, Ariane; Calvo, Katherine R.; Adjemian, Jennifer; Similuk, Morgan N.; Lang, David M.; Stone, Kelly D.; Uzel, Gulbu; Bishop, Rachel J.; Holland, Steven M.; Olivier, Kenneth N.; Fleisher, Thomas A.; Heller, Theo; Winer, Karen K.

2016-01-01

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE mutations. It classically presents with chronic mucocutaneous candidiasis and autoimmunity that primarily targets endocrine tissues; hypoparathyroidism and adrenal insufficiency are most common. Developing any two of these classic triad manifestations establishes the diagnosis. Although widely recognized in Europe, where nonendocrine autoimmune manifestations are uncommon, APECED is less defined in patients from the Western Hemisphere. We enrolled 35 consecutive American APECED patients (33 from the US) in a prospective observational natural history study and systematically examined their genetic, clinical, autoantibody, and immunological characteristics. Most patients were compound heterozygous; the most common AIRE mutation was c.967_979del13. All but one patient had anti–IFN-ω autoantibodies, including 4 of 5 patients without biallelic AIRE mutations. Urticarial eruption, hepatitis, gastritis, intestinal dysfunction, pneumonitis, and Sjögren’s-like syndrome, uncommon entities in European APECED cohorts, affected 40%–80% of American cases. Development of a classic diagnostic dyad was delayed at mean 7.38 years. Eighty percent of patients developed a median of 3 non-triad manifestations before a diagnostic dyad. Only 20% of patients had their first two manifestations among the classic triad. Urticarial eruption, intestinal dysfunction, and enamel hypoplasia were prominent among early manifestations. Patients exhibited expanded peripheral CD4+ T cells and CD21loCD38lo B lymphocytes. In summary, American APECED patients develop a diverse syndrome, with dramatic enrichment in organ-specific nonendocrine manifestations starting early in life, compared with European patients. Incorporation of these new manifestations into American diagnostic criteria would accelerate diagnosis by approximately 4 years and potentially prevent life-threatening endocrine complications. PMID:27588307

Evolution of Axis Specification Mechanisms in Jawed Vertebrates: Insights from a Chondrichthyan

PubMed Central

Coolen, Marion; Sauka-Spengler, Tatjana; Nicolle, Delphine; Le-Mentec, Chantal; Lallemand, Yvan; Silva, Corinne Da; Plouhinec, Jean-Louis; Robert, Benoît; Wincker, Patrick; Shi, De-Li; Mazan, Sylvie

2007-01-01

The genetic mechanisms that control the establishment of early polarities and their link with embryonic axis specification and patterning seem to substantially diverge across vertebrates. In amphibians and teleosts, the establishment of an early dorso-ventral polarity determines both the site of axis formation and its rostro-caudal orientation. In contrast, amniotes retain a considerable plasticity for their site of axis formation until blastula stages and rely on signals secreted by extraembryonic tissues, which have no clear equivalents in the former, for the establishment of their rostro-caudal pattern. The rationale for these differences remains unknown. Through detailed expression analyses of key development genes in a chondrichthyan, the dogfish Scyliorhinus canicula, we have reconstructed the ancestral pattern of axis specification in jawed vertebrates. We show that the dogfish displays compelling similarities with amniotes at blastula and early gastrula stages, including the presence of clear homologs of the hypoblast and extraembryonic ectoderm. In the ancestral state, these territories are specified at opposite poles of an early axis of bilateral symmetry, homologous to the dorso-ventral axis of amphibians or teleosts, and aligned with the later forming embryonic axis, from head to tail. Comparisons with amniotes suggest that a dorsal expansion of extraembryonic ectoderm, resulting in an apparently radial symmetry at late blastula stages, has taken place in their lineage. The synthesis of these results with those of functional analyses in model organisms supports an evolutionary link between the dorso-ventral polarity of amphibians and teleosts and the embryonic-extraembryonic organisation of amniotes. It leads to a general model of axis specification in gnathostomes, which provides a comparative framework for a reassessment of conservations both among vertebrates and with more distant metazoans. PMID:17440610

Differential expression of two scribble isoforms during Drosophila embryogenesis.

PubMed

Li, M; Marhold, J; Gatos, A; Török, I; Mechler, B M

2001-10-01

The tumour suppressor gene scribble (scrib) is required for epithelial polarity and growth control in Drosophila. Here, we report the identification and embryonic expression pattern of two Scrib protein isoforms resulting from alternative splicing during scrib transcription. Both proteins are first ubiquitously expressed during early embryogenesis. Then, during morphogenesis each Scrib protein displays a specific pattern of expression in the central and peripheral nervous systems, CNS and PNS, respectively. During germ band extension, the expression of the longer form Scrib1 occurs predominantly in the neuroblasts derived from the neuro-ectoderm and becomes later restricted to CNS neurones as well as to the pole cells in the gonads. By contrast, the shorter form Scrib2 is strongly expressed in the PNS and a subset of CNS neurones.

3D Bioprinting Human Induced Pluripotent Stem Cell Constructs for In Situ Cell Proliferation and Successive Multilineage Differentiation.

PubMed

Gu, Qi; Tomaskovic-Crook, Eva; Wallace, Gordon G; Crook, Jeremy M

2017-09-01

The ability to create 3D tissues from induced pluripotent stem cells (iPSCs) is poised to revolutionize stem cell research and regenerative medicine, including individualized, patient-specific stem cell-based treatments. There are, however, few examples of tissue engineering using iPSCs. Their culture and differentiation is predominantly planar for monolayer cell support or induction of self-organizing embryoids (EBs) and organoids. Bioprinting iPSCs with advanced biomaterials promises to augment efforts to develop 3D tissues, ideally comprising direct-write printing of cells for encapsulation, proliferation, and differentiation. Here, such a method, employing a clinically amenable polysaccharide-based bioink, is described as the first example of bioprinting human iPSCs for in situ expansion and sequential differentiation. Specifically, we have extrusion printed the bioink including iPSCs, alginate (Al; 5% weight/volume [w/v]), carboxymethyl-chitosan (5% w/v), and agarose (Ag; 1.5% w/v), crosslinked the bioink in calcium chloride for a stable and porous construct, proliferated the iPSCs within the construct and differentiated the same iPSCs into either EBs comprising cells of three germ lineages-endoderm, ectoderm, and mesoderm, or more homogeneous neural tissues containing functional migrating neurons and neuroglia. This defined, scalable, and versatile platform is envisaged being useful in iPSC research and translation for pharmaceuticals development and regenerative medicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Collagen-IV supported embryoid bodies formation and differentiation from buffalo (Bubalus bubalis) embryonic stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taru Sharma, G., E-mail: gts553@gmail.com; Dubey, Pawan K.; Verma, Om Prakash

Graphical abstract: EBs formation, characterization and expression of germinal layers marker genes of in vivo developed teratoma using four different types of extracellular matrices. Highlights: Black-Right-Pointing-Pointer Collagen-IV matrix is found cytocompatible for EBs formation and differentiation. Black-Right-Pointing-Pointer Established 3D microenvironment for ES cells development and differentiation into three germ layers. Black-Right-Pointing-Pointer Collagen-IV may be useful as promising candidate for ES cells based therapeutic applications. -- Abstract: Embryoid bodies (EBs) are used as in vitro model to study early extraembryonic tissue formation and differentiation. In this study, a novel method using three dimensional extracellular matrices for in vitro generation of EBsmore » from buffalo embryonic stem (ES) cells and its differentiation potential by teratoma formation was successfully established. In vitro derived inner cell masses (ICMs) of hatched buffalo blastocyst were cultured on buffalo fetal fibroblast feeder layer for primary cell colony formation. For generation of EBs, pluripotent ES cells were seeded onto four different types of extracellular matrices viz; collagen-IV, laminin, fibronectin and matrigel using undifferentiating ES cell culture medium. After 5 days of culture, ESCs gradually grew into aggregates and formed simple EBs having circular structures. Twenty-six days later, they formed cystic EBs over collagen matrix with higher EBs formation and greater proliferation rate as compared to other extracellular matrices. Studies involving histological observations, fluorescence microscopy and RT-PCR analysis of the in vivo developed teratoma revealed that presence of all the three germ layer derivatives viz. ectoderm (NCAM), mesoderm (Flk-1) and endoderm (AFP). In conclusion, the method described here demonstrates a simple and cost-effective way of generating EBs from buffalo ES cells. Collagen-IV matrix was found cytocompatible as it supported buffalo EBs formation, their subsequent differentiation could prove to be useful as promising candidate for ES cells based therapeutic applications.« less

Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma

PubMed Central

Georgy, Smitha R.; Cangkrama, Michael; Srivastava, Seema; Partridge, Darren; Auden, Alana; Dworkin, Sebastian; McLean, Catriona A.; Darido, Charbel

2015-01-01

Background: The developmental transcription factor Grainyhead-like 3 (GRHL3) plays a critical tumor suppressor role in the mammalian epidermis through direct regulation of PTEN and the PI3K/AKT/mTOR signaling pathway. GRHL3 is highly expressed in all tissues derived from the surface ectoderm, including the oral cavity, raising a question about its potential role in suppression of head and neck squamous cell carcinoma (HNSCC). Methods: We explored the tumor suppressor role of Grhl3 in HNSCC using a conditional knockout (Grhl3 ∆/– /K14Cre +) mouse line (n = 26) exposed to an oral chemical carcinogen. We defined the proto-oncogenic pathway activated in the HNSCC derived from these mice and assessed it in primary human HNSCC samples, normal oral epithelial cell lines carrying shRNA to GRHL3, and human HNSCC cell lines. Data were analyzed with two-sided chi square and Student’s t tests. Results: Deletion of Grhl3 in oral epithelium in mice did not perturb PTEN/PI3K/AKT/mTOR signaling, but instead evoked loss of GSK3B expression, resulting in stabilization and accumulation of c-MYC and aggressive HNSCC. This molecular signature was also evident in a subset of primary human HNSCC and HNSCC cell lines. Loss of Gsk3b in mice, independent of Grhl3, predisposed to chemical-induced HNSCC. Restoration of GSK3B expression blocked proliferation of normal oral epithelial cell lines carrying shRNA to GRHL3 (cell no., Day 8: Scramble ctl, 616±21.8 x 103 vs GRHL3-kd, 1194±44 X 103, P < .001; GRHL3-kd vs GRHL3-kd + GSK3B, 800±98.84 X 103, P = .003) and human HNSCC cells. Conclusions: We defined a novel molecular signature in mammalian HNSCC, suggesting new treatment strategies targeting the GRHL3/GSK3B/c-MYC proto-oncogenic network. PMID:26063791

Non-identical distribution pattern of epidermal growth factor and platelet-derived growth factor in the mouse uterus during the oestrous cycle and early pregnancy.

PubMed

Jaber, L; Kan, F W

1998-10-01

In the present study, we examined by immunohistochemistry the cell-specific distribution of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) in the mouse uterus during the oestrous cycle and throughout the first 7 days of pregnancy. Paraffin-embedded tissue samples were immunostained using the avidin-biotin peroxidase technique and then examined by light microscopy. Our results showed that immunostaining for EGF was detected in the stroma but not in the luminal or glandular epithelium. A high concentration of EGF was detected in the stroma around the time of embryo implantation at days 3, 4 and 5 of pregnancy. The implanted embryo at day 7 of gestation showed immunostaining for EGF between the ectoderm and endoderm layers. The cell distribution pattern for PDGF was found to be different from that observed with EGF. Luminal and glandular epithelia displayed PDGF immunostaining throughout the first 7 days of pregnancy, with the highest intensity at days 4 and 5 of gestation. In contrast, no immunostaining was observed in the luminal and glandular epithelia at post-oestrus, dioestrus and pro-oestrus stages. However, a weak reaction started to appear at oestrus. The embryo at the blastocyst stage displayed a strong immunoreaction for antibody against PDGF. In addition, the decidual boundary zone surrounding the implanted embryo at days 5, 6 and 7 of gestation also showed an immunostaining for PDGF. The present observations demonstrate clearly the presence of EGF and PDGF in the mouse uterus in high concentrations at the peri-implantation period. Thus, our results, together with what is known about the effect of EGF and PDGF in controlling the growth, differentiation and activation of a variety of cell types, suggest a possible role for these growth factors during the preparation of the endometrium for implantation in controlling the proliferation activity of stromal and/or epithelial cells.

The fungicide benomyl inhibits differentiation of neural tissue in the Xenopus embryo and animal cap explants.

PubMed

Yoon, Chun-Sik; Jin, Jung-Hyo; Park, Joo-Hung; Youn, Hyun-Joo; Cheong, Seon-Woo

2003-10-01

The toxic effect of benomyl on the embryogenesis of Xenopus laevis was investigated, and the tissues most affected by benomyl were identified. The toxicity of benomyl at various concentrations (5-20 microM) was tested with the Xenopus frog embryo teratogenesis assay (FETAX), used with slight modification. All test embryos subjected to 20 microM of benomyl died, and exposure to 10 and 15 microM benomyl produced growth inhibition and 11 types of severe external malformations. Histological examination of the test embryos showed dysplasia of the brain, eyes, intestine, otic vesicle, and muscle and swelling of the pronephric ducts and integuments. Among the tissues and organs affected, malformation of neural tissue was the most severe. The presumptive ectoderm isolated from st. 9 embryo was cultured in 10 ng/mL of activin A to induce neural tissue and mesoderm. When it was cultured with 10 ng/mL of activin A in the presence of 1 and 10 microM of benomyl, neural tissue induction was inhibited more severely than that of any other tissue. The gene expression of cultivated explants was investigated by reverse transcription-polymerase chain reaction (RT-PCR) assay in order to study the inhibition of neural tissue by benomyl. The results showed that with increasing benomyl concentration, the expression of the neural-specific marker NCAM (neural cell adhesion molecule), was more strongly inhibited than the muscle-specific marker muscle actin. Electron micrographs of test explants showed many residual yolk platelets and mitochondrial degeneration. In the present investigation the most severe toxic effects of benomyl were seen in the nerve tissues of the Xenopus embryo. This inhibition of neural development may have been caused by the inhibition of the assembly of neural microtubules and by the effect of benomyl on neuronal proliferation and migration. Copyright 2003 Wiley Periodicals, Inc.

[Rathke cysts, craniopharyngioma, and colloid cysts : What are the differences between these pathologies?

PubMed

Eymann, R; Kiefer, M

2018-05-17

Headache is the most common symptom of colloid cysts, Rathke cysts, and craniopharyngioma due to their location in the midline, being extra-axial and typically presenting in the parasellar region. Although these tumors are generally considered benign, each has its typical characteristics defined by its location and histology. These individual characteristics define whether surgery is necessary at all and if so, the preferred surgical approach and resection's totality. The histopathological findings primarily indicate that embryonic malformations-at the first glance, ectodermal in nature-cause these tumors. Due to the fact that these disturbances occur at the boundary between ectodermal stomodeum and endodermal cephalogaster, however, does leave some doubts.

The influence of cell interactions and tissue mass on differentiation of sea urchin mesomeres.

PubMed

Khaner, O; Wilt, F

1990-07-01

The developmental potential of different blastomeres of the sea urchin embryo was re-examined. We have employed a new method to isolate substantial numbers of different kinds of blastomeres from 16-cell-stage embryos, and we have used newly available molecular markers to analyze possible vegetal differentiation. We have found that, while isolated mesomere pairs behave according to the classical expectations and develop into ectodermal vesicles, there is a clear effect of reaggregating two or more mesomere pairs. They survive better in long-term culture and, after prolonged periods, they display an astonishing ability to express vegetal differentiation. We also combined mesomeres with stained micromeres or macromeres from the vegetal hemisphere. Although induction of guts and spicules was observed, there was little if any effect of varying the ratio of different blastomeres on the kinds of differentiation obtained.

Methods to Manipulate and Monitor Wnt Signaling in Human Pluripotent Stem Cells.

PubMed

Huggins, Ian J; Brafman, David; Willert, Karl

2016-01-01

Human pluripotent stem cells (hPSCs) may revolutionize medical practice by providing: (a) a renewable source of cells for tissue replacement therapies, (b) a powerful system to model human diseases in a dish, and (c) a platform for examining efficacy and safety of novel drugs. Furthermore, these cells offer a unique opportunity to study early human development in vitro, in particular, the process by which a seemingly uniform cell population interacts to give rise to the three main embryonic lineages: ectoderm, endoderm. and mesoderm. This process of lineage allocation is regulated by a number of inductive signals that are mediated by growth factors, including FGF, TGFβ, and Wnt. In this book chapter, we introduce a set of tools, methods, and protocols to specifically manipulate the Wnt signaling pathway with the intention of altering the cell fate outcome of hPSCs.

N-myc regulates growth and fiber cell differentiation in lens development

PubMed Central

Cavalheiro, Gabriel R.; Matos-Rodrigues, Gabriel E.; Zhao, Yilin; Gomes, Anielle L.; Anand, Deepti; Predes, Danilo; de Lima, Silmara; Abreu, Jose G.; Zheng, Deyou; Lachke, Salil A.; Cvekl, Ales; Martins, Rodrigo A. P.

