Relation between obesity and bone mineral density and vertebral fractures in Korean postmenopausal women.

PubMed

Kim, Kyong-Chol; Shin, Dong-Hyuk; Lee, Sei-Young; Im, Jee-Aee; Lee, Duk-Chul

2010-11-01

The traditional belief that obesity is protective against osteoporosis has been questioned. Recent epidemiologic studies show that body fat itself may be a risk factor for osteoporosis and bone fractures. Accumulating evidence suggests that metabolic syndrome and the individual components of metabolic syndrome such as hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol are also risk factors for low bone mineral density. Using a cross sectional study design, we evaluated the associations between obesity or metabolic syndrome and bone mineral density (BMD) or vertebral fracture. A total of 907 postmenopausal healthy female subjects, aged 60-79 years, were recruited from woman hospitals in Seoul, South Korea. BMD, vetebral fracture, bone markers, and body composition including body weight, body mass index (BMI), percentage body fat, and waist circumference were measured. After adjusting for age, smoking status, alcohol consumption, total calcium intake, and total energy intake, waist circumference was negatively related to BMD of all sites (lumbar BMD p = 0.037, all sites of femur BMD p < 0.001) whereas body weight was still positively related to BMD of all sites (p < 0.001). Percentage body fat and waist circumference were much higher in the fracture group than the non-fracture group (p = 0.0383, 0.082 respectively). Serum glucose levels were positively correlated to lumbar BMD (p = 0.016), femoral neck BMD (p = 0.0335), and femoral trochanter BMD (p = 0.0082). Serum high density lipoprotein cholesterol (HDLC) was positively related to femoral trochanter BMD (p = 0.0366) and was lower in the control group than the fracture group (p = 0.011). In contrast to the effect favorable body weight on bone mineral density, high percentage body fat and waist circumference are related to low BMD and a vertebral fracture. Some components of metabolic syndrome were related to BMD and a vertebral fracture.

Notochord vacuoles are lysosome-related organelles that function in axis and spine morphogenesis.

PubMed

Ellis, Kathryn; Bagwell, Jennifer; Bagnat, Michel

2013-03-04

The notochord plays critical structural and signaling roles during vertebrate development. At the center of the vertebrate notochord is a large fluid-filled organelle, the notochord vacuole. Although these highly conserved intracellular structures have been described for decades, little is known about the molecular mechanisms involved in their biogenesis and maintenance. Here we show that zebrafish notochord vacuoles are specialized lysosome-related organelles whose formation and maintenance requires late endosomal trafficking regulated by the vacuole-specific Rab32a and H(+)-ATPase-dependent acidification. We establish that notochord vacuoles are required for body axis elongation during embryonic development and identify a novel role in spine morphogenesis. Thus, the vertebrate notochord plays important structural roles beyond early development.

Notochord vacuoles are lysosome-related organelles that function in axis and spine morphogenesis

PubMed Central

Ellis, Kathryn; Bagwell, Jennifer

2013-01-01

The notochord plays critical structural and signaling roles during vertebrate development. At the center of the vertebrate notochord is a large fluid-filled organelle, the notochord vacuole. Although these highly conserved intracellular structures have been described for decades, little is known about the molecular mechanisms involved in their biogenesis and maintenance. Here we show that zebrafish notochord vacuoles are specialized lysosome-related organelles whose formation and maintenance requires late endosomal trafficking regulated by the vacuole-specific Rab32a and H+-ATPase–dependent acidification. We establish that notochord vacuoles are required for body axis elongation during embryonic development and identify a novel role in spine morphogenesis. Thus, the vertebrate notochord plays important structural roles beyond early development. PMID:23460678

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis

PubMed Central

Ivanovitch, Kenzo; Temiño, Susana

2017-01-01

During vertebrate heart development, two progenitor populations, first and second heart fields (FHF, SHF), sequentially contribute to longitudinal subdivisions of the heart tube (HT), with the FHF contributing the left ventricle and part of the atria, and the SHF the rest of the heart. Here, we study the dynamics of cardiac differentiation and morphogenesis by tracking individual cells in live analysis of mouse embryos. We report that during an initial phase, FHF precursors differentiate rapidly to form a cardiac crescent, while limited morphogenesis takes place. In a second phase, no differentiation occurs while extensive morphogenesis, including splanchnic mesoderm sliding over the endoderm, results in HT formation. In a third phase, cardiac precursor differentiation resumes and contributes to SHF-derived regions and the dorsal closure of the HT. These results reveal tissue-level coordination between morphogenesis and differentiation during HT formation and provide a new framework to understand heart development. PMID:29202929

Morphogenesis underlying the development of the everted teleost telencephalon.

PubMed

Folgueira, Mónica; Bayley, Philippa; Navratilova, Pavla; Becker, Thomas S; Wilson, Stephen W; Clarke, Jonathan D W

2012-09-18

Although the mechanisms underlying brain patterning and regionalization are very much conserved, the morphology of different brain regions is extraordinarily variable across vertebrate phylogeny. This is especially manifest in the telencephalon, where the most dramatic variation is seen between ray-finned fish, which have an everted telencephalon, and all other vertebrates, which have an evaginated telencephalon. The mechanisms that generate these distinct morphologies are not well understood. Here we study the morphogenesis of the zebrafish telencephalon from 12 hours post fertilization (hpf) to 5 days post fertilization (dpf) by analyzing forebrain ventricle formation, evolving patterns of gene and transgene expression, neuronal organization, and fate mapping. Our results highlight two key events in telencephalon morphogenesis. First, the formation of a deep ventricular recess between telencephalon and diencephalon, the anterior intraencephalic sulcus (AIS), effectively creates a posterior ventricular wall to the telencephalic lobes. This process displaces the most posterior neuroepithelial territory of the telencephalon laterally. Second, as telencephalic growth and neurogenesis proceed between days 2 and 5 of development, the pallial region of the posterior ventricular wall of the telencephalon bulges into the dorsal aspect of the AIS. This brings the ventricular zone (VZ) into close apposition with the roof of the AIS to generate a narrow ventricular space and the thin tela choroidea (tc). As the pallial VZ expands, the tc also expands over the upper surface of the telencephalon. During this period, the major axis of growth and extension of the pallial VZ is along the anteroposterior axis. This second step effectively generates an everted telencephalon by 5 dpf. Our description of telencephalic morphogenesis challenges the conventional model that eversion is simply due to a laterally directed outfolding of the telencephalic neuroepithelium. This may have

Morphogenesis underlying the development of the everted teleost telencephalon

PubMed Central

2012-01-01

Background Although the mechanisms underlying brain patterning and regionalization are very much conserved, the morphology of different brain regions is extraordinarily variable across vertebrate phylogeny. This is especially manifest in the telencephalon, where the most dramatic variation is seen between ray-finned fish, which have an everted telencephalon, and all other vertebrates, which have an evaginated telencephalon. The mechanisms that generate these distinct morphologies are not well understood. Results Here we study the morphogenesis of the zebrafish telencephalon from 12 hours post fertilization (hpf) to 5 days post fertilization (dpf) by analyzing forebrain ventricle formation, evolving patterns of gene and transgene expression, neuronal organization, and fate mapping. Our results highlight two key events in telencephalon morphogenesis. First, the formation of a deep ventricular recess between telencephalon and diencephalon, the anterior intraencephalic sulcus (AIS), effectively creates a posterior ventricular wall to the telencephalic lobes. This process displaces the most posterior neuroepithelial territory of the telencephalon laterally. Second, as telencephalic growth and neurogenesis proceed between days 2 and 5 of development, the pallial region of the posterior ventricular wall of the telencephalon bulges into the dorsal aspect of the AIS. This brings the ventricular zone (VZ) into close apposition with the roof of the AIS to generate a narrow ventricular space and the thin tela choroidea (tc). As the pallial VZ expands, the tc also expands over the upper surface of the telencephalon. During this period, the major axis of growth and extension of the pallial VZ is along the anteroposterior axis. This second step effectively generates an everted telencephalon by 5 dpf. Conclusion Our description of telencephalic morphogenesis challenges the conventional model that eversion is simply due to a laterally directed outfolding of the telencephalic