2017-01-01

Myc proto-oncogenes regulate diverse cellular processes during development, but their roles during morphogenesis of specific tissues are not fully understood. We found that c-myc regulates cell proliferation in mouse lens development and previous genome-wide studies suggested functional roles for N-myc in developing lens. Here, we examined the role of N-myc in mouse lens development. Genetic inactivation of N-myc in the surface ectoderm or lens vesicle impaired eye and lens growth, while "late" inactivation in lens fibers had no effect. Unexpectedly, defective growth of N-myc--deficient lenses was not associated with alterations in lens progenitor cell proliferation or survival. Notably, N-myc-deficient lens exhibited a delay in degradation of DNA in terminally differentiating lens fiber cells. RNA-sequencing analysis of N-myc--deficient lenses identified a cohort of down-regulated genes associated with fiber cell differentiation that included DNaseIIβ. Further, an integrated analysis of differentially expressed genes in N-myc-deficient lens using normal lens expression patterns of iSyTE, N-myc-binding motif analysis and molecular interaction data from the String database led to the derivation of an N-myc-based gene regulatory network in the lens. Finally, analysis of N-myc and c-myc double-deficient lens demonstrated that these Myc genes cooperate to drive lens growth prior to lens vesicle stage. Together, these findings provide evidence for exclusive and cooperative functions of Myc transcription factors in mouse lens development and identify novel mechanisms by which N-myc regulates cell differentiation during eye morphogenesis. PMID:28716713

T-Box Genes in Drosophila Limb Development.

PubMed

Pflugfelder, G O; Eichinger, F; Shen, J

2017-01-01

T-box genes are essential for limb development in vertebrates and arthropods. The Drosophila genome encodes eight T-box genes, six of which are expressed in limb ontogenesis. The Tbx20-related gene pair midline and H15 is essential for dorso-ventral patterning of the Drosophila legs. The three Tbx6-related Dorsocross genes are required for epithelial remodeling during wing development. The Drosophila gene optomotor-blind (omb) is the only member of the Tbx2 subfamily in the fly and is predominantly involved in wing development. Omb is essential for wing development and is sufficient to promote the development of a second wing pair. Targeted manipulations of omb expression have shown that the bulk omb requirement for wing development can be deconstructed into a number of individual functions. Even though omb expression in the wing disc is symmetrical with regard to the anterior/posterior (A/P) compartment boundary, anterior and posterior knockdowns have distinct consequences: Anterior Omb is required for the maintenance of a straight A/P lineage restriction boundary. Posterior Omb suppresses formation of an apical epithelial fold along the A/P boundary. Drosophila T-box gene expression is not confined to the ectoderm-derived epithelia of the imaginal discs. Both Doc and Omb are prominently expressed in leg disc muscle precursor cells. Omb is also strongly expressed in a tracheal branch that invades the extracellular matrix of the wing disc. The function of Doc and Omb in the latter tissues is not known, indicative of the many questions still open in the field. © 2017 Elsevier Inc. All rights reserved.

Early events in xenograft development from the human embryonic stem cell line HS181--resemblance with an initial multiple epiblast formation.

PubMed

Gertow, Karin; Cedervall, Jessica; Jamil, Seema; Ali, Rouknuddin; Imreh, Marta P; Gulyas, Miklos; Sandstedt, Bengt; Ahrlund-Richter, Lars

2011-01-01

Xenografting is widely used for assessing in vivo pluripotency of human stem cell populations. Here, we report on early to late events in the development of mature experimental teratoma from a well-characterized human embryonic stem cell (HESC) line, HS181. The results show an embryonic process, increasingly chaotic. Active proliferation of the stem cell derived cellular progeny was detected already at day 5, and characterized by the appearance of multiple sites of engraftment, with structures of single or pseudostratified columnar epithelium surrounding small cavities. The striking histological resemblance to developing embryonic ectoderm, and the formation of epiblast-like structures was supported by the expression of the markers OCT4, NANOG, SSEA-4 and KLF4, but a lack of REX1. The early neural marker NESTIN was uniformly expressed, while markers linked to gastrulation, such as BMP-4, NODAL or BRACHYURY were not detected. Thus, observations on day 5 indicated differentiation comparable to the most early transient cell populations in human post implantation development. Confirming and expanding on previous findings from HS181 xenografts, these early events were followed by an increasingly chaotic development, incorporated in the formation of a benign teratoma with complex embryonic components. In the mature HS181 teratomas not all types of organs/tissues were detected, indicating a restricted differentiation, and a lack of adequate spatial developmental cues during the further teratoma formation. Uniquely, a kinetic alignment of rare complex structures was made to human embryos at diagnosed gestation stages, showing minor kinetic deviations between HS181 teratoma and the human counterpart.

Axisymmetric drop shape analysis for estimating the surface tension of cell aggregates by centrifugation.

PubMed

Kalantarian, Ali; Ninomiya, Hiromasa; Saad, Sameh M I; David, Robert; Winklbauer, Rudolf; Neumann, A Wilhelm

2009-02-18

Biological tissues behave in certain respects like liquids. Consequently, the surface tension concept can be used to explain aspects of the in vitro and in vivo behavior of multicellular aggregates. Unfortunately, conventional methods of surface tension measurement cannot be readily applied to small cell aggregates. This difficulty can be overcome by an experimentally straightforward method consisting of centrifugation followed by axisymmetric drop shape analysis (ADSA). Since the aggregates typically show roughness, standard ADSA cannot be applied and we introduce a novel numerical method called ADSA-IP (ADSA for imperfect profile) for this purpose. To examine the new methodology, embryonic tissues from the gastrula of the frog, Xenopus laevis, deformed in the centrifuge are used. It is confirmed that surface tension measurements are independent of centrifugal force and aggregate size. Surface tension is measured for ectodermal cells in four sample batches, and varies between 1.1 and 7.7 mJ/m2. Surface tension is also measured for aggregates of cells expressing cytoplasmically truncated EP/C-cadherin, and is approximately half as large. In parallel, such aggregates show a reduction in convergent extension-driven elongation after activin treatment, reflecting diminished intercellular cohesion.

Self-organization of neural patterns and structures in 3D culture of stem cells

NASA Astrophysics Data System (ADS)

Sasai, Yoshiki

2013-05-01

Over the last several years, much progress has been made for in vitro culture of mouse and human ES cells. Our laboratory focuses on the molecular and cellular mechanisms of neural differentiation from pluripotent cells. Pluripotent cells first become committed to the ectodermal fate and subsequently differentiate into uncommitted neuroectodermal cells. Both previous mammalian and amphibian studies on pluripotent cells have indicated that the neural fate is a sort of the basal direction of the differentiation of these cells while mesoendodermal differentiation requires extrinsic inductive signals. ES cells differentiate into neuroectodermal cells with a rostral-most character (telencephalon and hypothalamus) when they are cultured in the absence of strong patterning signals. In this talk, I first discuss this issue by referring to our recent data on the mechanism of spontaneous neural differentiation in serum-free culture of mouse ES cells. Then, I will talk about self-organization phenomena observed in 3D culture of ES cells, which lead to tissue-autonomous formation of regional structures such as layered cortical tissues. I also discuss our new attempt to monitor these in vitro morphogenetic processes by live imaging, in particular, self-organizing morphogenesis of the optic cup in three-dimensional cultures.

Generation of transgenic Hydra by embryo microinjection.

PubMed

Juliano, Celina E; Lin, Haifan; Steele, Robert E

2014-09-11

As a member of the phylum Cnidaria, the sister group to all bilaterians, Hydra can shed light on fundamental biological processes shared among multicellular animals. Hydra is used as a model for the study of regeneration, pattern formation, and stem cells. However, research efforts have been hampered by lack of a reliable method for gene perturbations to study molecular function. The development of transgenic methods has revitalized the study of Hydra biology(1). Transgenic Hydra allow for the tracking of live cells, sorting to yield pure cell populations for biochemical analysis, manipulation of gene function by knockdown and over-expression, and analysis of promoter function. Plasmid DNA injected into early stage embryos randomly integrates into the genome early in development. This results in hatchlings that express transgenes in patches of tissue in one or more of the three lineages (ectodermal epithelial, endodermal epithelial, or interstitial). The success rate of obtaining a hatchling with transgenic tissue is between 10% and 20%. Asexual propagation of the transgenic hatchling is used to establish a uniformly transgenic line in a particular lineage. Generating transgenic Hydra is surprisingly simple and robust, and here we describe a protocol that can be easily implemented at low cost.

Neurotoxin localization to ectodermal gland cells uncovers an alternative mechanism of venom delivery in sea anemones.

PubMed

Moran, Yehu; Genikhovich, Grigory; Gordon, Dalia; Wienkoop, Stefanie; Zenkert, Claudia; Ozbek, Suat; Technau, Ulrich; Gurevitz, Michael

2012-04-07

Jellyfish, hydras, corals and sea anemones (phylum Cnidaria) are known for their venomous stinging cells, nematocytes, used for prey and defence. Here we show, however, that the potent Type I neurotoxin of the sea anemone Nematostella vectensis, Nv1, is confined to ectodermal gland cells rather than nematocytes. We demonstrate massive Nv1 secretion upon encounter with a crustacean prey. Concomitant discharge of nematocysts probably pierces the prey, expediting toxin penetration. Toxin efficiency in sea water is further demonstrated by the rapid paralysis of fish or crustacean larvae upon application of recombinant Nv1 into their medium. Analysis of other anemone species reveals that in Anthopleura elegantissima, Type I neurotoxins also appear in gland cells, whereas in the common species Anemonia viridis, Type I toxins are localized to both nematocytes and ectodermal gland cells. The nematocyte-based and gland cell-based envenomation mechanisms may reflect substantial differences in the ecology and feeding habits of sea anemone species. Overall, the immunolocalization of neurotoxins to gland cells changes the common view in the literature that sea anemone neurotoxins are produced and delivered only by stinging nematocytes, and raises the possibility that this toxin-secretion mechanism is an ancestral evolutionary state of the venom delivery machinery in sea anemones.

Activin- and Nodal-related factors control antero-posterior patterning of the zebrafish embryo.

PubMed

Thisse, B; Wright, C V; Thisse, C

2000-01-27

Definition of cell fates along the dorso-ventral axis depends on an antagonistic relationship between ventralizing transforming growth factor-beta superfamily members, the bone morphogenetic proteins and factors secreted from the dorsal organizer, such as Noggin and Chordin. The extracellular binding of the last group to the bone morphogenetic proteins prevents them from activating their receptors, and the relative ventralizer:antagonist ratio is thought to specify different dorso-ventral cell fates. Here, by taking advantage of a non-genetic interference method using a specific competitive inhibitor, the Lefty-related gene product Antivin, we provide evidence that cell fate along the antero-posterior axis of the zebrafish embryo is controlled by the morphogenetic activity of another transforming growth factor-beta superfamily subgroup--the Activin and Nodal-related factors. Increasing antivin doses progressively deleted posterior fates within the ectoderm, eventually resulting in the removal of all fates except forebrain and eyes. In contrast, overexpression of activin or nodal-related factors converted ectoderm that was fated to be forebrain into more posterior ectodermal or mesendodermal fates. We propose that modulation of intercellular signalling by Antivin/Activin and Nodal-related factors provides a mechanism for the graded establishment of cell fates along the antero-posterior axis of the zebrafish embryo.

The development of the eyelids. Part I. External features.

PubMed

Pearson, A A

1980-01-01

The sequence of developmental events leading to the formation of the eyelids is described in staged human embryos. By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode (Stage 13). A few days later (about 32 days, Stage 14) the lens placode is indented by the lens pit. A day or two later (about 33 days, Stage 15) the lens pit is closed: however, the lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it (stage 16, 37 days). As these grooves deepen, in Stages 17--19, eyelid folds develop, first below, and then above, the eye. In Stages 19--22 the eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19. The inner canthus is established a few days later in Stage 20. Closure of the eyelids is complete in Stage 23.

Foxi2 Is an Animally Localized Maternal mRNA in Xenopus, and an Activator of the Zygotic Ectoderm Activator Foxi1e

PubMed Central

Cha, Sang-Wook; McAdams, Meredith; Kormish, Jay; Wylie, Christopher; Kofron, Matthew

2012-01-01

Foxi1e is a zygotic transcription factor that is essential for the expression of early ectodermal genes. It is expressed in a highly specific pattern, only in the deep cell layers of the animal hemisphere, and in a mosaic pattern in which expressing cells are interspersed with non-expressing cells. Previous work has shown that several signals in the blastula control this expression pattern, including nodals, the TGFβ family member Vg1, and Notch. However, these are all inhibitory, which raises the question of what activates Foxi1e. In this work, we show that a related Forkhead family protein, Foxi2, is a maternal activator of Foxi1e. Foxi2 mRNA is maternally encoded, and highly enriched in animal hemisphere cells of the blastula. ChIP assays show that it acts directly on upstream regulatory elements of Foxi1e. Its effect is specific, since animal cells depleted of Foxi2 are able to respond normally to mesoderm inducing signals from vegetal cells. Foxi2 thus acts as a link between the oocyte and the early pathway to ectoderm, in a similar fashion to the vegetally localized VegT acts to initiate endoderm and mesoderm formation. PMID:22848601

An historical perspective on the pioneering experiments of John Saunders.

PubMed

Tickle, Cheryll

2017-09-15

John Saunders was a highly skilled embryologist who pioneered the study of limb development. His studies on chick embryos provided the fundamental framework for understanding how vertebrate limbs develop. This framework inspired generations of scientists and formed the bridge from experimental embryology to molecular mechanisms. Saunders investigated how feathers become organized into tracts in the skin of the chick wing and also identified regions of programmed cell death. He discovered that a region of thickened ectoderm that rims the chick wing bud - the apical ectodermal ridge - is required for outgrowth and the laying down of structures along the proximo-distal axis (long axis) of the wing, identified the zone of polarizing activity (ZPA; polarizing region) that controls development across the anteroposterior axis ("thumb to little finger "axis) and contributed to uncovering the importance of the ectoderm in development of structures along the dorso-ventral axis ( "back of hand to palm" axis). This review looks in depth at some of his original papers and traces how he made the crucial findings about how limbs develop, considering these findings both in the context of contemporary knowledge at the time and also in terms of their immediate impact on the field. Copyright © 2017 Elsevier Inc. All rights reserved.

The Ca2+-induced methyltransferase xPRMT1b controls neural fate in amphibian embryo.

PubMed

Batut, Julie; Vandel, Laurence; Leclerc, Catherine; Daguzan, Christiane; Moreau, Marc; Néant, Isabelle

2005-10-18

We have previously shown that an increase in intracellular Ca2+ is both necessary and sufficient to commit ectoderm to a neural fate in Xenopus embryos. However, the relationship between this Ca2+ increase and the expression of early neural genes has yet to be defined. Using a subtractive cDNA library between untreated and caffeine-treated animal caps, i.e., control ectoderm and ectoderm induced toward a neural fate by a release of Ca2+, we have isolated the arginine N-methyltransferase, xPRMT1b, a Ca2+-induced target gene, which plays a pivotal role in this process. First, we show in embryo and in animal cap that xPRMT1b expression is Ca2+-regulated. Second, overexpression of xPRMT1b induces the expression of early neural genes such as Zic3. Finally, in the whole embryo, antisense approach with morpholino oligonucleotide against xPRMT1b impairs neural development and in animal caps blocks the expression of neural markers induced by a release of internal Ca2+. Our results implicate an instructive role of an enzyme, an arginine methyltransferase protein, in the embryonic choice of determination between epidermal and neural fate. The results presented provide insights by which a Ca2+ increase induces neural fate.

Ordered progression of nematogenesis from stem cells through differentiation stages in the tentacle bulb of Clytia hemisphaerica (Hydrozoa, Cnidaria).

PubMed

Denker, Elsa; Manuel, Michaël; Leclère, Lucas; Le Guyader, Hervé; Rabet, Nicolas

2008-03-01

Nematogenesis, the production of stinging cells (nematocytes) in Cnidaria, can be considered as a model neurogenic process. Most molecular data concern the freshwater polyp Hydra, in which nematocyte production is scattered throughout the body column ectoderm, the mature cells then migrating to the tentacles. We have characterized tentacular nematogenesis in the Clytia hemisphaerica hydromedusa and found it to be confined to the ectoderm of the tentacle bulb, a specialized swelling at the tentacle base. Analysis by a variety of light and electron microscope techniques revealed that while cellular aspects of nematogenesis are similar to Hydra, the spatio-temporal characteristics are markedly more ordered. The tentacle bulb nematogenic ectoderm (TBE) was found to be polarized, with a clear progression of successive nematoblast stages from a proximal zone (comprising a majority of undifferentiated cells) to the distal end where the tentacle starts. Pulse-chase labelling experiments demonstrated a continuous displacement of differentiating nematoblasts towards the tentacle tip, and that nematogenesis proceeds more rapidly in Clytia than in Hydra. Compact expression domains of orthologues of known nematogenesis-associated genes (Piwi, dickkopf-3, minicollagens and NOWA) were correspondingly staggered along the TBE. These distinct characteristics make the Clytia TBE a promising experimental system for understanding the mechanisms regulating nematogenesis.

Patterns of oriented cell division during the steady-state morphogenesis of the body column in hydra.

PubMed

Shimizu, H; Bode, P M; Bode, H R

1995-12-01

In an adult hydra, the tissue of the body column is in a dynamic state. The epithelial cells of both layers are constantly in the mitotic cycle. As the tissue expands, it is continuously displaced along the body axis in either an apical or basal direction, but not in a circumferential direction. Using a modified whole mount method we examined the orientation of mitotic spindles to determine what role the direction of cell division plays in axial displacement. Surprisingly, the direction of cell division was found to differ in the two epithelial layers. In the ectoderm it was somewhat biased in an axial direction. In the endoderm it was strongly biased in a circumferential direction. For both layers, the directional biases occurred throughout the length of the body column, with some regional variation in its extent. As buds developed into adults, the bias in each layer increased from an almost random distribution to the distinctly different orientations of the adult. Thus, to maintain the observed axial direction of tissue displacement, rearrangement of the epithelial cells of both layers must occur continuously in the adult as well as in developing animals. How the locomotory and contractile behavior of the muscle processes of the epithelial cells may effect changes in cell shape, and thereby influence the direction of cell division in each layer, is discussed.