Developmental expression of Hsp90, Hsp70 and HSF during morphogenesis in the vetigastropod Haliotis asinina.

PubMed

Gunter, Helen M; Degnan, Bernard M

2007-08-01

Heat shock proteins (Hsps) have dual functions, participating in both the stress response and a broad range of developmental processes. At physiological temperatures, it has been demonstrated in deuterostomes (vertebrates) and ecdysozoans (insects) that Hsps are expressed in tissues that are undergoing differentiation and morphogenesis. Here we investigate the developmental expression of Hsp70, Hsp90 and their regulatory transcription factor heat shock transcription factor (HSF) in the marine gastropod Haliotis asinina, a representative of the 3rd major lineage of bilaterian animals, the Lophotrochozoa. HasHsp70, HasHsp90 and HasHSF are maternally expressed in H. asinina and are progressively restricted to the micromere lineage during cleavage. During larval morphogenesis, they are expressed in unique and overlapping patterns in the prototroch, foot, and mantle. Hsp expression peaked in these tissues during periods of cell differentiation and morphogenesis, returning to lower levels after morphogenesis was complete. These patterns of Hsp and HSF expression in H. asinina are akin to those observed in ecdysozoans and deuterostomes, with Hsps being activated in cells and tissues undergoing morphogenesis.

Building the backbone: the development and evolution of vertebral patterning.

PubMed

Fleming, Angeleen; Kishida, Marcia G; Kimmel, Charles B; Keynes, Roger J

2015-05-15

The segmented vertebral column comprises a repeat series of vertebrae, each consisting of two key components: the vertebral body (or centrum) and the vertebral arches. Despite being a defining feature of the vertebrates, much remains to be understood about vertebral development and evolution. Particular controversy surrounds whether vertebral component structures are homologous across vertebrates, how somite and vertebral patterning are connected, and the developmental origin of vertebral bone-mineralizing cells. Here, we assemble evidence from ichthyologists, palaeontologists and developmental biologists to consider these issues. Vertebral arch elements were present in early stem vertebrates, whereas centra arose later. We argue that centra are homologous among jawed vertebrates, and review evidence in teleosts that the notochord plays an instructive role in segmental patterning, alongside the somites, and contributes to mineralization. By clarifying the evolutionary relationship between centra and arches, and their varying modes of skeletal mineralization, we can better appreciate the detailed mechanisms that regulate and diversify vertebral patterning. © 2015. Published by The Company of Biologists Ltd.

Evolution of vertebrate mechanosensory hair cells and inner ears: toward identifying stimuli that select mutation driven altered morphologies

PubMed Central

Fritzsch, Bernd; Straka, Hans

2014-01-01

Among the major distance senses of vertebrates, the ear is unique in its complex morphological changes during evolution. Conceivably, these changes enable the ear to adapt toward sensing various physically well-characterized stimuli. This review develops a scenario that integrates sensory cell with organ evolution. We propose that molecular and cellular evolution of the vertebrate hair cells occurred prior to the formation of the vertebrate ear. We previously proposed that the genes driving hair cell differentiation, were aggregated in the otic region through developmental re-patterning that generated a unique vertebrate embryonic structure, the otic placode. In agreement with the presence of graviceptive receptors in many vertebrate outgroups, it is likely that the vertebrate ear originally functioned as a simple gravity-sensing organ. Based on the rare occurrence of angular acceleration receptors in vertebrate outgroups, we further propose that the canal system evolved with a more sophisticated ear morphogenesis. This evolving morphogenesis obviously turned the initial otocyst into a complex set of canals and recesses, harboring multiple sensory epithelia each adapted to the acquisition of a specific aspect of a given physical stimulus. As support for this evolutionary progression, we provide several details of the molecular basis of ear development. PMID:24281353

Evolution of the vertebrate claudin gene family: insights from a basal vertebrate, the sea lamprey.