A computational model for BMP movement in sea urchin embryos.

PubMed

van Heijster, Peter; Hardway, Heather; Kaper, Tasso J; Bradham, Cynthia A

2014-12-21

Bone morphogen proteins (BMPs) are distributed along a dorsal-ventral (DV) gradient in many developing embryos. The spatial distribution of this signaling ligand is critical for correct DV axis specification. In various species, BMP expression is spatially localized, and BMP gradient formation relies on BMP transport, which in turn requires interactions with the extracellular proteins Short gastrulation/Chordin (Chd) and Twisted gastrulation (Tsg). These binding interactions promote BMP movement and concomitantly inhibit BMP signaling. The protease Tolloid (Tld) cleaves Chd, which releases BMP from the complex and permits it to bind the BMP receptor and signal. In sea urchin embryos, BMP is produced in the ventral ectoderm, but signals in the dorsal ectoderm. The transport of BMP from the ventral ectoderm to the dorsal ectoderm in sea urchin embryos is not understood. Therefore, using information from a series of experiments, we adapt the mathematical model of Mizutani et al. (2005) and embed it as the reaction part of a one-dimensional reaction-diffusion model. We use it to study aspects of this transport process in sea urchin embryos. We demonstrate that the receptor-bound BMP concentration exhibits dorsally centered peaks of the same type as those observed experimentally when the ternary transport complex (Chd-Tsg-BMP) forms relatively quickly and BMP receptor binding is relatively slow. Similarly, dorsally centered peaks are created when the diffusivities of BMP, Chd, and Chd-Tsg are relatively low and that of Chd-Tsg-BMP is relatively high, and the model dynamics also suggest that Tld is a principal regulator of the system. At the end of this paper, we briefly compare the observed dynamics in the sea urchin model to a version that applies to the fly embryo, and we find that the same conditions can account for BMP transport in the two types of embryos only if Tld levels are reduced in sea urchin compared to fly. Copyright © 2014 Elsevier Ltd. All rights reserved.

DLX5, FGF8 and the Pin1 isomerase control ΔNp63α protein stability during limb development: a regulatory loop at the basis of the SHFM and EEC congenital malformations

PubMed Central

Restelli, Michela; Lopardo, Teresa; Lo Iacono, Nadia; Garaffo, Giulia; Conte, Daniele; Rustighi, Alessandra; Napoli, Marco; Del Sal, Giannino; Perez-Morga, David; Costanzo, Antonio; Merlo, Giorgio Roberto; Guerrini, Luisa

2014-01-01

Ectrodactyly, or Split-Hand/Foot Malformation (SHFM), is a congenital condition characterized by the loss of central rays of hands and feet. The p63 and the DLX5;DLX6 transcription factors, expressed in the embryonic limb buds and ectoderm, are disease genes for these conditions. Mutations of p63 also cause the ectodermal dysplasia–ectrodactyly–cleft lip/palate (EEC) syndrome, comprising SHFM. Ectrodactyly is linked to defects of the apical ectodermal ridge (AER) of the developing limb buds. FGF8 is the key signaling molecule in this process, able to direct proximo-distal growth and patterning of the skeletal primordial of the limbs. In the limb buds of both p63 and Dlx5;Dlx6 murine models of SHFM, the AER is poorly stratified and FGF8 expression is severely reduced. We show here that the FGF8 locus is a downstream target of DLX5 and that FGF8 counteracts Pin1–ΔNp63α interaction. In vivo, lack of Pin1 leads to accumulation of the p63 protein in the embryonic limbs and ectoderm. We show also that ΔNp63α protein stability is negatively regulated by the interaction with the prolyl-isomerase Pin1, via proteasome-mediated degradation; p63 mutant proteins associated with SHFM or EEC syndromes are resistant to Pin1 action. Thus, DLX5, p63, Pin1 and FGF8 participate to the same time- and location-restricted regulatory loop essential for AER stratification, hence for normal patterning and skeletal morphogenesis of the limb buds. These results shed new light on the molecular mechanisms at the basis of the SHFM and EEC limb malformations. PMID:24569166

EDAR-induced hypohidrotic ectodermal dysplasia: a clinical study on signs and symptoms in individuals with a heterozygous c.1072C > T mutation

PubMed Central

2014-01-01

Background Mutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia, however, the oral phenotype has been described in a limited number of cases. The aim of the present study was to clinically describe individuals with the c.1072C > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and saliva secretion, symptoms from other ectodermal structures and to assess orofacial function. Methods Individuals in three families living in Sweden, where some members had a known c.1072C > T mutation in the EDAR gene with an autosomal dominant inheritance (AD), were included in a clinical investigation on oral signs and symptoms and self-reported symptoms from other ectodermal structures (n = 37). Confirmation of the c.1072C > T mutation in the EDAR gene were performed by genomic sequencing. Orofacial function was evaluated with NOT-S. Results The mutation was identified in 17 of 37 family members. The mean number of missing teeth due to agenesis was 10.3 ± 4.1, (range 4–17) in the mutation group and 0.1 ± 0.3, (range 0–1) in the non-mutation group (p < 0.01). All individuals with the mutation were missing the maxillary lateral incisors and one or more of the mandibular incisors; and 81.3% were missing all four. Stimulated saliva secretion was 0.9 ± 0.5 ml/min in the mutation group vs 1.7 ± 0.6 ml/min in the non-mutation group (p < 0.01). Reduced ability to sweat was reported by 82% in the mutation group and by 20% in the non-mutation group (p < 0.01). The mean NOT-S score was 3.0 ± 1.9 (range 0–6) in the mutation group and 1.5 ± 1.1 (range 0–5) in the non-mutation group (p < 0.01). Lisping was present in 56% of individuals in the mutation group. Conclusions Individuals with a c.1072C > T mutation in the EDAR-gene displayed a typical pattern of congenitally missing teeth in the frontal area with functional consequences. They therefore have a need for special attention in dental care, both with reference to tooth agenesis and low salivary secretion with an increased risk for caries. Sweating problems were the most frequently reported symptom from other ectodermal structures. PMID:24884697

High-resolution mapping of the x-linked hypohidrotic ectodermal dysplasia (EDA) locus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zonana, J.; Jones, M.; Litt, M.

1992-11-01

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. The authors have extended previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analysis gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci couldmore » be inferred from a human-rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosites of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that consegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXSA732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively. 36 refs., 1 fig., 5 tabs.« less

Compartmentalization of the somite and myogenesis in chick embryos are influenced by wnt expression.

PubMed

Wagner, J; Schmidt, C; Nikowits, W; Christ, B

2000-12-01

Muscles of the body and bones of the axial skeleton derive from specialized regions of somites. Somite development is influenced by adjacent structures. In particular, the dorsal neural tube and the overlying ectoderm have been shown to be necessary for the induction of myogenic precursor cells in the dermomyotome. Members of the Wnt family of signaling molecules, which are expressed in the dorsal neural tube and the ectoderm, are postulated to be responsible for this process. It is shown here that ectopically implanted Wnt-1-, -3a-, and -4-expressing cells alter the process of somite compartmentalization in vivo. An enlarged dorsal compartment results from the implantation of Wnt-expressing cells ventrally between the neural tube/notochord and epithelial somites, at the expense of the ventral compartment, the sclerotome. Thus, ectopic Wnt expression is able to override the influence of ventralizing signals arising from notochord and floor plate. This shift of the border between the two compartments was identified by an increase in the domain of Pax-3 expression and a complete loss of Pax-1 expression in somites close to the ectopic Wnt signal. The expanded expression of MyoD and desmin provides evidence that it is the myotome which increases as a result of Wnt signaling. Paraxis expression is also drastically amplified after implantation of Wnt-expressing cells indicating that Wnts are involved in the formation and maintenance of somite epithelium and suggesting that Paraxis is activated through Wnt signaling pathways. Taken together these results suggest that ectopic Wnts disturb the normal balance of signaling molecules within the somite, resulting in an enhanced recruitment of somitic cells into the myogenic lineage. Copyright 2000 Academic Press.

Dermatologic findings of focal dermal hypoplasia (Goltz syndrome).

PubMed

Bree, Alanna F; Grange, Dorothy K; Hicks, M John; Goltz, Robert W

2016-03-01

Goltz syndrome, caused by mutations in PORCN, is an X-linked dominant ectodermal dysplasia which is also known as focal dermal hypoplasia. This name is derived from the predominant pathologic skin findings of the syndrome. Nineteen Goltz-affected participants attended a multidisciplinary scientific and clinical conference convened by the National Foundation for Ectodermal Dysplasia which allowed further characterization of the features of this very rare condition. At birth, the affected areas of skin are typically erythematous and fragile. The hallmark cutaneous features, which vary widely due to mosacism and X-inactivation, include the previously described skin changes of asymmetric Blaschko-linear and reticulated atrophy, pigmentary changes, and telangectasias. Lipomatous changes and papillomas as characteristically defined were reported in the majority of patients. A newly recognized skin finding was progressive hyperpigmented freckling that occurred within the hypopigmented areas which were noted to be photosensitive. Many patients also had a pebbly texture to the central face, dorsal hands and feet. Punctate erosions within the atrophic areas and hypohidrosis were also common. Most had patchy alopecia and many had diffusely thin hair. Scanning electron microscopy of the hair shafts revealed abnormalities in the majority of participants with several different features identified, including atrophic hairs with reduced diameters, markedly flattened hairs as noted in cross-sectional views, trichorrhexis nodosa, pili torti, and pili trianguli et canaliculi. Nail changes included V-nicking and longitudinal ridging of the nail plate, in addition to micronychia. Early recognition of the dermatologic features, in addition to the variable but universal limb anomalies, of Goltz syndrome will allow early and accurate diagnosis without the need for extensive diagnostic studies, while also allowing for accurate prognosis and appropriate genetic counseling. © 2016 Wiley Periodicals, Inc.

Establishment of human induced pluripotent stem cell lines from normal fibroblast TIG-1.

PubMed

Kumazaki, Tsutomu; Kurata, Sayaka; Matsuo, Taira; Mitsui, Youji; Takahashi, Tomoko

2011-06-01

Normal human cells have a replicative life span and therefore senesce. Usually, normal human cell strains are differentiated cells and reach a terminally differentiated state after a number of cell divisions. At present, definitive differences are not known between replicative senescence and terminal differentiation. TIG-1 is a human fibroblast strain established from fetal lung and has been used extensively in studies of cellular senescence, and numerous data were accumulated at the molecular level. Recently, a method for generating induced pluripotent stem cells (iPSCs) was developed. Using the method, we introduced four reprogramming genes to TIG-1 fibroblasts and succeeded in isolating colonies that had embryonic stem cell (ESC)-like morphologies. They showed alkaline phosphatase activity and expressed ESC markers, as shown by immunostaining of OCT4, SOX2, SSEA4, and TRA-1-81 as well as reverse-transcription polymerase chain reaction (RT-PCR) for OCT4 and NANOG transcripts. Thus, we succeeded in establishing iPSC clones from TIG-1. The iPSC clones could differentiate to cells originated from all three germ-cell layers, as shown by RT-PCR, for messenger RNA (mRNA) expression of α-fetoprotein (endoderm), MSX1 (mesoderm) and microtubule-associated protein 2 (ectoderm), and by immunostaining for α-fetoprotein (endoderm), α-smooth muscle actin (mesoderm), and β-III-tubulin (ectoderm). The iPSCs formed teratoma containing the structures developed from all three germ-cell layers in severe combined immune-deficiency mice. Thus, by comparing the aging process of parental TIG-1 cells and the differentiation process of iPSC-derived fibrocytes to fibroblasts, we can reveal the exact differences in processes between senescence and terminal differentiation.

Type II first branchial cleft anomaly.

PubMed

Al-Mahdi, Akmam H; Al-Khurri, Luay E; Atto, Ghada Z; Dhaher, Ameer

2013-01-01

First branchial cleft anomaly is a rare disease of the head and neck. It accounts for less than 8% of all branchial abnormalities. It is classified into type I, which is thought to arise from the duplication of the membranous external ear canal and are composed of ectoderm only, and type II that have ectoderm and mesoderm. Because of its rarity, first branchial cleft anomaly is often misdiagnosed and results in inappropriate management. A 9-year-old girl presented to us with fistula in the submandibular region and discharge in the external ear. Under general anesthesia, complete surgical excision of the fistula tract was done through step-ladder approach, and the histopathologic examination confirmed the diagnosis of type II first branchial cleft anomaly.

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia.

PubMed

Schneider, Holm; Faschingbauer, Florian; Schuepbach-Mallepell, Sonia; Körber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk-Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; Rascher, Wolfgang; Beckmann, Matthias W; Schneider, Pascal

2018-04-26

Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).

Equivalency of Buffalo (Bubalus Bubalis) Embryonic Stem Cells Derived From Fertilized, Parthenogenetic, and Hand-Made Cloned Embryos

PubMed Central

Muzaffar, Musharifa; Selokar, Naresh L.; Singh, Karn P.; Zandi, Mohammad; Singh, Manoj K.; Shah, Riaz A.; Chauhan, Manmohan S.; Singla, Suresh K.; Palta, Prabhat

2012-01-01

Abstract This study was aimed at establishing buffalo embryonic stem cells (ESCs) from in vitro fertilized (IVF), parthenogenetic, and hand-made cloned (HMC) embryos and to check their equivalency in terms of stem cell marker expression, longevity, proliferation, and differentiation pattern. ESCs derived from all three sources were found by immunofluorescence to express the pluripotency markers SSEA-4, TRA-1-60, TRA-1-81, OCT4, and SOX2 and were able to form embryoid bodies containing cells expressing genes specific to endoderm (AFP, HNF4, and GATA4), mesoderm (MSX1, BMP4, and ASA), and ectoderm (cytokeratin 8 and NF68). Reverse transcriptase PCR (RT-PCR) showed cells from all sources to be positive for pluripotency markers OCT4, SOX2, NANOG, STAT3, REX1, FOXD3, NUCLEOSTEMIN, and TELOMERASE. Pluripotency markers OCT4, SOX2, NANOG, and c-MYC were also analyzed by real-time PCR. No significant differences were observed among ESCs from all three sources for all these genes except NANOG, whose expression was higher (p<0.05) in HMC-derived ESCs (6.897±2.3) compared to that in parthenogenesis- and IVF-derived cells (1.603±0.315 and 1±0, respectively). Pluripotent, stable buffalo ESC lines derived from IVF, parthenogenesis, and HMC embryos may be genetically manipulated to provide a powerful tool for studies involving embryonic development, genomic imprinting, gene targeting, cloning, chimera formation, and transgenic animal production. PMID:22582863

Equivalency of buffalo (Bubalus bubalis) embryonic stem cells derived from fertilized, parthenogenetic, and hand-made cloned embryos.

PubMed

Muzaffar, Musharifa; Selokar, Naresh L; Singh, Karn P; Zandi, Mohammad; Singh, Manoj K; Shah, Riaz A; Chauhan, Manmohan S; Singla, Suresh K; Palta, Prabhat; Manik, Radheysham

2012-06-01

This study was aimed at establishing buffalo embryonic stem cells (ESCs) from in vitro fertilized (IVF), parthenogenetic, and hand-made cloned (HMC) embryos and to check their equivalency in terms of stem cell marker expression, longevity, proliferation, and differentiation pattern. ESCs derived from all three sources were found by immunofluorescence to express the pluripotency markers SSEA-4, TRA-1-60, TRA-1-81, OCT4, and SOX2 and were able to form embryoid bodies containing cells expressing genes specific to endoderm (AFP, HNF4, and GATA4), mesoderm (MSX1, BMP4, and ASA), and ectoderm (cytokeratin 8 and NF68). Reverse transcriptase PCR (RT-PCR) showed cells from all sources to be positive for pluripotency markers OCT4, SOX2, NANOG, STAT3, REX1, FOXD3, NUCLEOSTEMIN, and TELOMERASE. Pluripotency markers OCT4, SOX2, NANOG, and c-MYC were also analyzed by real-time PCR. No significant differences were observed among ESCs from all three sources for all these genes except NANOG, whose expression was higher (p<0.05) in HMC-derived ESCs (6.897±2.3) compared to that in parthenogenesis- and IVF-derived cells (1.603±0.315 and 1±0, respectively). Pluripotent, stable buffalo ESC lines derived from IVF, parthenogenesis, and HMC embryos may be genetically manipulated to provide a powerful tool for studies involving embryonic development, genomic imprinting, gene targeting, cloning, chimera formation, and transgenic animal production.