PubMed

Mukendi, Christian; Dean, Nicholas; Lala, Rushil; Smith, Jeramiah; Bronner, Marianne E; Nikitina, Natalya V

2016-01-01

Claudins are major constituents of tight junctions, contributing both to their intercellular sealing and selective permeability properties. While claudins and claudin-like molecules are present in some invertebrates, the association of claudins with tight junctions has been conclusively documented only in vertebrates. Here we report the sequencing, phylogenetic analysis and comprehensive spatiotemporal expression analysis of the entire claudin gene family in the basal extant vertebrate, the sea lamprey. Our results demonstrate that clear orthologues to about half of all mammalian claudins are present in the lamprey, suggesting that at least one round of whole genome duplication contributed to the diversification of this gene family. Expression analysis revealed that claudins are expressed in discrete and specific domains, many of which represent vertebrate-specific innovations, such as in cranial ectodermal placodes and the neural crest; whereas others represent structures characteristic of chordates, e.g. pronephros, notochord, somites, endostyle and pharyngeal arches. By comparing the embryonic expression of claudins in the lamprey to that of other vertebrates, we found that ancestral expression patterns were often preserved in higher vertebrates. Morpholino mediated loss of Cldn3b demonstrated a functional role for this protein in placode and pharyngeal arch morphogenesis. Taken together, our data provide novel insights into the origins and evolution of the claudin gene family and the significance of claudin proteins in the evolution of vertebrates.

Chronic low back pain is associated with reduced vertebral bone mineral measures in community-dwelling adults

PubMed Central

2012-01-01

Background Chronic low back pain (CLBP) experienced in middle-age may have important implications for vertebral bone health, although this issue has not been investigated as a primary aim previously. This study investigated the associations between CLBP and dual energy X-ray absorptiometry (DXA)-derived vertebral bone mineral measures acquired from postero-anterior and lateral-projections, among community-dwelling, middle-aged adults. Methods Twenty-nine adults with CLBP (11 male, 18 female) and 42 adults with no history of LBP in the preceding year (17 male, 25 female) were evaluated. Self-reported demographic and clinical data were collected via questionnaires. Areal bone mineral density (aBMD) was measured in the lumbar spine by DXA. Apparent volumetric (ap.v) BMD in the lumbar spine was also calculated. Multiple linear regression models were used to examine associations between study group (CLBP and control) and vertebral DXA variables by gender, adjusting for height, mass and age. Results There was no difference between groups by gender in anthropometrics or clinical characteristics. In the CLBP group, the mean (SD) duration of CLBP was 13.3 (10.4) years in males and 11.6 (9.9) years in females, with Oswestry Disability Index scores of 16.2 (8.7)% and 15.4 (9.1)%, respectively. Males with CLBP had significantly lower adjusted lateral-projection aBMD and lateral-projection ap.vBMD than controls at L3 with mean differences (standard error) of 0.09 (0.04) g/cm2 (p = 0.03) and 0.02 (0.01) g/cm3 (p = 0.04). These multivariate models accounted for 55% and 53% of the variance in lateral-projection L3 aBMD and lateral-projection L3 ap.vBMD. Conclusions CLBP in males is associated with some lumbar vertebral BMD measures, raising important questions about the mechanism and potential clinical impact of this association. PMID:22458361

Morphogenesis and evolution of vertebrate appendicular muscle

PubMed Central

HAINES, LYNN; CURRIE, PETER D.