Differential tissue growth and cell adhesion alone drive early tooth morphogenesis: An ex vivo and in silico study

PubMed Central

Savriama, Yoland; Jernvall, Jukka

2018-01-01

From gastrulation to late organogenesis animal development involves many genetic and bio-mechanical interactions between epithelial and mesenchymal tissues. Ectodermal organs, such as hairs, feathers and teeth are well studied examples of organs whose development is based on epithelial-mesenchymal interactions. These develop from a similar primordium through an epithelial folding and its interaction with the mesenchyme. Despite extensive knowledge on the molecular pathways involved, little is known about the role of bio-mechanical processes in the morphogenesis of these organs. We propose a simple computational model for the biomechanics of one such organ, the tooth, and contrast its predictions against cell-tracking experiments, mechanical relaxation experiments and the observed tooth shape changes over developmental time. We found that two biomechanical processes, differential tissue growth and differential cell adhesion, were enough, in the model, for the development of the 3D morphology of the early tooth germ. This was largely determined by the length and direction of growth of the cervical loops, lateral folds of the enamel epithelium. The formation of these cervical loops was found to require accelerated epithelial growth relative to other tissues and their direction of growth depended on specific differential adhesion between the three tooth tissues. These two processes and geometrical constraints in early tooth bud also explained the shape asymmetry between the lateral cervical loops and those forming in the anterior and posterior of the tooth. By performing mechanical perturbations ex vivo and in silico we inferred the distribution and direction of tensile stresses in the mesenchyme that restricted cervical loop lateral growth and forced them to grow downwards. Overall our study suggests detailed quantitative explanations for how bio-mechanical processes lead to specific morphological 3D changes over developmental time. PMID:29481561

Cell delamination in the mesencephalic neural fold and its implication for the origin of ectomesenchyme

PubMed Central

Lee, Raymond Teck Ho; Nagai, Hiroki; Nakaya, Yukiko; Sheng, Guojun; Trainor, Paul A.; Weston, James A.; Thiery, Jean Paul

2013-01-01

The neural crest is a transient structure unique to vertebrate embryos that gives rise to multiple lineages along the rostrocaudal axis. In cranial regions, neural crest cells are thought to differentiate into chondrocytes, osteocytes, pericytes and stromal cells, which are collectively termed ectomesenchyme derivatives, as well as pigment and neuronal derivatives. There is still no consensus as to whether the neural crest can be classified as a homogenous multipotent population of cells. This unresolved controversy has important implications for the formation of ectomesenchyme and for confirmation of whether the neural fold is compartmentalized into distinct domains, each with a different repertoire of derivatives. Here we report in mouse and chicken that cells in the neural fold delaminate over an extended period from different regions of the cranial neural fold to give rise to cells with distinct fates. Importantly, cells that give rise to ectomesenchyme undergo epithelial-mesenchymal transition from a lateral neural fold domain that does not express definitive neural markers, such as Sox1 and N-cadherin. Additionally, the inference that cells originating from the cranial neural ectoderm have a common origin and cell fate with trunk neural crest cells prompted us to revisit the issue of what defines the neural crest and the origin of the ectomesenchyme. PMID:24198279

Derivation and characterisation of the human embryonic stem cell lines, NOTT1 and NOTT2.

PubMed

Priddle, Helen; Allegrucci, Cinzia; Burridge, Paul; Munoz, Maria; Smith, Nigel M; Devlin, Lyndsey; Sjoblom, Cecilia; Chamberlain, Sarah; Watson, Sue; Young, Lorraine E; Denning, Chris

2010-04-01

The ability to maintain human embryonic stem cells (hESCs) during long-term culture and yet induce differentiation to multiple lineages potentially provides a novel approach to address various biomedical problems. Here, we describe derivation of hESC lines, NOTT1 and NOTT2, from human blastocysts graded as 3BC and 3CB, respectively. Both lines were successfully maintained as colonies by mechanical passaging on mouse embryonic feeder cells or as monolayers by trypsin-passaging in feeder-free conditions on Matrigel. Undifferentiated cells retained expression of pluripotency markers (OCT4, NANOG, SSEA-4, TRA-1-60 and TRA-1-81), a stable karyotype during long-term culture and could be transfected efficiently with plasmid DNA and short interfering RNA. Differentiation via formation of embryoid bodies resulted in expression of genes associated with early germ layers and terminal lineage specification. The electrophysiology of spontaneously beating NOTT1-derived cardiomyocytes was recorded and these cells were shown to be pharmacologically responsive. Histological examination of teratomas formed by in vivo differentiation of both lines in severe immunocompromised mice showed complex structures including cartilage or smooth muscle (mesoderm), luminal epithelium (endoderm) and neuroectoderm (ectoderm). These observations show that NOTT1 and NOTT2 display the accepted characteristics of hESC pluripotency.

Histone posttranslational modifications and cell fate determination: lens induction requires the lysine acetyltransferases CBP and p300

PubMed Central

Wolf, Louise; Harrison, Wilbur; Huang, Jie; Xie, Qing; Xiao, Ningna; Sun, Jian; Kong, Lingkun; Lachke, Salil A.; Kuracha, Murali R.; Govindarajan, Venkatesh; Brindle, Paul K.; Ashery-Padan, Ruth; Beebe, David C.; Overbeek, Paul A.; Cvekl, Ales

2013-01-01

Lens induction is a classical embryologic model to study cell fate determination. It has been proposed earlier that specific changes in core histone modifications accompany the process of cell fate specification and determination. The lysine acetyltransferases CBP and p300 function as principal enzymes that modify core histones to facilitate specific gene expression. Herein, we performed conditional inactivation of both CBP and p300 in the ectodermal cells that give rise to the lens placode. Inactivation of both CBP and p300 resulted in the dramatic discontinuation of all aspects of lens specification and organogenesis, resulting in aphakia. The CBP/p300−/− ectodermal cells are viable and not prone to apoptosis. These cells showed reduced expression of Six3 and Sox2, while expression of Pax6 was not upregulated, indicating discontinuation of lens induction. Consequently, expression of αB- and αA-crystallins was not initiated. Mutant ectoderm exhibited markedly reduced levels of histone H3 K18 and K27 acetylation, subtly increased H3 K27me3 and unaltered overall levels of H3 K9ac and H3 K4me3. Our data demonstrate that CBP and p300 are required to establish lens cell-type identity during lens induction, and suggest that posttranslational histone modifications are integral to normal cell fate determination in the mammalian lens. PMID:24038357

Novel EDA mutation in X-linked hypohidrotic ectodermal dysplasia and genotype-phenotype correlation.

PubMed

Zeng, B; Lu, H; Xiao, X; Zhou, L; Lu, J; Zhu, L; Yu, D; Zhao, W

2015-11-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormalities of hair, teeth, and sweat glands, while non-syndromic hypodontia (NSH) affects only teeth. Mutations in Ectodysplasin A (EDA) underlie both XLHED and NSH. This study investigated the genetic causes of six hypohidrotic ectodermal dysplasia (HED) patients and genotype-phenotype correlation. The EDA gene of six patients with HED was sequenced. Bioinformatics analysis and structural modeling for the mutations were performed. The records of 134 patients with XLHED and EDA-related NSH regarding numbers of missing permanent teeth from this study and 20 articles were reviewed. Nonparametric tests were used to analyze genotype-phenotype correlations. In four of the six patients, we identified a novel mutation c.852T>G (p.Phe284Leu) and three reported mutations: c.467G>A (p.Arg156His), c.776C>A (p.Ala259Glu), and c.871G>A (p.Gly291Arg). They were predicted to be pathogenic by bioinformatics analysis and structural modeling. Genotype-phenotype correlation analysis revealed that truncating mutations were associated with more missing teeth. Missense mutations and the mutations affecting the TNF homology domain were correlated with fewer missing teeth. This study extended the mutation spectrum of XLHED and revealed the relationship between genotype and the number of missing permanent teeth. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A novel mutation in homeobox DNA binding domain of HOXC13 gene underlies pure hair and nail ectodermal dysplasia (ECTD9) in a Pakistani family.

PubMed

Khan, Anwar Kamal; Muhammad, Noor; Aziz, Abdul; Khan, Sher Alam; Shah, Khadim; Nasir, Abdul; Khan, Muzammil Ahmad; Khan, Saadullah

2017-04-12

Pure hair and nail ectodermal dysplasia (PHNED) is a congenital disorder of hair abnormalities and nail dysplasia. Both autosomal recessive and dominant inheritance fashion of PHNED occurs. In literature, to date, five different forms of PHNED have been reported at molecular level, having three genes known and two loci with no gene yet. In this study, a four generations consanguineous family of Pakistani origin with autosomal recessive PHNED was investigated. Affected members exhibited PHNED phenotypes with involvement of complete hair loss and nail dysplasia. To screen for mutation in the genes (HOXC13, KRT74, KRT85), its coding exons and exons-intron boundaries were sequenced. The 3D models of normal and mutated HOXC13 were predicted by using homology modeling. Through investigating the family to known loci, the family was mapped to ectodermal dysplasia 9 (ECTD9) loci with genetic address of 12q13.13. Mutation screening revealed a novel missense mutation (c.929A > C; p.Asn310Thr) in homeobox DNA binding domain of HOXC13 gene in affected members of the family. Due to mutation, loss of hydrogen bonding and difference in potential energy occurs, which may resulting in alteration of protein function. This is the first mutation reported in homeodomain, while 5 th mutation reported in HOXC13 gene causing PHNED.

Clinical outcomes of implant therapy in ectodermal dysplasia patients: a systematic review.

PubMed

Wang, Y; He, J; Decker, A M; Hu, J C; Zou, D

2016-08-01

The purpose of this review was to determine the outcome of oral function reconstruction in ectodermal dysplasia (ED) patients who have received dental implant therapy. A search was made of the PubMed and Web of Science databases; key words used were "(ectodermal dysplasia) AND (implant OR implants)", with supplementary retrieval key words "dental implant", "zygomatic implant", "anodontia", and "edentulous". Patient age, use of bone graft, implant site, type of implant, and survival rate of the implants were included in the subsequent data analysis. Forty-five articles published between 1988 and October 2015 were included in this analysis. The cases of a total of 96 patients were retrieved (22 children and 74 adults); these patients received a total of 701 implants. Fourteen implants were removed during a median follow-up time of 24 months. The 24-month implant survival rate was 97.9% in adult subjects and 98.6% in children. Sixty-eight percent of adult patients underwent bone augmentation prior to implant placement. Based on this review, dental implants are commonly used in the oral reconstruction of ED patients. However, long-term data on bone augmentation and implant success are needed, as well as additional clinical evidence on bone resorption, the esthetic outcomes of implant therapy, and physiological considerations in ED patients. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Wnt ligands from the embryonic surface ectoderm regulate ‘bimetallic strip’ optic cup morphogenesis in mouse

PubMed Central

Carpenter, April C.; Smith, April N.; Wagner, Heidi; Cohen-Tayar, Yamit; Rao, Sujata; Wallace, Valerie; Ashery-Padan, Ruth; Lang, Richard A.

2015-01-01

The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the surface ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wlsfl/fl) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated by RA or by the Wnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the surface ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium (RPE) progenitors near the optic cup rim. In Le-cre; Wlsfl/fl mice, the numbers of RPE cells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change. PMID:25715397

Development, Characterization, and Pluripotency Analysis of Buffalo (Bubalus bubalis) Embryonic Stem Cell Lines Derived from In Vitro–Fertilized, Hand-Guided Cloned, and Parthenogenetic Embryos

PubMed Central

Shah, Syed Mohmad; Saini, Neha; Ashraf, Syma; Zandi, Mohammad; Manik, Radhey Sham; Singla, Suresh Kumar; Palta, Prabhat

2015-01-01

Abstract We present the derivation, characterization, and pluripotency analysis of three buffalo embryonic stem cell (buESC) lines, from in vitro–fertilized, somatic cell nuclear–transferred, and parthenogenetic blastocysts. These cell lines were developed for later differentiation into germ lineage cells and elucidation of the signaling pathways involved. The cell lines were established from inner cell masses (ICMs) that were isolated manually from the in vitro–produced blastocysts. Most of the ICMs (45–55%) resulted in formation of primary colonies that were subcultured after 8–10 days, leading subsequently to the formation of three buESC lines, one from each blastocyst type. All the cell lines expressed stem cell markers, such as Alkaline Phosphatase, OCT4, NANOG, SSEA1, SSEA4, TRA-1-60, TRA-1-81, SOX2, REX1, CD-90, STAT3, and TELOMERASE. They differentiated into all three germ layers as determined by ectodermal, mesodermal, and endodermal RNA and protein markers. All of the cell lines showed equal expression of pluripotency markers as well as equivalent differentiation potential into all the three germ layers. The static suspension culture–derived embryoid bodies (EBs) showed greater expression of all the three germ layer markers as compared to hanging drop culture–derived EBs. When analyzed for germ layer marker expression, EBs derived from 15% fetal bovine serum (FBS)-based spontaneous differentiation medium showed greater differentiation across all the three germ layers as compared to those derived from Knock-Out Serum Replacement (KoSR)-based differentiation medium. PMID:26168169

Ectodermal dysplasia

MedlinePlus

... fever, because the skin cannot sweat and control temperature properly. Affected adults are unable to tolerate a ... need special measures to keep a normal body temperature. Depending on which genes are affected, other symptoms ...

The effect of diabetes on the wound healing potential of adipose-tissue derived stem cells.

PubMed

Kim, Sue Min; Kim, Yun Ho; Jun, Young Joon; Yoo, Gyeol; Rhie, Jong Won

2016-03-01

To investigate whether diabetes mellitus affects the wound-healing-promoting potential of adipose tissue-derived stem cells, we designed a wound-healing model using diabetic mice. We compared the degree of wound healing between wounds treated with normal adipose tissue-derived stem cells and wounds treated with diabetic adipose tissue-derived stem cells. We evaluated the wound-healing rate, the epithelial tongue distance, the area of granulation tissue, the number of capillary and the number of Ki-67-stained cells. The wound-healing rate was significantly higher in the normal adipose tissue-derived stem cells group than in the diabetic adipose tissue-derived stem cells group; it was also significantly higher in the normal adipose tissue-derived stem cells group than in the control group. Although the diabetic adipose tissue-derived stem cells group showed a better wound-healing rate than the control group, the difference was not statistically significant. Similar trends were observed for the other parameters examined: re-epithelisation and keratinocyte proliferation; granulation tissue formation; and dermal regeneration. However, with regard to the number of capillary, diabetic adipose tissue-derived stem cells retained their ability to promote neovasculisation and angiogenesis. These results reflect the general impairment of the therapeutic potential of diabetic adipose tissue-derived stem cells in vivo. © 2016 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Bioelectric signalling via potassium channels: a mechanism for craniofacial dysmorphogenesis in KCNJ2‐associated Andersen–Tawil Syndrome

PubMed Central

Adams, Dany Spencer; Uzel, Sebastien G. M.; Akagi, Jin; Wlodkowic, Donald; Andreeva, Viktoria; Yelick, Pamela Crotty; Devitt‐Lee, Adrian; Pare, Jean‐Francois; Levin, Michael

2016-01-01

Key points Xenopus laevis craniofacial development is a good system for the study of Andersen–Tawil Syndrome (ATS)‐associated craniofacial anomalies (CFAs) because (1) Kcnj2 is expressed in the nascent face; (2) molecular‐genetic and biophysical techniques are available for the study of ion‐dependent signalling during craniofacial morphogenesis; (3) as in humans, expression of variant Kcnj2 forms in embryos causes a muscle phenotype; and (4) variant forms of Kcnj2 found in human patients, when injected into frog embryos, cause CFAs in the same cell lineages.Forced expression of WT or variant Kcnj2 changes the normal pattern of V mem (resting potential) regionalization found in the ectoderm of neurulating embryos, and changes the normal pattern of expression of ten different genetic regulators of craniofacial development, including markers of cranial neural crest and of placodes.Expression of other potassium channels and two different light‐activated channels, all of which have an effect on V mem, causes CFAs like those induced by injection of Kcnj2 variants. In contrast, expression of Slc9A (NHE3), an electroneutral ion channel, and of GlyR, an inactive Cl− channel, do not cause CFAs, demonstrating that correct craniofacial development depends on a pattern of bioelectric states, not on ion‐ or channel‐specific signalling.Using optogenetics to control both the location and the timing of ion flux in developing embryos, we show that affecting V mem of the ectoderm and no other cell layers is sufficient to cause CFAs, but only during early neurula stages. Changes in V mem induced late in neurulation do not affect craniofacial development.We interpret these data as strong evidence, consistent with our hypothesis, that ATS‐associated CFAs are caused by the effect of variant Kcnj2 on the V mem of ectodermal cells of the developing face. We predict that the critical time is early during neurulation, and the critical cells are the ectodermal cranial neural crest and placode lineages. This points to the potential utility of extant, ion flux‐modifying drugs as treatments to prevent CFAs associated with channelopathies such as ATS. Abstract Variants in potassium channel KCNJ2 cause Andersen–Tawil Syndrome (ATS); the induced craniofacial anomalies (CFAs) are entirely unexplained. We show that KCNJ2 is expressed in Xenopus and mouse during the earliest stages of craniofacial development. Misexpression in Xenopus of KCNJ2 carrying ATS‐associated mutations causes CFAs in the same structures affected in humans, changes the normal pattern of membrane voltage potential regionalization in the developing face and disrupts expression of important craniofacial patterning genes, revealing the endogenous control of craniofacial patterning by bioelectric cell states. By altering cells’ resting potentials using other ion translocators, we show that a change in ectodermal voltage, not tied to a specific protein or ion, is sufficient to cause CFAs. By adapting optogenetics for use in non‐neural cells in embryos, we show that developmentally patterned K+ flux is required for correct regionalization of the resting potentials and for establishment of endogenous early gene expression domains in the anterior ectoderm, and that variants in KCNJ2 disrupt this regionalization, leading to the CFAs seen in ATS patients. PMID:26864374

Hair organ regeneration via the bioengineered hair follicular unit transplantation

PubMed Central

Asakawa, Kyosuke; Toyoshima, Koh-ei; Ishibashi, Naoko; Tobe, Hirofumi; Iwadate, Ayako; Kanayama, Tatsuya; Hasegawa, Tomoko; Nakao, Kazuhisa; Toki, Hiroshi; Noguchi, Shotaro; Ogawa, Miho; Sato, Akio; Tsuji, Takashi

2012-01-01

Organ regenerative therapy aims to reproduce fully functional organs to replace organs that have been lost or damaged as a result of disease, injury, or aging. For the fully functional regeneration of ectodermal organs, a concept has been proposed in which a bioengineered organ is developed by reproducing the embryonic processes of organogenesis. Here, we show that a bioengineered hair follicle germ, which was reconstituted with embryonic skin-derived epithelial and mesenchymal cells and ectopically transplanted, was able to develop histologically correct hair follicles. The bioengineered hair follicles properly connected to the host skin epithelium by intracutaneous transplantation and reproduced the stem cell niche and hair cycles. The bioengineered hair follicles also autonomously connected with nerves and the arrector pili muscle at the permanent region and exhibited piloerection ability. Our findings indicate that the bioengineered hair follicles could restore physiological hair functions and could be applicable to surgical treatments for alopecia. PMID:22645640

Regional differences in the expression of laminin isoforms during mouse neural tube development

PubMed Central

Copp, Andrew J.; Carvalho, Rita; Wallace, Adam; Sorokin, Lydia; Sasaki, Takako; Greene, Nicholas D.E.; Ybot-Gonzalez, Patricia

2013-01-01

Many significant human birth defects originate around the time of neural tube closure or early during post-closure nervous system development. For example, failure of the neural tube to close generates anencephaly and spina bifida, faulty cell cycle progression is implicated in primary microcephaly, while defective migration of neuroblasts can lead to neuronal migration disorders such as lissencephaly. At the stage of neural tube closure, basement membranes are becoming organised around the neuroepithelium, and beneath the adjacent non-neural surface ectoderm. While there is circumstantial evidence to implicate basement membrane dynamics in neural tube and surface ectodermal development, we have an incomplete understanding of the molecular composition of basement membranes at this stage. In the present study, we examined the developing basement membranes of the mouse embryo at mid-gestation (embryonic day 9.5), with particular reference to laminin composition. We performed in situ hybridization to detect the mRNAs of all eleven individual laminin chains, and immunohistochemistry to identify which laminin chains are present in the basement membranes. From this information, we inferred the likely laminin variants and their tissues of origin: that is, whether a given basement membrane laminin is contributed by epithelium, mesenchyme, or both. Our findings reveal major differences in basement composition along the body axis, with the rostral neural tube (at mandibular arch and heart levels) exhibiting many distinct laminin variants, while the lumbar level where the neural tube is just closing shows a much simpler laminin profile. Moreover, there appears to be a marked difference in the extent to which the mesenchyme contributes laminin variants to the basement membrane, with potential contribution of several laminins rostrally, but no contribution caudally. This information paves the way towards a mechanistic analysis of basement membrane laminin function during early neural tube development in mammals. PMID:21524702

Deciphering the Genetic Programme Triggering Timely and Spatially-Regulated Chitin Deposition

PubMed Central

Rotstein, Bárbara; Casali, Andreu; Llimargas, Marta

2015-01-01

Organ and tissue formation requires a finely tuned temporal and spatial regulation of differentiation programmes. This is necessary to balance sufficient plasticity to undergo morphogenesis with the acquisition of the mature traits needed for physiological activity. Here we addressed this issue by analysing the deposition of the chitinous extracellular matrix of Drosophila, an essential element of the cuticle (skin) and respiratory system (tracheae) in this insect. Chitin deposition requires the activity of the chitin synthase Krotzkopf verkehrt (Kkv). Our data demonstrate that this process equally requires the activity of two other genes, namely expansion (exp) and rebuf (reb). We found that Exp and Reb have interchangeable functions, and in their absence no chitin is produced, in spite of the presence of Kkv. Conversely, when Kkv and Exp/Reb are co-expressed in the ectoderm, they promote chitin deposition, even in tissues normally devoid of this polysaccharide. Therefore, our results indicate that both functions are not only required but also sufficient to trigger chitin accumulation. We show that this mechanism is highly regulated in time and space, ensuring chitin accumulation in the correct tissues and developmental stages. Accordingly, we observed that unregulated chitin deposition disturbs morphogenesis, thus highlighting the need for tight regulation of this process. In summary, here we identify the genetic programme that triggers the timely and spatially regulated deposition of chitin and thus provide new insights into the extracellular matrix maturation required for physiological activity. PMID:25617778

Ectodermal Influx and Cell Hypertrophy Provide Early Growth for All Murine Mammary Rudiments, and Are Differentially Regulated among Them by Gli3

PubMed Central

Lee, May Yin; Racine, Victor; Jagadpramana, Peter; Sun, Li; Yu, Weimiao; Du, Tiehua; Spencer-Dene, Bradley; Rubin, Nicole; Le, Lendy; Ndiaye, Delphine; Bellusci, Saverio; Kratochwil, Klaus; Veltmaat, Jacqueline M.

2011-01-01

Mammary gland development starts in utero with one or several pairs of mammary rudiments (MRs) budding from the surface ectodermal component of the mammalian embryonic skin. Mice develop five pairs, numbered MR1 to MR5 from pectoral to inguinal position. We have previously shown that Gli3Xt-J/Xt-J mutant embryos, which lack the transcription factor Gli3, do not form MR3 and MR5. We show here that two days after the MRs emerge, Gli3Xt-J/Xt-J MR1 is 20% smaller, and Gli3Xt-J/Xt-J MR2 and MR4 are 50% smaller than their wild type (wt) counterparts. Moreover, while wt MRs sink into the underlying dermis, Gli3Xt-J/Xt-J MR4 and MR2 protrude outwardly, to different extents. To understand why each of these five pairs of functionally identical organs has its own, distinct response to the absence of Gli3, we determined which cellular mechanisms regulate growth of the individual MRs, and whether and how Gli3 regulates these mechanisms. We found a 5.5 to 10.7-fold lower cell proliferation rate in wt MRs compared to their adjacent surface ectoderm, indicating that MRs do not emerge or grow via locally enhanced cell proliferation. Cell-tracing experiments showed that surface ectodermal cells are recruited toward the positions where MRs emerge, and contribute to MR growth during at least two days. During the second day of MR development, peripheral cells within the MRs undergo hypertrophy, which also contributes to MR growth. Limited apoptotic cell death counterbalances MR growth. The relative contribution of each of these processes varies among the five MRs. Furthermore, each of these processes is impaired in the absence of Gli3, but to different extents in each MR. This differential involvement of Gli3 explains the variation in phenotype among Gli3Xt-J/Xt-J MRs, and may help to understand the variation in numbers and positions of mammary glands among mammals. PMID:22046263

Epithelial Cell Rests of Malassez Contain Unique Stem Cell Populations Capable of Undergoing Epithelial–Mesenchymal Transition

PubMed Central

Xiong, Jimin; Mrozik, Krzysztof; Gronthos, Stan

2012-01-01

The epithelial cell rests of Malassez (ERM) are odontogenic epithelial cells located within the periodontal ligament matrix. While their function is unknown, they may support tissue homeostasis and maintain periodontal ligament space or even contribute to periodontal regeneration. We investigated the notion that ERM contain a subpopulation of stem cells that could undergo epithelial–mesenchymal transition and differentiate into mesenchymal stem-like cells with multilineage potential. For this purpose, ERM collected from ovine incisors were subjected to different inductive conditions in vitro, previously developed for the characterization of bone marrow mesenchymal stromal/stem cells (BMSC). We found that ex vivo-expanded ERM expressed both epithelial (cytokeratin-8, E-cadherin, and epithelial membrane protein-1) and BMSC markers (CD44, CD29, and heat shock protein-90β). Integrin α6/CD49f could be used for the enrichment of clonogenic cell clusters [colony-forming units-epithelial cells (CFU-Epi)]. Integrin α6/CD49f-positive-selected epithelial cells demonstrated over 50- and 7-fold greater CFU-Epi than integrin α6/CD49f-negative cells and unfractionated cells, respectively. Importantly, ERM demonstrated stem cell-like properties in their differentiation capacity to form bone, fat, cartilage, and neural cells in vitro. When transplanted into immunocompromised mice, ERM generated bone, cementum-like and Sharpey's fiber-like structures. Additionally, gene expression studies showed that osteogenic induction of ERM triggered an epithelial–mesenchymal transition. In conclusion, ERM are unusual cells that display the morphological and phenotypic characteristics of ectoderm-derived epithelial cells; however, they also have the capacity to differentiate into a mesenchymal phenotype and thus represent a unique stem cell population within the periodontal ligament. PMID:22122577

Epithelial topography for repetitive tooth formation

PubMed Central

Gaete, Marcia; Fons, Juan Manuel; Popa, Elena Mădălina; Chatzeli, Lemonia; Tucker, Abigail S.

2015-01-01

ABSTRACT During the formation of repetitive ectodermally derived organs such as mammary glands, lateral line and teeth, the tissue primordium iteratively initiates new structures. In the case of successional molar development, new teeth appear sequentially in the posterior region of the jaw from Sox2+ cells in association with the posterior aspect of a pre-existing tooth. The sequence of molar development is well known, however, the epithelial topography involved in the formation of a new tooth is unclear. Here, we have examined the morphology of the molar dental epithelium and its development at different stages in the mouse in vivo and in molar explants. Using regional lineage tracing we show that within the posterior tail of the first molar the primordium for the second and third molar are organized in a row, with the tail remaining in connection with the surface, where a furrow is observed. The morphology and Sox2 expression of the tail retains characteristics reminiscent of the earlier stages of tooth development, such that position along the A-P axes of the tail correlates with different temporal stages. Sox9, a stem/progenitor cell marker in other organs, is expressed mainly in the suprabasal epithelium complementary with Sox2 expression. This Sox2 and Sox9 expressing molar tail contains actively proliferating cells with mitosis following an apico-basal direction. Snail2, a transcription factor implicated in cell migration, is expressed at high levels in the tip of the molar tail while E-cadherin and laminin are decreased. In conclusion, our studies propose a model in which the epithelium of the molar tail can grow by posterior movement of epithelial cells followed by infolding and stratification involving a population of Sox2+/Sox9+ cells. PMID:26538639

Salinity alters snakeskin and mesh transcript abundance and permeability in midgut and Malpighian tubules of larval mosquito, Aedes aegypti.

PubMed

Jonusaite, Sima; Donini, Andrew; Kelly, Scott P

2017-03-01

This study examined the distribution and localization of the septate junction (SJ) proteins snakeskin (Ssk) and mesh in osmoregulatory organs of larval mosquito (Aedes aegypti), as well as their response to altered environmental salt levels. Ssk and mesh transcripts and immunoreactivity were detected in tissues of endodermal origin such as the midgut and Malpighian tubules of A. aegypti larvae, but not in ectodermally derived hindgut and anal papillae. Immunolocalization of Ssk and mesh in the midgut and Malpighian tubules indicated that both proteins are concentrated at regions of cell-cell contact between epithelial cells. Transcript abundance of ssk and mesh was higher in the midgut and Malpighian tubules of brackish water (BW, 30% SW) reared A. aegypti larvae when compared with freshwater (FW) reared animals. Therefore, [ 3 H]polyethylene glycol (MW 400Da, PEG-400) flux was examined across isolated midgut and Malpighian tubule preparations as a measure of their paracellular permeability. It was found that PEG-400 flux was greater across the midgut of BW versus FW larvae while the Malpighian tubules of BW-reared larvae had reduced PEG-400 permeability in conjunction with increased Cl - secretion compared to FW animals. Taken together, data suggest that Ssk and mesh are found in smooth SJs (sSJs) of larval A. aegypti and that their abundance alters in association with changes in epithelial permeability when larvae reside in water of differing salt content. This latter observation suggests that Ssk and mesh play a role in the homeostatic control of salt and water balance in larval A. aegypti. Copyright © 2016 Elsevier Inc. All rights reserved.

Developmental abnormalities of the posterior pituitary gland.

PubMed

di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

2009-01-01

While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

cDNA cloning and characterization of mouse DTEF-1 and ETF, members of the TEA/ATTS family of transcription factors.

PubMed

Yockey, C E; Shimizu, N

1998-02-01

Members of the TEA/ATTS family of transcription factors have been found in most representative eukaryotic organisms. In vertebrates, the TEA family contains at least four members, which share overlapping DNA-binding specificity and have similar transcriptional activation properties. In this article, we describe the cDNA cloning and characterization of the murine TEA proteins DTEF-1 (mDTEF-1) and ETF. Using in situ hybridization analysis of mouse embryos, we found that mDTEF-1 and ETF transcript distributions substantially overlap. ETF is expressed throughout the embryo except in the myocardium early in development, whereas late in development, it is enriched in lung and neuroectoderm. Mouse DTEF-1 is expressed at a much lower level throughout development and is substantially enriched in ectoderm and skin, as well as in the developing pituitary at midgestation. Northern blot analysis of adult mouse tissue total RNA showed that both ETF and mDTEF-1 are abundant in uterus and lung relative to other tissues. Using gel mobility shift assays and GAL4-fusion protein analysis, we demonstrated that the full coding sequences of ETF and mDTEF-1 encode M-CAT/GT-IIC-binding proteins containing activation domains.

A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra

PubMed Central

Glauber, Kristine M.; Dana, Catherine E.; Park, Steve S.; Colby, David A.; Noro, Yukihiko; Fujisawa, Toshitaka; Chamberlin, A. Richard; Steele, Robert E.

2013-01-01

Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes. PMID:24255098

A small molecule screen identifies a novel compound that induces a homeotic transformation in Hydra.

PubMed

Glauber, Kristine M; Dana, Catherine E; Park, Steve S; Colby, David A; Noro, Yukihiko; Fujisawa, Toshitaka; Chamberlin, A Richard; Steele, Robert E

2013-12-01

Developmental processes such as morphogenesis, patterning and differentiation are continuously active in the adult Hydra polyp. We carried out a small molecule screen to identify compounds that affect patterning in Hydra. We identified a novel molecule, DAC-2-25, that causes a homeotic transformation of body column into tentacle zone. This transformation occurs in a progressive and polar fashion, beginning at the oral end of the animal. We have identified several strains that respond to DAC-2-25 and one that does not, and we used chimeras from these strains to identify the ectoderm as the target tissue for DAC-2-25. Using transgenic Hydra that express green fluorescent protein under the control of relevant promoters, we examined how DAC-2-25 affects tentacle patterning. Genes whose expression is associated with the tentacle zone are ectopically expressed upon exposure to DAC-2-25, whereas those associated with body column tissue are turned off as the tentacle zone expands. The expression patterns of the organizer-associated gene HyWnt3 and the hypostome-specific gene HyBra2 are unchanged. Structure-activity relationship studies have identified features of DAC-2-25 that are required for activity and potency. This study shows that small molecule screens in Hydra can be used to dissect patterning processes.

Genetics Home Reference: hypohidrotic ectodermal dysplasia

MedlinePlus

... chromosome , one of the two sex chromosomes . In males (who have only one X chromosome ), one altered ... copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much ...

Expression of Wise in chick embryos.

PubMed

Shigetani, Y; Itasaki, N

2007-08-01

We have performed in situ hybridization to study the expression of Wise in early chick embryos. Wise expression is first detectable in the ectoderm at posterior levels of late neurula. As development proceeds, Wise expression is seen in specific patterns in the ectoderm of the trunk region, pharyngeal arches, limb buds, and feather buds. In addition to these areas, particular cartilages such as the ones in the maxillary process and limbs start to express Wise at the late pharyngula stage, and the expression in these cartilages becomes stronger than that in epidermal components at later stages. Importantly, Wise is expressed in regions where other signaling molecules such as Wnt, Bmp, and Shh are known to function in morphogenesis and differentiation. Direct comparisons of the expression of Wise and these genes are also demonstrated. (c) 2007 Wiley-Liss, Inc.

Patterning of mammalian somites by surface ectoderm and notochord: evidence for sclerotome induction by a hedgehog homolog.

PubMed

Fan, C M; Tessier-Lavigne, M

1994-12-30

An early step in the development of vertebrae, ribs, muscle, and dermis is the differentiation of the somitic mesoderm into dermomyotome dorsally and sclerotome ventrally. To analyze this process, we have developed an in vitro assay for somitic mesoderm differentiation. We show that sclerotomal markers can be induced by a diffusible factor secreted by notochord and floor plate and that heterologous cells expressing Sonic hedgehog (shh/vhh-1) mimic this effect. In contrast, expression of dermomyotomal markers can be caused by a contact-dependent signal from surface ectoderm and a diffusible signal from dorsal neural tube. Our results extend previous studies by suggesting that dorsoventral patterning of somites involves the coordinate action of multiple dorsalizing and ventralizing signals and that a diffusible form of Shh/Vhh-1 mediates sclerotome induction.

p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion*

PubMed Central

Greenblatt, Matthew B.; Kim, Jung-Min; Oh, Hwanhee; Park, Kwang Hwan; Choo, Min-Kyung; Sano, Yasuyo; Tye, Coralee E.; Skobe, Ziedonis; Davis, Roger J.; Park, Jin Mo; Bei, Marianna; Glimcher, Laurie H.; Shim, Jae-Hyuck

2015-01-01

An improved understanding of the molecular pathways that drive tooth morphogenesis and enamel secretion is needed to generate teeth from organ cultures for therapeutic implantation or to determine the pathogenesis of primary disorders of dentition (Abdollah, S., Macias-Silva, M., Tsukazaki, T., Hayashi, H., Attisano, L., and Wrana, J. L. (1997) J. Biol. Chem. 272, 27678–27685). Here we present a novel ectodermal dysplasia phenotype associated with conditional deletion of p38α MAPK in ectodermal appendages using K14-cre mice (p38αK14 mice). These mice display impaired patterning of dental cusps and a profound defect in the production and biomechanical strength of dental enamel because of defects in ameloblast differentiation and activity. In the absence of p38α, expression of amelogenin and β4-integrin in ameloblasts and p21 in the enamel knot was significantly reduced. Mice lacking the MAP2K MKK6, but not mice lacking MAP2K MKK3, also show the enamel defects, implying that MKK6 functions as an upstream kinase of p38α in ectodermal appendages. Lastly, stimulation with BMP2/7 in both explant culture and an ameloblast cell line confirm that p38α functions downstream of BMPs in this context. Thus, BMP-induced activation of the p38α MAPK pathway is critical for the morphogenesis of tooth cusps and the secretion of dental enamel. PMID:25406311

FGF signaling induces mesoderm in the hemichordate Saccoglossus kowalevskii

PubMed Central

Green, Stephen A.; Norris, Rachael P.; Terasaki, Mark; Lowe, Christopher J.