2001-01-01

Two different modes are utilised by vertebrate species to generate the appendicular muscle present within fins and limbs. Primitive Chondricthyan or cartilaginous fishes use a primitive mode of muscle formation to generate the muscle of the fins. Direct epithelial myotomal extensions invade the fin and generate the fin muscles while remaining in contact with the myotome. Embryos of amniotes such as chick and mouse use a similar mechanism to that deployed in the bony teleost species, zebrafish. Migratory mesenchymal myoblasts delaminate from fin/limb level somites, migrate to the fin/limb field and differentiate entirely within the context of the fin/limb bud. Migratory fin and limb myoblasts express identical genes suggesting that they possess both morphogenetic and molecular identity. We conclude that the mechanisms controlling tetrapod limb muscle formation arose prior to the Sarcopterygian or tetrapod radiation. PMID:11523824

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

PubMed

Torres, Armando; Torregrosa, Vicens; Marcen, Roberto; Campistol, Josep María; Arias, Manuel; Hernández, Domingo; Fernández, Constantino; Esforzado, Nuria; Paschoalin, Raphael; Pérez, Nuria; García, Ana Isabel; Del Amo, Montserrat; Pomés, Jaume; González Rinne, Ana; Marrero, Domingo; Pérez, Estefanía; Henríquez, Fernando; Díaz, Juan Manuel; Silva, Irene; López, Verónica; Perello, Manuel; Ramos, David; Beneyto, Isabel; Cruzado, José María; Martínez Castelao, Alberto; Bravo, Juan; Rodríguez, Minerva; Díaz, Carmen; Crespo, Josep; Anaya, Fernando; Rodríguez, María Luisa; Cubero, Juan José; Pascual, Pilar; Romero, Rafael; Andrés Belmonte, Amado; Checa, María Dolores; Jiménez, Carlos; Escuin, Fernando; Crespo, Marta; Mir, Marisa; Gómez, Gonzalo; Bayes, Beatriz; González, María José; Gutiérrez, Alex; Cuberes, Marta; Rodríguez Benoit, Alberto; García, Teresa; Llamas, Francisco; Ortega, Agustín; Conde, José Luis; Gómez Alamillo, Carlos

2016-01-01

The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Developmental mechanisms of intervertebral disc and vertebral column formation.

PubMed

Lawson, Lisa Y; Harfe, Brian D

2017-11-01

The vertebral column consists of repeating units of ossified vertebrae that are adjoined by fibrocartilagenous intervertebral discs. These structures form from the embryonic notochord and somitic mesoderm. In humans, congenital malformations of the vertebral column include scoliosis, kyphosis, spina bifida, and Klippel Feil syndrome. In adulthood, a common malady affecting the vertebral column includes disc degeneration and associated back pain. Indeed, recent reports estimate that low back pain is the number one cause of disability worldwide. Our review provides an overview of the molecular mechanisms underlying vertebral column morphogenesis and intervertebral disc development and maintenance, with an emphasis on what has been gleaned from recent genetic studies in mice. The aim of this review is to provide a developmental framework through which vertebral column formation can be understood so that ultimately, research scientists and clinicians alike can restore disc health with appropriately designed gene and cell-based therapies. WIREs Dev Biol 2017, 6:e283. doi: 10.1002/wdev.283 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Aboveground vertebrate and invertebrate herbivore impact on net N mineralization in subalpine grasslands.