2013-01-01

FGFs act in vertebrate mesoderm induction and also play key roles in early mesoderm formation in ascidians and amphioxus. However, in sea urchins initial characterizations of FGF function do not support a role in early mesoderm induction, making the ancestral roles of FGF signaling and mechanisms of mesoderm specification in deuterostomes unclear. In order to better characterize the evolution of mesoderm formation, we have examined the role of FGF signaling during mesoderm development in Saccoglossus kowalevskii, an experimentally tractable representative of hemichordates. We report the expression of an FGF ligand, fgf8/17/18, in ectoderm overlying sites of mesoderm specification within the archenteron endomesoderm. Embryological experiments demonstrate that mesoderm induction in the archenteron requires contact with ectoderm, and loss-of-function experiments indicate that both FGF ligand and receptor are necessary for mesoderm specification. fgf8/17/18 gain-of-function experiments establish that FGF8/17/18 is sufficient to induce mesoderm in adjacent endomesoderm. These experiments suggest that FGF signaling is necessary from the earliest stages of mesoderm specification and is required for all mesoderm development. Furthermore, they suggest that the archenteron is competent to form mesoderm or endoderm, and that FGF signaling from the ectoderm defines the location and amount of mesoderm. When considered in a comparative context, these data support a phylogenetically broad requirement for FGF8/17/18 signaling in mesoderm specification and suggest that FGF signaling played an ancestral role in deuterostome mesoderm formation. PMID:23344709

The development of the eyelids. Part I. External features.

PubMed Central

Pearson, A A

1980-01-01

The sequence of developmental events leading to the formation of the eyelids is described in staged human embryos. By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode (Stage 13). A few days later (about 32 days, Stage 14) the lens placode is indented by the lens pit. A day or two later (about 33 days, Stage 15) the lens pit is closed: however, the lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it (stage 16, 37 days). As these grooves deepen, in Stages 17--19, eyelid folds develop, first below, and then above, the eye. In Stages 19--22 the eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19. The inner canthus is established a few days later in Stage 20. Closure of the eyelids is complete in Stage 23. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 PMID:7364662

Scanning Electron Microscopic Hair Shaft Analysis in Ectodermal Dysplasia Syndromes.

PubMed

Hirano-Ali, Stefanie A; Reed, Ashley M; Rowan, Brandon J; Sorrells, Timothy; Williams, Judith V; Pariser, David M; Hood, Antoinette F; Salkey, Kimberly

2015-01-01

The objective of the current study was to catalog hair shaft abnormalities in individuals with ectodermal dysplasia (ED) syndromes using scanning electron microscopy (SEM) and to compare the findings with those in unaffected controls. This is the second of a two-part study, the first of which used light microscopy as the modality and was previously published. Scanning electron microscopy was performed in a blinded manner on hair shafts from 65 subjects with seven types of ED syndromes and 41 unaffected control subjects. Assessment was performed along the length of the shaft and in cross section. Hair donations were collected at the 28th Annual National Family Conference held by the National Foundation for Ectodermal Dysplasia. Control subjects were recruited from a private dermatology practice and an academic children's hospital outpatient dermatology clinic. SEM identified various pathologic hair shaft abnormalities in each type of ED and in control patients. When hairs with all types of ED were grouped together and compared with those of control patients, the difference in the presence of small diameter and shallow and deep grooves was statistically significant (p < 0.05). When the EDs were separated according to subtype, statistically significant findings were also seen. SEM is a possible adjuvant tool in the diagnosis of ED syndromes. There are significant differences, with high specificity, between the hairs of individuals with ED and those of control subjects and between subtypes. © 2015 Wiley Periodicals, Inc.

Eight Mutations of Three Genes (EDA, EDAR, and WNT10A) Identified in Seven Hypohidrotic Ectodermal Dysplasia Patients.

PubMed

Zeng, Binghui; Xiao, Xue; Li, Sijie; Lu, Hui; Lu, Jiaxuan; Zhu, Ling; Yu, Dongsheng; Zhao, Wei

2016-09-19

Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the teeth, hair, and sweat glands. Ectodysplasin A (EDA), Ectodysplasin A receptor (EDAR), and EDAR-associated death domain (EDARADD) are candidate genes for HED, but the relationship between WNT10A and HED has not yet been validated. In this study, we included patients who presented at least two of the three ectodermal dysplasia features. The four genes were analyzed in seven HED patients by PCR and Sanger sequencing. Five EDA and one EDAR heterozygous mutations were identified in families 1-6. Two WNT10A heterozygous mutations were identified in family 7 as a compound heterozygote. c.662G>A (p.Gly221Asp) in EDA and c.354T>G (p.Tyr118*) in WNT10A are novel mutations. Bioinformatics analyses results confirmed the pathogenicity of the two novel mutations. In family 7, we also identified two single-nucleotide polymorphisms (SNPs) that were predicted to affect the splicing of EDAR. Analysis of the patient's total RNA revealed normal splicing of EDAR. This ascertained that the compound heterozygous WNT10A mutations are the genetic defects that led to the onset of HED. Our data revealed the genetic basis of seven HED patients and expended the mutational spectrum. Interestingly, we confirmed WNT10A as a candidate gene of HED and we propose WNT10A to be tested in EDA-negative HED patients.

Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: A systematic review.

PubMed

Schnabl, D; Grunert, I; Schmuth, M; Kapferer-Seebacher, I

2018-04-21

Hypohidrotic ectodermal dysplasia (HED) comprises a large group of inherited disorders of ectodermal structures, characterised by hypo- or anhidrosis, hypotrichosis and hypo- or oligo- or anodontia. We aimed to systematically assess the spectrum of prosthodontic approaches with regard to the patients' age and to provide clinical implications for practicing dentists. An electronic and manual search was conducted in four databases (Medline, LIVIVO, Cochrane Library, Web of Science Core Collection). Publications of multiple study designs written in English or German without data restrictions, reporting on prosthodontic treatment of patients diagnosed with HED and afflicted with oligo- or anodontia, were included. In total, 75 articles on 146 patients were analysed according to the patients' age. In children aged 2-17 years, removable full or partial (over)dentures represented standard treatment. In the mandible, implant-supported removable dentures on two interforaminal implants presented an alternative, already in young childhood. In cases with more than six teeth per jaw, also fixed (resin) bridges were used, frequently after orthodontic treatment. In adults, fixed or removable reconstructions with the help of up to eight implants per jaw, usually placed after bone augmentation procedures, were standard. Ten case reports/series with long-term follow-up illustrated the need for consistent maintenance including denture renewals. Prosthodontic rehabilitation should start in early childhood and needs to be revised in accordance with the patients' growth. Treatment should be carried out by a multidisciplinary team addressing variable demands in different age groups. © 2018 John Wiley & Sons Ltd.

2008 International Conference on Ectodermal Dysplasias Classification Conference Report

PubMed Central

Salinas, Carlos F.; Jorgenson, Ronald J.; Wright, J. Timothy; DiGiovanna, John J.; Fete, Mary D.

2009-01-01

There are many ways to classify ectodermal dysplasia syndromes. Clinicians in practice use a list of syndromes from which to choose a potential diagnosis, paging through a volume, such as Freire-Maia and Pinheiro's corpus, matching their patient's findings to listed syndromes. Medical researchers may want a list of syndromes that share one (monothetic system) or several (polythetic system) traits in order to focus research on a narrowly defined group. Special interest groups may want a list from which they can choose constituencies, and insurance companies and government agencies may want a list to determine for whom to provide (or deny) health care coverage. Furthermore, various molecular biologists are now promoting classification systems based on gene mutation (e.g. TP63 associated syndromes) or common molecular pathways. The challenge will be to balance comprehensiveness within the classification with usability and accessibility so that the benefits truly serve the needs of researchers, health care providers and ultimately the individuals and families directly affected by ectodermal dysplasias. It is also recognized that a new classification approach is an ongoing process and will require periodical reviews or updates. Whatever scheme is developed, however, will have far-reaching application for other groups of disorders for which classification is complicated by the number of interested parties and advances in diagnostic acumen. Consensus among interested parties is necessary for optimizing communication among the diverse groups whether it be for equitable distribution of funds, correctness of diagnosis and treatment, or focusing research efforts. PMID:19681152

Regional neural tube closure defined by the Grainy head-like transcription factors.

PubMed

Rifat, Yeliz; Parekh, Vishwas; Wilanowski, Tomasz; Hislop, Nikki R; Auden, Alana; Ting, Stephen B; Cunningham, John M; Jane, Stephen M

2010-09-15

Primary neurulation in mammals has been defined by distinct anatomical closure sites, at the hindbrain/cervical spine (closure 1), forebrain/midbrain boundary (closure 2), and rostral end of the forebrain (closure 3). Zones of neurulation have also been characterized by morphologic differences in neural fold elevation, with non-neural ectoderm-induced formation of paired dorso-lateral hinge points (DLHP) essential for neural tube closure in the cranial and lower spinal cord regions, and notochord-induced bending at the median hinge point (MHP) sufficient for closure in the upper spinal region. Here we identify a unifying molecular basis for these observations based on the function of the non-neural ectoderm-specific Grainy head-like genes in mice. Using a gene-targeting approach we show that deletion of Grhl2 results in failed closure 3, with mutants exhibiting a split-face malformation and exencephaly, associated with failure of neuro-epithelial folding at the DLHP. Loss of Grhl3 alone defines a distinct lower spinal closure defect, also with defective DLHP formation. The two genes contribute equally to closure 2, where only Grhl gene dosage is limiting. Combined deletion of Grhl2 and Grhl3 induces severe rostral and caudal neural tube defects, but DLHP-independent closure 1 proceeds normally in the upper spinal region. These findings provide a molecular basis for non-neural ectoderm mediated formation of the DLHP that is critical for complete neuraxis closure. (c) 2010 Elsevier Inc. All rights reserved.

Wnt-dependent epithelial transitions drive pharyngeal pouch formation

PubMed Central

Choe, Chong Pyo; Collazo, Andres; Trinh, Le A.; Pan, Luyuan; Moens, Cecilia B.; Crump, J. Gage

2013-01-01

SUMMARY The pharyngeal pouches, which form by budding of the foregut endoderm, are essential for segmentation of the vertebrate face. To date, the cellular mechanism and segmental nature of such budding have remained elusive. Here, we find that Wnt11r and Wnt4a from the head mesoderm and ectoderm, respectively, play distinct roles in the segmental formation of pouches in zebrafish. Time-lapse microscopy, combined with mutant and tissue-specific transgenic experiments, reveal requirements of Wnt signaling in two phases of endodermal epithelial transitions. Initially, Wnt11r and Rac1 destabilize the endodermal epithelium to promote the lateral movement of pouch-forming cells. Next, Wnt4a and Cdc42 signaling induce the rearrangement of maturing pouch cells into bilayers through junctional localization of the Alcama immunoglobulin-domain protein, which functions to restabilize adherens junctions. We propose that this dynamic control of epithelial morphology by Wnt signaling may be a common theme for the budding of organ anlagen from the endoderm. PMID:23375584

FGF-mediated mesoderm induction involves the Src-family kinase Laloo.

PubMed

Weinstein, D C; Marden, J; Carnevali, F; Hemmati-Brivanlou, A

1998-08-27

During embryogenesis, inductive interactions underlie the development of much of the body plan. In Xenopus laevis, factors secreted from the vegetal pole induce mesoderm in the adjacent marginal zone; members of both the transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) ligand families seem to have critical roles in this process. Here we report the identification and characterization of laloo, a novel participant in the signal transduction cascade linking extracellular, mesoderm-inducing signals to the nucleus, where alteration of cell fate is driven by changes in gene expression. Overexpression of laloo, a member of the Src-related gene family, in Xenopus embryos gives rise to ectopic posterior structures that frequently contain axial tissue. Laloo induces mesoderm in Xenopus ectodermal explants; this induction is blocked by reagents that disrupt the FGF signalling pathway. Conversely, expression of a dominant-inhibitory Laloo mutant blocks mesoderm induction by FGF and causes severe posterior truncations in vivo. This work provides the first evidence that a Src-related kinase is involved in vertebrate mesoderm induction.

Autoreactive T Cells and Chronic Fungal Infection Drive Esophageal Carcinogenesis

PubMed Central

Zhu, Feng; Willette-Brown, Jami; Song, Na-Young; Lomada, Dakshayani; Song, Yongmei; Xue, Liyan; Gray, Zane; Zhao, Zitong; Davis, Sean R.; Sun, Zhonghe; Zhang, Peilin; Wu, Xiaolin; Zhan, Qimin; Richie, Ellen R.; Hu, Yinling

2018-01-01

SUMMARY Humans with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a T cell–driven autoimmune disease caused by impaired central tolerance, are susceptible to developing chronic fungal infection and esophageal squamous cell carcinoma (ESCC). However, the relationship between autoreactive T cells and chronic fungal infection in ESCC development remains unclear. We find that kinase-dead Ikkα knockin mice develop phenotypes reminiscent of APECED, including impaired central tolerance, autoreactive T cells, chronic fungal infection, and ESCCs expressing specific human ESCC markers. Using this model, we investigated the potential link between ESCC and fungal infection. Autoreactive CD4 T cells permit fungal infection and incite tissue injury and inflammation. Antifungal treatment or depletion of autoreactive CD4 T cells rescues, whereas oral fungal administration promotes, ESCC development. Inhibition of inflammation or EGFR activity decreases fungal burden. Importantly, fungal infection is highly associated with ESCCs in non-autoimmune human patients. Therefore, autoreactive T cells and chronic fungal infection, fostered by inflammation and epithelial injury, promote ESCC development. PMID:28407484

The G-protein-coupled receptor, GPR84, is important for eye development in Xenopus laevis.

PubMed

Perry, Kimberly J; Johnson, Verity R; Malloch, Erica L; Fukui, Lisa; Wever, Jason; Thomas, Alvin G; Hamilton, Paul W; Henry, Jonathan J

2010-11-01

G-protein-coupled receptors (GPCRs) represent diverse, multifamily groups of cell signaling receptors involved in many cellular processes. We identified Xenopus laevis GPR84 as a member of the A18 subfamily of GPCRs. During development, GPR84 is detected in the embryonic lens placode, differentiating lens fiber cells, retina, and cornea. Anti-sense morpholino oligonucleotide-mediated knockdown and RNA rescue experiments demonstrate GPR84's importance in lens, cornea, and retinal development. Examination of cell proliferation using an antibody against histone H3 S10P reveals significant increases in the lens and retina following GPR84 knockdown. Additionally, there was also an increase in apoptosis in the retina and lens, as revealed by TUNEL assay. Reciprocal transplantation of the presumptive lens ectoderm between uninjected controls and morpholino-injected embryos demonstrates that GPR84 is necessary in the retina for proper development of the retina, as well as other eye tissues including the lens and cornea. © 2010 Wiley-Liss, Inc.

The G-protein-coupled receptor, GPR84, is important for eye development in Xenopus laevis

PubMed Central

Perry, Kimberly J.; Johnson, Verity R.; Malloch, Erica L.; Fukui, Lisa; Wever, Jason; Thomas, Alvin G.; Hamilton, Paul W.; Henry, Jonathan J.

2010-01-01

G-protein-coupled receptors (GPCRs) represent diverse, multifamily groups of cell signaling receptors involved in many cellular processes. We identified Xenopus laevis GPR84 as a member of the A18 subfamily of GPCRs. During development, GPR84 is detected in the embryonic lens placode, differentiating lens fiber cells, retina and cornea. Anti-sense morpholino oligonucleotide-mediated knockdown and RNA rescue experiments demonstrate GPR84’s importance in lens, cornea and retinal development. Examination of cell proliferation using an antibody against histone H3 S10P reveals significant increases in the lens and retina following GPR84 knockdown. Additionally, there was also an increase in apoptosis in the retina and lens, as revealed by TUNEL assay. Reciprocal transplantation of the presumptive lens ectoderm between uninjected controls and morpholino injected embryos demonstrates that GPR84 is necessary in the retina for proper development of the retina, as well as other eye tissues including the lens and cornea. PMID:20925114

An RNA tool kit to study the status of mouse ES cells: sex determination and stemness.

PubMed

Jay, F; Ciaudo, C

2013-09-01

Mouse embryonic stem cells (mESCs) are pluripotent stem cells derived from the inner cell mass of the blastocyst. They can be maintained under controlled culture conditions in a pluripotent state, or be induced to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. Several studies have characterised the coding and non-coding (nc) RNA repertoires of mESCs, uncovering highly dynamic variations during the process of differentiation, but also qualitative differences pertaining to sex. For example, up-regulation of the long non-coding RNA Xist on the X chromosome induces gene silencing and X inactivation exclusively during female mESC differentiation. In contrast, specific small RNAs have been shown to be up-regulated during male mESC differentiation. Here, we illustrate how a small set of key coding and ncRNAs can be exploited as dynamic and sensitive markers of the stemness and/or the differentiation status of male or female mESC lines. We describe adapted techniques for the extended characterization and analysis of mESCs from as little material as that cultured in a single 75cm(2) flask. Copyright © 2013 Elsevier Inc. All rights reserved.

Gene therapy of murine teratocarcinoma: separate functions for insulin-like growth factors I and II in immunogenicity and differentiation.

PubMed Central

Trojan, J; Johnson, T R; Rudin, S D; Blossey, B K; Kelley, K M; Shevelev, A; Abdul-Karim, F W; Anthony, D D; Tykocinski, M L; Ilan, J

1994-01-01

Teratocarcinoma is a germ-line carcinoma giving rise to an embryoid tumor with structures derived from the three embryonic layers: mesoderm, endoderm, and ectoderm. Teratocarcinoma is widely used as an in vitro model system to study regulation of cell determination and differentiation during mammalian embryogenesis. Murine embryonic carcinoma (EC) PCC3 cells express insulin-like growth factor I(IGF-I) and its receptor, while all derivative tumor structures express IGF-I and IGF-II and their receptors. Therefore the system lends itself to dissect the role of these two growth factors during EC differentiation. With an episomal antisense strategy, we define a role for IGF-I in tumorigenicity and evasion of immune surveillance. Antisense IGF-I EC transfectants are shown to elicit a curative anti-tumor immune response with tumor regression at distal sites. In contrast, IGF-II is shown to drive determination and differentiation in EC cells. Since IGF-I and IGF-II bind to type I receptor and antisense sequence used for IGF-II cannot form duplex with endogenous IGF-I transcripts, it follows that this receptor is not involved in determination and differentiation. Images PMID:8016120

Human mesenchymal stem cells - current trends and future prospective

PubMed Central

Ullah, Imran; Subbarao, Raghavendra Baregundi; Rho, Gyu Jin

2015-01-01

Stem cells are cells specialized cell, capable of renewing themselves through cell division and can differentiate into multi-lineage cells. These cells are categorized as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells. Mesenchymal stem cells (MSCs) are adult stem cells which can be isolated from human and animal sources. Human MSCs (hMSCs) are the non-haematopoietic, multipotent stem cells with the capacity to differentiate into mesodermal lineage such as osteocytes, adipocytes and chondrocytes as well ectodermal (neurocytes) and endodermal lineages (hepatocytes). MSCs express cell surface markers like cluster of differentiation (CD)29, CD44, CD73, CD90, CD105 and lack the expression of CD14, CD34, CD45 and HLA (human leucocyte antigen)-DR. hMSCs for the first time were reported in the bone marrow and till now they have been isolated from various tissues, including adipose tissue, amniotic fluid, endometrium, dental tissues, umbilical cord and Wharton's jelly which harbours potential MSCs. hMSCs have been cultured long-term in specific media without any severe abnormalities. Furthermore, MSCs have immunomodulatory features, secrete cytokines and immune-receptors which regulate the microenvironment in the host tissue. Multilineage potential, immunomodulation and secretion of anti-inflammatory molecules makes MSCs an effective tool in the treatment of chronic diseases. In the present review, we have highlighted recent research findings in the area of hMSCs sources, expression of cell surface markers, long-term in vitro culturing, in vitro differentiation potential, immunomodulatory features, its homing capacity, banking and cryopreservation, its application in the treatment of chronic diseases and its use in clinical trials. PMID:25797907

The future of research in craniofacial biology and what this will mean for oral health professional education and clinical practice.

PubMed

Slavkin, H C

2014-06-01

Today, and looking to the future, scientific discoveries from cellular, developmental and molecular biology inform our understanding of cell, tissue and organ morphogenesis as exemplified in skin, bone, cartilage, dentine, enamel, muscle, nerve and many organs such as salivary glands and teeth. Present day biomedical science yields principles for the biomimetic design and fabrication of cells, tissues and organs. Bioengineering has become a strategy that can 'mimic' biological processes, and inform clinical procedures for tissue and organ replacements. The future of regenerative craniofacial biology holds enormous promise for the diagnosis and treatment of congenital birth defects, traumatic injuries, degenerative chronic diseases as well as for Mendelian single gene and complex multigene diseases and disorders. The past 50 years have heralded the completion of the human genome and the introduction of 'personalized medicine and dentistry', the utilization of stem cell therapy for an array of diseases and disorders, the 'proof of principle' to reverse select inherited diseases such as anhidrotic ectodermal dysplasia (ED), and the fruits from interdisciplinary research drawn from the diverse biomedical sciences. Looking to the future, we can readily anticipate as major goals to emphasize the clinician's role in identifying clinical phenotypes that can lead to differential diagnosis, and rejuvenate missing or damaged tissues by establishing processes for the utilization of gene, cell and/or protein therapies. The future is replete with remarkable opportunities to enhance clinical outcomes for congenital as well as acquired craniofacial malformations. Clinicians play a pivotal role because critical thinking and sound clinical acumen substantially improve diagnostic precision and thereby clinical health outcomes. © 2014 Australian Dental Association.

Role of adipose tissue-derived stem cells in the progression of renal disease.

PubMed

Donizetti-Oliveira, Cassiano; Semedo, Patricia; Burgos-Silva, Marina; Cenedeze, Marco Antonio; Malheiros, Denise Maria Avancini Costa; Reis, Marlene Antônia Dos; Pacheco-Silva, Alvaro; Câmara, Niels Olsen Saraiva

2011-03-01

To analyze the role of adipose tissue-derived stem cells in reducing the progression of renal fibrosis. adipose tissue-derived stem cells were isolated from C57Bl/6 mice and characterized by cytometry and differentiation. Renal fibrosis was established after unilateral clamping of the renal pedicle for 1 hour. Four hours after reperfusion, 2.105 adipose tissue-derived stem cells were administered intraperitoneally and the animals were followed for 24 hours during 6 weeks. In another experimental group, 2.105adipose tissue-derived stem cells were administered only after 6 weeks of reperfusion, and they were euthanized and studied 4 weeks later. Twenty-four hours after reperfusion, the animals treated with adipose tissue-derived stem cells displayed reduced renal and tubular dysfunction and an increase of the regenerative process. Renal expression of IL-6 and TNF mRNA were decreased in the animals treated with adipose tissue-derived stem cells, while the levels of IL-4, IL-10, and HO-1 were increased, despite the fact that adipose tissue-derived stem cells were not observed in the kidneys via SRY analysis. In 6 weeks, the kidneys of non-treated animals decreased in size, and the kidneys of the animals treated with adipose tissue-derived stem cells remained at normal size and display less deposition of type 1 collagen and FSP-1. The renal protection observed in animals treated with adipose tissue-derived stem cells was followed by a drop in serum levels of TNF-α, KC, RANTES, and IL-1a. Treatment with adipose tissue-derived stem cells after 6 weeks, when the animals already displayed established fibrosis, demonstrated an improvement in functional parameters and less fibrosis analyzed by Picrosirius stain, as well as a reduction of the expression of type 1 collagen and vimentin mRNA. Treatment with adipose tissue-derived stem cells may deter the progression of renal fibrosis by modulation of the early inflammatory response, likely via reduction of the epithelial-mesenchymal transition.

Genetics Home Reference: focal dermal hypoplasia

MedlinePlus

... in people with focal dermal hypoplasia is an omphalocele , which is an opening in the wall of ... Dermal Hypoplasia MedlinePlus Encyclopedia: Ectodermal dysplasia MedlinePlus Encyclopedia: Omphalocele General Information from MedlinePlus (5 links) Diagnostic Tests ...

Induced Pluripotent Stem (iPS) Cells in Dentistry: A Review

PubMed Central

Malhotra, Neeraj

2016-01-01

iPS cells are derived from somatic cells via transduction and expression of selective transcription factors. Both viral-integrating (like retroviral) and non-integrating (like, mRNA or protein-based) techniques are available for the production of iPS cells. In the field of dentistry, iPS cells have been derived from stem cells of apical papilla, dental pulp stem cells, and stem cells from exfoliated deciduous teeth, gingival and periodontal ligament fibroblasts, and buccal mucosa fibroblasts. iPS cells have the potential to differentiate into all derivatives of the 3 primary germ layers i.e. ectoderm, endoderm, and mesoderm. They are autogeneically accessible, and can produce patient-specific or disease-specific cell lines without the issue of ethical controversy. They have been successfully tested to produce mesenchymal stem cells-like cells, neural crest-like cells, ameloblasts-like cells, odontoblasts-like cells, and osteoprogenitor cells. These cells can aid in regeneration of periodontal ligament, alveolar bone, cementum, dentin-pulp complex, as well as possible Biotooth formation. However certain key issues like, epigenetic memory of iPS cells, viral-transduction, tumorgenesis and teratoma formation need to be overcome, before they can be successfully used in clinical practice. The article discusses the sources, pros and cons, and current applications of iPS cells in dentistry with an emphasis on encountered challenges and their solutions. PMID:27572712

Autoimmune Regulator (AIRE) Is Expressed in Spermatogenic Cells, and It Altered the Expression of Several Nucleic-Acid-Binding and Cytoskeletal Proteins in Germ Cell 1 Spermatogonial (GC1-spg) Cells.

PubMed

Radhakrishnan, Karthika; Bhagya, Kongattu P; Kumar, Anil Tr; Devi, Anandavalli N; Sengottaiyan, Jeeva; Kumar, Pradeep G

2016-08-01

Autoimmune regulator (AIRE) is a gene associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). AIRE is expressed heavily in the thymic epithelial cells and is involved in maintaining self-tolerance through regulating the expression of tissue-specific antigens. The testes are the most predominant extrathymic location where a heavy expression of AIRE is reported. Homozygous Aire-deficient male mice were infertile, possibly due to impaired spermatogenesis, deregulated germ cell apoptosis, or autoimmunity. We report that AIRE is expressed in the testes of neonatal, adolescent, and adult mice. AIRE expression was detected in glial cell derived neurotrophic factor receptor alpha (GFRα)(+) (spermatogonia), GFRα(-)/synaptonemal complex protein (SCP3)(+) (meiotic), and GFRα(-)/Phosphoglycerate kinase 2 (PGK2)(+) (postmeiotic) germ cells in mouse testes. GC1-spg, a germ-cell-derived cell line, did not express AIRE. Retinoic acid induced AIRE expression in GC1-spg cells. Ectopic expression of AIRE in GC1-spg cells using label-free LC-MS/MS identified a total of 371 proteins that were differentially expressed. 100 proteins were up-regulated, and 271 proteins were down-regulated. Data are available via ProteomeXchange with identifier PXD002511. Functional analysis of the differentially expressed proteins showed increased levels of various nucleic-acid-binding proteins and transcription factors and a decreased level of various cytoskeletal and structural proteins in the AIRE overexpressing cells as compared with the empty vector-transfected controls. The transcripts of a select set of the up-regulated proteins were also elevated. However, there was no corresponding decrease in the mRNA levels of the down-regulated set of proteins. Molecular function network analysis indicated that AIRE influenced gene expression in GC1-spg cells by acting at multiple levels, including transcription, translation, RNA processing, protein transport, protein localization, and protein degradation, thus setting the foundation in understanding the functional role of AIRE in germ cell biology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification of a Novel Proto-oncogenic Network in Head and Neck Squamous Cell Carcinoma.

PubMed

Georgy, Smitha R; Cangkrama, Michael; Srivastava, Seema; Partridge, Darren; Auden, Alana; Dworkin, Sebastian; McLean, Catriona A; Jane, Stephen M; Darido, Charbel

2015-09-01

The developmental transcription factor Grainyhead-like 3 (GRHL3) plays a critical tumor suppressor role in the mammalian epidermis through direct regulation of PTEN and the PI3K/AKT/mTOR signaling pathway. GRHL3 is highly expressed in all tissues derived from the surface ectoderm, including the oral cavity, raising a question about its potential role in suppression of head and neck squamous cell carcinoma (HNSCC). We explored the tumor suppressor role of Grhl3 in HNSCC using a conditional knockout (Grhl3 (∆/-) /K14Cre (+) ) mouse line (n = 26) exposed to an oral chemical carcinogen. We defined the proto-oncogenic pathway activated in the HNSCC derived from these mice and assessed it in primary human HNSCC samples, normal oral epithelial cell lines carrying shRNA to GRHL3, and human HNSCC cell lines. Data were analyzed with two-sided chi square and Student's t tests. Deletion of Grhl3 in oral epithelium in mice did not perturb PTEN/PI3K/AKT/mTOR signaling, but instead evoked loss of GSK3B expression, resulting in stabilization and accumulation of c-MYC and aggressive HNSCC. This molecular signature was also evident in a subset of primary human HNSCC and HNSCC cell lines. Loss of Gsk3b in mice, independent of Grhl3, predisposed to chemical-induced HNSCC. Restoration of GSK3B expression blocked proliferation of normal oral epithelial cell lines carrying shRNA to GRHL3 (cell no., Day 8: Scramble ctl, 616±21.8 x 10(3) vs GRHL3-kd, 1194±44 X 10(3), P < .001; GRHL3-kd vs GRHL3-kd + GSK3B, 800±98.84 X 10(3), P = .003) and human HNSCC cells. We defined a novel molecular signature in mammalian HNSCC, suggesting new treatment strategies targeting the GRHL3/GSK3B/c-MYC proto-oncogenic network. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Application of a novel sorting system for equine mesenchymal stem cells (MSCs)

PubMed Central

Radtke, Catherine L.; Nino-Fong, Rodolfo; Esparza Gonzalez, Blanca P.; McDuffee, Laurie A.

2014-01-01

The objective of this study was to validate non-equilibrium gravitational field-flow fractionation (GrFFF), an immunotag-less method of sorting mesenchymal stem cells (MSCs) into subpopulations, for use with MSCs derived from equine muscle tissue, periosteal tissue, bone marrow, and adipose tissue. Cells were collected from 6 young, adult horses, postmortem. Cells were isolated from left semitendinosus muscle tissue, periosteal tissue from the distomedial aspect of the right tibia, bone marrow aspirates from the fourth and fifth sternebrae, and left supragluteal subcutaneous adipose tissue. Aliquots of 800 × 103 MSCs from each tissue source were separated and injected into a ribbon-like capillary device by continuous flow (GrFFF proprietary system). Cells were sorted into 6 fractions and absorbencies [optical density (OD)] were read. Six fractions from each of the 6 aliquots were then combined to provide pooled fractions that had adequate cell numbers to seed at equal concentrations into assays. Equine muscle tissue-derived, periosteal tissue-derived, bone marrow-derived, and adipose tissue-derived mesenchymal stem cells were consistently sorted into 6 fractions that remained viable for use in further assays. Fraction 1 had more cuboidal morphology in culture when compared to the other fractions. Statistical analysis of the fraction absorbencies (OD) revealed a P-value of < 0.05 when fractions 2 and 3 were compared to fractions 1, 4, 5, and 6. It was concluded that non-equilibrium GrFFF is a valid method for sorting equine muscle tissue-derived, periosteal tissue-derived, bone marrow-derived, and adipose tissue-derived mesenchymal stem cells into subpopulations that remain viable, thus securing its potential for use in equine stem cell applications and veterinary medicine. PMID:25355998

Amino-terminal residues of ΔNp63, mutated in ectodermal dysplasia, are required for its transcriptional activity.

PubMed

Lena, Anna Maria; Duca, Sara; Novelli, Flavia; Melino, Sonia; Annicchiarico-Petruzzelli, Margherita; Melino, Gerry; Candi, Eleonora

2015-11-13

p63, a member of the p53 family, is a crucial transcription factor for epithelial development and skin homeostasis. Heterozygous mutations in TP63 gene have been associated with human ectodermal dysplasia disorders. Most of these TP63 mutations are missense mutations causing amino acidic substitutions at p63 DNA binding or SAM domains that reduce or abolish the transcriptional activity of mutants p63. A significant number of mutants, however, resides in part of the p63 protein that apparently do not affect DNA binding and/or transcriptional activity, such as the N-terminal domain. Here, we characterize five p63 mutations at the 5' end of TP63 gene aiming to understand the pathogenesis of the diseases and to uncover the role of ΔNp63α N-terminus residues in determining its transactivation potential. Copyright © 2015 Elsevier Inc. All rights reserved.

Drosophila heart cell movement to the midline occurs through both cell autonomous migration and dorsal closure.

PubMed

Haack, Timm; Schneider, Matthias; Schwendele, Bernd; Renault, Andrew D

2014-12-15

The Drosophila heart is a linear organ formed by the movement of bilaterally specified progenitor cells to the midline and adherence of contralateral heart cells. This movement occurs through the attachment of heart cells to the overlying ectoderm which is undergoing dorsal closure. Therefore heart cells are thought to move to the midline passively. Through live imaging experiments and analysis of mutants that affect the speed of dorsal closure we show that heart cells in Drosophila are autonomously migratory and part of their movement to the midline is independent of the ectoderm. This means that heart formation in flies is more similar to that in vertebrates than previously thought. We also show that defects in dorsal closure can result in failure of the amnioserosa to properly degenerate, which can physically hinder joining of contralateral heart cells leading to a broken heart phenotype. Copyright © 2014 Elsevier Inc. All rights reserved.

Platelet-rich plasma-an 'Elixir' for treatment of alopecia: personal experience on 117 patients with review of literature.