PubMed

Risch, Anita C; Schotz, Martin; Vandegehuchte, Martijn L; Van Der Putten, Wim H; Duyts, Henk; Raschein, Ursina; Gwiazdowicz, Dariusz J; Busse, Matt D; Page-dumroese, Deborah S; Zimmermann, Stephan

2015-12-01

Aboveground herbivores have strong effects on grassland nitrogen (N) cycling. They can accelerate or slow down soil net N mineralization depending on ecosystem productivity and grazing intensity. Yet, most studies only consider either ungulates or invertebrate herbivores, but not the combined effect of several functionally different vertebrate and invertebrate herbivore species or guilds. We assessed how a diverse herbivore community affects net N mineralization in subalpine grasslands. By using size-selective fences, we progressively excluded large, medium, and small mammals, as well as invertebrates from two vegetation types, and assessed how the exclosure types (ET) affected net N mineralization. The two vegetation types differed in long-term management (centuries), forage quality, and grazing history and intensity. To gain a more mechanistic understanding of how herbivores affect net N mineralization, we linked mineralization to soil abiotic (temperature; moisture; NO3-, NH4+, and total inorganic N concentrations/pools; C, N, P concentrations; pH; bulk density), soil biotic (microbial biomass; abundance of collembolans, mites, and nematodes) and plant (shoot and root biomass; consumption; plant C, N, and fiber content; plant N pool) properties. Net N mineralization differed between ET, but not between vegetation types. Thus, short-term changes in herbivore community composition and, therefore, in grazing intensity had a stronger effect on net N mineralization than long-term management and grazing history. We found highest N mineralization values when only invertebrates were present, suggesting that mammals had a negative effect on net N mineralization. Of the variables included in our analyses, only mite abundance and aboveground plant biomass explained variation in net N mineralization among ET. Abundances of both mites and leaf-sucking invertebrates were positively correlated with aboveground plant biomass, and biomass increased with progressive exclusion

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

Subsequent Vertebral Fractures Post Cement Augmentation of the Thoracolumbar Spine: Does it Correlate With Level-specific Bone Mineral Density Scores?

PubMed

Hey, Hwee Weng Dennis; Hwee Weng, Dennis Hey; Tan, Jun Hao; Jun, Hao Tan; Tan, Chuen Seng; Chuen, Seng Tan; Tan, Hsi Ming Bryan; Ming, Bryan Tan Hsi; Lau, Puang Huh Bernard; Huh, Bernard Lau Puang; Hee, Hwan Tak; Hwan, Tak Hee

2015-12-01

A case-control study. In this study, we investigated the correlation between level-specific preoperative bone mineral density and subsequent vertebral fractures. We also identified factors associated with subsequent vertebral fractures. Complications of cement augmentation of the spine include subsequent vertebral fractures, leading to unnecessary morbidity and more treatment. Ability to predict at-risk vertebra will help guide management. We studied all patients with osteoporotic compression fractures who underwent cement augmentation in a single institution from November 2001 to December 2010 by a single surgeon. Association between level-specific bone mineral density T-scores and subsequent fractures was assessed. Multivariable analysis was performed to identify significant factors associated with subsequent vertebral fractures. 93 patients followed up for a mean duration of 25.1 months (12-96) had a mean age of 76.8 years (47-99). Vertebroplasty was performed in 58 patients (62.4%) on 68 levels and kyphoplasty in 35 patients (37.6%) on 44 levels. Refracture was seen in 16 patients (17.2%). The time to subsequent fracture post cement augmentation was 20.5 months (2-90). For refracture cases, 43.8% (7/16) fractured in the adjacent vertebrae. Subsequently fractured vertebra had a mean T-score of -2.860 (95% confidence interval -3.268 to -2.452) and nonfractured vertebra had a mean T-score of -2.180 (95% confidence interval -2.373 to -1.986). A T-score of -2.2 or lower is predictive of refracture at that vertebra (P = 0.047). Odds ratio increases with decreasing T-scores from -2.2 or lower to -2.6 or lower. A T-score of -2.6 or lower gives no additional predictive advantage. After multivariable analysis, age (P = 0.049) and loss of preoperative anterior vertebral height (P = 0.017) are associated with refracture. Level-specific T-scores are predictive of subsequent fractures and the odds ratio increases with lower T-scores from -2.2 or less to -2.6 or less. They

Synthetic Morphogenesis.

PubMed

Teague, Brian P; Guye, Patrick; Weiss, Ron

2016-09-01

Throughout biology, function is intimately linked with form. Across scales ranging from subcellular to multiorganismal, the identity and organization of a biological structure's subunits dictate its properties. The field of molecular morphogenesis has traditionally been concerned with describing these links, decoding the molecular mechanisms that give rise to the shape and structure of cells, tissues, organs, and organisms. Recent advances in synthetic biology promise unprecedented control over these molecular mechanisms; this opens the path to not just probing morphogenesis but directing it. This review explores several frontiers in the nascent field of synthetic morphogenesis, including programmable tissues and organs, synthetic biomaterials and programmable matter, and engineering complex morphogenic systems de novo. We will discuss each frontier's objectives, current approaches, constraints and challenges, and future potential. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

Tracing the evolutionary origin of vertebrate skeletal tissues: insights from cephalochordate amphioxus.

PubMed

Yong, Luok Wen; Yu, Jr-Kai

2016-08-01

Vertebrate mineralized skeletal tissues are widely considered as an evolutionary novelty. Despite the importance of these tissues to the adaptation and radiation of vertebrate animals, the evolutionary origin of vertebrate skeletal tissues remains largely unclear. Cephalochordates (Amphioxus) occupy a key phylogenetic position and can serve as a valuable model for studying the evolution of vertebrate skeletal tissues. Here we summarize recent advances in amphioxus developmental biology and comparative genomics that can help to elucidate the evolutionary origins of the vertebrate skeletal tissues and their underlying developmental gene regulatory networks (GRN). By making comparisons to the developmental studies in vertebrate models and recent discoveries in paleontology and genomics, it becomes evident that the collagen matrix-based connective tissues secreted by the somite-derived cells in amphioxus likely represent the rudimentary skeletal tissues in chordates. We propose that upon the foundation of this collagenous precursor, novel tissue mineralization genes that arose from gene duplications were incorporated into an ancestral mesodermal GRN that makes connective and supporting tissues, leading to the emergence of highly-mineralized skeletal tissues in early vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of QCT Bone Mineral Density and Bone Structure With Vertebral Fractures in Patients With Multiple Myeloma.

PubMed

Borggrefe, Jan; Giravent, Sarah; Thomsen, Felix; Peña, Jaime; Campbell, Graeme; Wulff, Asmus; Günther, Andreas; Heller, Martin; Glüer, Claus C

2015-07-01

Computed tomography (CT) is used for staging osteolytic lesions and detecting fractures in patients with multiple myeloma (MM). In the OsteoLysis of Metastases and Plasmacell-infiltration Computed Tomography 2 study (OLyMP-CT) study we investigated whether patients with and without vertebral fractures show differences in bone mineral density (BMD) or microstructure that could be used to identify patients at risk for fracture. We evaluated whole-body CT scans in a group of 104 MM patients without visible osteolytic lesions using an underlying lightweight calibration phantom (Image Analysis Inc., Columbia, KY, USA). QCT software (StructuralInsight) was used for the assessment of BMD and bone structure of the T11 or T12 vertebral body. Age-adjusted standardized odds ratios (sORs) per SD change were derived from logistic regression analyses, and areas under the receiver operating characteristics (ROC) curve (AUCs) analyses were calculated. Forty-six of the 104 patients had prevalent vertebral fractures (24/60 men, 22/44 women). Patients with fractures were not significantly older than patients without fractures (mean ± SD, 64 ± 9.2 versus 62 ± 12.3 years; p = 0.4). Trabecular BMD in patients with fractures versus without fractures was 169 ± 41 versus 192 ± 51 mg/cc (AUC = 0.62 ± 0.06, sOR = 1.6 [1.1 to 2.5], p = 0.02). Microstructural variables achieved optimal discriminatory power at bone thresholds of 150 mg/cc. Best fracture discrimination for single microstructural variables was observed for trabecular separation (Tb.Sp) (AUC = 0.72 ± 0.05, sOR = 2.4 (1.5 to 3.9), p < 0.0001). In multivariate models AUCs improved to 0.77 ± 0.05 for BMD and Tb.Sp, and 0.79 ± 0.05 for Tb.Sp and trabecular thickness (Tb.Th). Compared to BMD values, these improvements of AUC values were statistically significant (p < 0.0001). In MM patients, QCT-based analyses of bone structure derived from routine CT

Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect.