PubMed

Garg, Suruchi; Manchanda, Shweta

2017-01-01

Platelet-rich plasma (PRP) has emerged as a new treatment modality in regenerative plastic surgery and dermatology. PRP is a simple, cost-effective and feasible treatment option with high patient satisfaction for hair loss and can be regarded as a valuable adjuvant treatment modality for androgenic alopecia and other types of non-scarring alopecias. Authors have proposed a hair model termed "Golden anchorage with 'molecular locking' of ectodermal and mesenchymal components for survival and integrity of hair follicle (HF)" in this article. Golden anchorage comprises of bulge stem cells, ectodermal basement membrane and bulge portion of APM. PRP with its autologous supply of millions of growth factors works on 'Golden anchorage' along with keratinocytes (PDGF), dermal papilla (IGF and fibroblast growth factor), vasculature (VEGF and PDGF) and neural cells (Nerve Growth Factor) in a multipronged manner serving as an 'elixir' for hair growth and improving overall environment.

RNA-Seq identifies SPGs as a ventral skeletal patterning cue in sea urchins.

PubMed

Piacentino, Michael L; Zuch, Daniel T; Fishman, Julie; Rose, Sviatlana; Speranza, Emily E; Li, Christy; Yu, Jia; Chung, Oliver; Ramachandran, Janani; Ferrell, Patrick; Patel, Vijeta; Reyna, Arlene; Hameeduddin, Hajerah; Chaves, James; Hewitt, Finnegan B; Bardot, Evan; Lee, David; Core, Amanda B; Hogan, John D; Keenan, Jessica L; Luo, Lingqi; Coulombe-Huntington, Jasmin; Blute, Todd A; Oleinik, Ekaterina; Ibn-Salem, Jonas; Poustka, Albert J; Bradham, Cynthia A

2016-02-15

The sea urchin larval skeleton offers a simple model for formation of developmental patterns. The calcium carbonate skeleton is secreted by primary mesenchyme cells (PMCs) in response to largely unknown patterning cues expressed by the ectoderm. To discover novel ectodermal cues, we performed an unbiased RNA-Seq-based screen and functionally tested candidates; we thereby identified several novel skeletal patterning cues. Among these, we show that SLC26a2/7 is a ventrally expressed sulfate transporter that promotes a ventral accumulation of sulfated proteoglycans, which is required for ventral PMC positioning and skeletal patterning. We show that the effects of SLC perturbation are mimicked by manipulation of either external sulfate levels or proteoglycan sulfation. These results identify novel skeletal patterning genes and demonstrate that ventral proteoglycan sulfation serves as a positional cue for sea urchin skeletal patterning. © 2016. Published by The Company of Biologists Ltd.

[On the nervous system of a parasitic cnidarian Polypodium hydriforme].

PubMed

Raĭkova, E V

2013-01-01

Nerve cells in a parasitic cnidarian Polypodium hydriforme at the parasitic and free-living stages of the life cycle have been localized immunocytochemically using antibodies to FMRF-amide, and their ultrastructure has been described. Ganglion cells form a net under epidermis consisting of bi- and tripolar neurons which cross the mesoglea and usually contact muscle cells and cnidocytes. Fusiform sensory and neurosecretory cells, especially characteristic to sensory tentacles, are interspersed among epidermal cells. All three types of nerve cells have dense cored vesicles about 80-120 nm in diameter. The sensory cells demonstrate a sensory flagellum-like immobile structure. Neurosecretory and sensory cells form septate junctions with epidermal cells. Ganglion cells show gap junctions between them. A centriole encircled by a fragment of nuclear envelope which is a marker of ectodermal lineage cells in Polypodium has been described in the cytoplasm of a sensory cell, thus proving the ectodermal nature of the nervous system.

Telescopic overdenture for oral rehabilitation of ectodermal dysplasia patient.

PubMed

Gupta, Charu; Verma, Mahesh; Gupta, Rekha; Gill, Shubhra

2015-09-01

Reduced number of teeth with underdeveloped alveolar ridges poses a greatest prosthetic challenge in rehabilitation of ectodermal dysplasia patients (ED). Furthermore, surgical risks and financial constraints may preclude the implant supported prosthesis, the most desirable treatment option in an adult ED patient. Long edentulous span does not permit fixed dental prosthesis (FDP) as well. Telescopic denture by incorporating the best of both fixed and removable prosthesis can be a viable treatment alternative for ED patients with compromised dentition and limited finances. A 21-year-old young girl presented with chief complaint of esthetics and mastication due to missing upper and lower teeth. A provisional diagnosis of ED was made based on familial history, physical, and oral examination. This clinical report describes management of an adult ED patient by means of telescopic overdenture prosthesis in mandibular arch and FDP in maxillary arch which restored esthetics, function, and social confidence of the patient in a cost effective manner.

Telescopic overdenture for oral rehabilitation of ectodermal dysplasia patient

PubMed Central

Gupta, Charu; Verma, Mahesh; Gupta, Rekha; Gill, Shubhra

2015-01-01

Reduced number of teeth with underdeveloped alveolar ridges poses a greatest prosthetic challenge in rehabilitation of ectodermal dysplasia patients (ED). Furthermore, surgical risks and financial constraints may preclude the implant supported prosthesis, the most desirable treatment option in an adult ED patient. Long edentulous span does not permit fixed dental prosthesis (FDP) as well. Telescopic denture by incorporating the best of both fixed and removable prosthesis can be a viable treatment alternative for ED patients with compromised dentition and limited finances. A 21-year-old young girl presented with chief complaint of esthetics and mastication due to missing upper and lower teeth. A provisional diagnosis of ED was made based on familial history, physical, and oral examination. This clinical report describes management of an adult ED patient by means of telescopic overdenture prosthesis in mandibular arch and FDP in maxillary arch which restored esthetics, function, and social confidence of the patient in a cost effective manner. PMID:26604583

Expression of the ctenophore Brain Factor 1 forkhead gene ortholog (ctenoBF-1) mRNA is restricted to the presumptive mouth and feeding apparatus: implications for axial organization in the Metazoa

NASA Technical Reports Server (NTRS)

Yamada, Atsuko; Martindale, Mark Q.

2002-01-01

Ctenophores are thoroughly modern animals whose ancestors are derived from a separate evolutionary branch than that of other eumetazoans. Their major longitudinal body axis is the oral-aboral axis. An apical sense organ, called the apical organ, is located at the aboral pole and contains a highly innervated statocyst and photodetecting cells. The apical organ integrates sensory information and controls the locomotory apparatus of ctenophores, the eight longitudinal rows of ctene/comb plates. In an effort to understand the developmental and evolutionary organization of axial properties of ctenophores we have isolated a forkhead gene from the Brain Factor 1 (BF-1) family. This gene, ctenoBF-1, is the first full-length nuclear gene reported from ctenophores. This makes ctenophores the most basal metazoan (to date) known to express definitive forkhead class transcription factors. Orthologs of BF-1 in vertebrates, Drosophila, and Caenorhabditis elegans are expressed in anterior neural structures. Surprisingly, in situ hybridizations with ctenoBF-1 antisense riboprobes show that this gene is not expressed in the apical organ of ctenophores. CtenoBF-1 is expressed prior to first cleavage. Transcripts become localized to the aboral pole by the 8-cell stage and are inherited by ectodermal micromeres generated from this region at the 16- and 32-cell stages. Expression in subsets of these cells persists and is seen around the edge of the blastopore (presumptive mouth) and in distinct ectodermal regions along the tentacular poles. Following gastrulation, stomodeal expression begins to fade and intense staining becomes restricted to two distinct domains in each tentacular feeding apparatus. We suggest that the apical organ is not homologous to the brain of bilaterians but that the oral pole of ctenophores corresponds to the anterior pole of bilaterian animals.

X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry.

PubMed

Fete, Mary; Hermann, Julie; Behrens, Jeffrey; Huttner, Kenneth M

2014-10-01

The web-based Ectodermal Dysplasia International Registry (EDIR) is a comprehensive patient-reported survey contributing to an understanding of ectodermal dysplasia (ED). XLHED is the most common of the genetic ED syndromes and was the primary diagnosis reported by 223/835 respondents (141 males and 82 females). Overall, 96% of XLHED registrants reported as least one other affected family member and 21% reported a family history of infant or childhood deaths, consistent with the published mortality data in this disorder. In general, XLHED is diagnosed by the triad of decreased sweating, reduced hair, and hypodontia (present in 89%, 74%, and 74% of XLHED respondents). Additionally, the registry dataset confirmed a spectrum of life-long XLHED clinical complications including recurrent sinus infections (49% males, 52% females), nasal congestion often foul smelling and interfering with feeding (73% males, 27% females), eczema (66% males, 40% females), wheezing (66% males, 45% females), and a hoarse, raspy voice (67% males, 23% females). The Registry results also highlighted features consistently differentiating XLHED from the non-hypohidrotic ED syndromes including the frequency of infant/childhood deaths, the presence of limb/digit abnormalities, feeding issues related to nasal discharge, dentures, and a diagnosis of asthma. These results represent the largest collection of data on a broad-spectrum of health-related issues affecting ED patients. This project provides information for expanding knowledge of the natural history of XLHED, and as such may facilitate the diagnosis and treatment of its varied and lifelong medical challenges. © 2014 Wiley Periodicals, Inc.

Disturbances of dental development distinguish patients with oligodontia-ectodermal dysplasia from isolated oligodontia.

PubMed

Dhamo, B; Kuijpers, M A R; Balk-Leurs, I; Boxum, C; Wolvius, E B; Ongkosuwito, E M

2018-02-01

To investigate phenotypic differences in dental development between isolated oligodontia and oligodontia-ectodermal dysplasia (ED). A total of 129 patients diagnosed with isolated oligodontia and 22 patients with oligodontia as part of ED were eligible. The phenotype of dental development was assessed for the frequency of missing a certain tooth, dental age, development of each tooth present, abnormal size and abnormal shape of teeth. The data were analysed building linear, ordinal and logistic regression models. Compared to patients with isolated oligodontia, patients with oligodontia-ED missed more frequently central incisors and second molars in both jaws, and lateral incisors in the mandible (P < .05). Oligodontia-ED was associated with delayed development of the permanent dentition (β = -0.10; 95% CI: -0.17, -0.03). Specifically, the maxillary teeth: right central incisor, right lateral incisor, right second premolar and left second premolar were delayed approximately from 2 to 4 developmental stages. In addition, the left mandibular second premolar was 3 developmental stages delayed. Abnormal shape of teeth was 7 times more evident in patients with oligodontia-ED compared to patients with isolated oligodontia (OR = 6.54; 95% CI: 2.34, 18.28). The abnormal size of teeth was not a distinctive characteristic for oligodontia-ED. Oligodontia-ED distinguishes from isolated oligodontia by more disturbances in dental development. The abnormal shape of incisors and canines in a patient with oligodontia can raise suspicions for accompanying ectodermal abnormalities. © 2017 The Authors. Orthodontics & Craniofacial Research Published by John Wiley & Sons Ltd.

Using a Paradigm Shift to Teach Neurobiology and the Nature of Science-a C.R.E.A.T.E.-based Approach.

PubMed

Hoskins, Sally G

2008-01-01

Decades ago, classic experiments established the phenomenon of "neural induction" (Spemann and Mangold, 1924; Holtfreter, 1933). It appeared clear that amphibian ectoderm was pre-programmed to form epidermis, and that the neural phenotype was induced by a chemical signal from mesoderm. The "ectoderm makes skin, unless induced to make nervous system" model appeared in many textbooks. This interpretation, however, was not simply incorrect but 180 degrees out of alignment with the actual situation. As subsequently demonstrated, the default state of amphibian ectoderm is neuronal, and the expression of the epidermal phenotype requires cell signaling (Hemmati-Brivanlou and Melton, 1992; 1994; 1997). In this activity, students are presented with key experiments in a stepwise fashion. At several points, they work in groups to devise models that explain particular experimental results. The stepwise presentation of results mirrors the history of discoveries in this experimental system. Eventually, faced with seemingly contradictory data, students must revise their models substantially and in doing so, experience the paradigm shift. The lesson also examines the history of this paradigm shift. Data inconsistent with the "epidermal default" model were published years before the "neural default" model was proposed, but the significance of the surprising new data was underemphasized by the scientists who made the discovery. Discussing this situation provides insight into how science works and highlights the possibility that working scientists may become entrenched in prevailing paradigms. Such "nature of science" discussions emphasize research as a human activity, and help to dispel student misconceptions about science and scientists.

Variable phenotypic penetrance of thrombosis in adult mice after tissue-selective and temporally controlled Thbd gene inactivation

PubMed Central

van Mens, Thijs E.; Liang, Hai-Po H.; Basu, Sreemanti; Hernandez, Irene; Zogg, Mark; May, Jennifer; Zhan, Min; Yang, Qiuhui; Foeckler, Jamie; Kalloway, Shawn; Sood, Rashmi; Karlson, Caren Sue

2017-01-01

Thrombomodulin (Thbd) exerts pleiotropic effects on blood coagulation, fibrinolysis, and complement system activity by facilitating the thrombin-mediated activation of protein C and thrombin-activatable fibrinolysis inhibitor and may have additional thrombin- and protein C (pC)-independent functions. In mice, complete Thbd deficiency causes embryonic death due to defective placental development. In this study, we used tissue-selective and temporally controlled Thbd gene ablation to examine the function of Thbd in adult mice. Selective preservation of Thbd function in the extraembryonic ectoderm and primitive endoderm via the Meox2Cre-transgene enabled normal intrauterine development of Thbd-deficient (Thbd−/−) mice to term. Half of the Thbd−/− offspring expired perinatally due to thrombohemorrhagic lesions. Surviving Thbd−/− animals only rarely developed overt thrombotic lesions, exhibited low-grade compensated consumptive coagulopathy, and yet exhibited marked, sudden-onset mortality. A corresponding pathology was seen in mice in which the Thbd gene was ablated after reaching adulthood. Supplementation of activated PC by transgenic expression of a partially Thbd-independent murine pC zymogen prevented the pathologies of Thbd−/− mice. However, Thbd−/− females expressing the PC transgene exhibited pregnancy-induced morbidity and mortality with near-complete penetrance. These findings suggest that Thbd function in nonendothelial embryonic tissues of the placenta and yolk sac affects through as-yet-unknown mechanisms the penetrance and severity of thrombosis after birth and provide novel opportunities to study the role of the natural Thbd-pC pathway in adult mice and during pregnancy. PMID:28920104

Dynamics of Mouth Opening in Hydra

PubMed Central

Carter, Jason A.; Hyland, Callen; Steele, Robert E.; Collins, Eva-Maria S.

2016-01-01

Hydra, a simple freshwater animal famous for its regenerative capabilities, must tear a hole through its epithelial tissue each time it opens its mouth. The feeding response of Hydra has been well-characterized physiologically and is regarded as a classical model system for environmental chemical biology. However, due to a lack of in vivo labeling and imaging tools, the biomechanics of mouth opening have remained completely unexplored. We take advantage of the availability of transgenic Hydra lines to perform the first dynamical analysis, to our knowledge, of Hydra mouth opening and test existing hypotheses regarding the underlying cellular mechanisms. Through cell position and shape tracking, we show that mouth opening is accompanied by changes in cell shape, but not cellular rearrangements as previously suggested. Treatment with a muscle relaxant impairs mouth opening, supporting the hypothesis that mouth opening is an active process driven by radial contractile processes (myonemes) in the ectoderm. Furthermore, we find that all events exhibit the same relative rate of opening. Because one individual can open consecutively to different amounts, this suggests that the degree of mouth opening is controlled through neuronal signaling. Finally, from the opening dynamics and independent measurements of the elastic properties of the tissues, we estimate the forces exerted by the myonemes to be on the order of a few nanoNewtons. Our study provides the first dynamical framework, to our knowledge, for understanding the remarkable plasticity of the Hydra mouth and illustrates that Hydra is a powerful system for quantitative biomechanical studies of cell and tissue behaviors in vivo. PMID:26958895

Dynamics of Mouth Opening in Hydra.

PubMed

Carter, Jason A; Hyland, Callen; Steele, Robert E; Collins, Eva-Maria S

2016-03-08

Hydra, a simple freshwater animal famous for its regenerative capabilities, must tear a hole through its epithelial tissue each time it opens its mouth. The feeding response of Hydra has been well-characterized physiologically and is regarded as a classical model system for environmental chemical biology. However, due to a lack of in vivo labeling and imaging tools, the biomechanics of mouth opening have remained completely unexplored. We take advantage of the availability of transgenic Hydra lines to perform the first dynamical analysis, to our knowledge, of Hydra mouth opening and test existing hypotheses regarding the underlying cellular mechanisms. Through cell position and shape tracking, we show that mouth opening is accompanied by changes in cell shape, but not cellular rearrangements as previously suggested. Treatment with a muscle relaxant impairs mouth opening, supporting the hypothesis that mouth opening is an active process driven by radial contractile processes (myonemes) in the ectoderm. Furthermore, we find that all events exhibit the same relative rate of opening. Because one individual can open consecutively to different amounts, this suggests that the degree of mouth opening is controlled through neuronal signaling. Finally, from the opening dynamics and independent measurements of the elastic properties of the tissues, we estimate the forces exerted by the myonemes to be on the order of a few nanoNewtons. Our study provides the first dynamical framework, to our knowledge, for understanding the remarkable plasticity of the Hydra mouth and illustrates that Hydra is a powerful system for quantitative biomechanical studies of cell and tissue behaviors in vivo. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Genetics Home Reference: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

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... production of the hormone insulin; a shortage of growth hormone leading to short stature; problems affecting the internal ... promotes the production of certain antimicrobial protein segments (peptides) that control growth of Candida on the surface of mucous membranes. ...