PubMed

Fujishiro, Takaaki; Bauer, Thomas W; Kobayashi, Naomi; Kobayashi, Hideo; Sunwoo, Moon Hae; Seim, Howard B; Turner, A Simon

2007-09-01

Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model.

In vivo genome-wide analysis of multiple tissues identifies gene regulatory networks, novel functions and downstream regulatory genes for Bapx1 and its co-regulation with Sox9 in the mammalian vertebral column.

PubMed

Chatterjee, Sumantra; Sivakamasundari, V; Yap, Sook Peng; Kraus, Petra; Kumar, Vibhor; Xing, Xing; Lim, Siew Lan; Sng, Joel; Prabhakar, Shyam; Lufkin, Thomas

2014-12-05

Vertebrate organogenesis is a highly complex process involving sequential cascades of transcription factor activation or repression. Interestingly a single developmental control gene can occasionally be essential for the morphogenesis and differentiation of tissues and organs arising from vastly disparate embryological lineages. Here we elucidated the role of the mammalian homeobox gene Bapx1 during the embryogenesis of five distinct organs at E12.5 - vertebral column, spleen, gut, forelimb and hindlimb - using expression profiling of sorted wildtype and mutant cells combined with genome wide binding site analysis. Furthermore we analyzed the development of the vertebral column at the molecular level by combining transcriptional profiling and genome wide binding data for Bapx1 with similarly generated data sets for Sox9 to assemble a detailed gene regulatory network revealing genes previously not reported to be controlled by either of these two transcription factors. The gene regulatory network appears to control cell fate decisions and morphogenesis in the vertebral column along with the prevention of premature chondrocyte differentiation thus providing a detailed molecular view of vertebral column development.

Establishment of the Vertebrate Germ Layers.

PubMed

Tseng, Wei-Chia; Munisha, Mumingjiang; Gutierrez, Juan B; Dougan, Scott T

2017-01-01

The process of germ layer formation is a universal feature of animal development. The germ layers separate the cells that produce the internal organs and tissues from those that produce the nervous system and outer tissues. Their discovery in the early nineteenth century transformed embryology from a purely descriptive field into a rigorous scientific discipline, in which hypotheses could be tested by observation and experimentation. By systematically addressing the questions of how the germ layers are formed and how they generate overall body plan, scientists have made fundamental contributions to the fields of evolution, cell signaling, morphogenesis, and stem cell biology. At each step, this work was advanced by the development of innovative methods of observing cell behavior in vivo and in culture. Here, we take an historical approach to describe our current understanding of vertebrate germ layer formation as it relates to the long-standing questions of developmental biology. By comparing how germ layers form in distantly related vertebrate species, we find that highly conserved molecular pathways can be adapted to perform the same function in dramatically different embryonic environments.

Prospective evaluation of risk of vertebral fractures using quantitative ultrasound measurements and bone mineral density in a population-based sample of postmenopausal women: results of the Basel Osteoporosis Study.

PubMed

Hollaender, R; Hartl, F; Krieg, M-A; Tyndall, A; Geuckel, C; Buitrago-Tellez, C; Manghani, M; Kraenzlin, M; Theiler, R; Hans, D

2009-03-01

Prospective studies have shown that quantitative ultrasound (QUS) techniques predict the risk of fracture of the proximal femur with similar standardised risk ratios to dual-energy x-ray absorptiometry (DXA). Few studies have investigated these devices for the prediction of vertebral fractures. The Basel Osteoporosis Study (BOS) is a population-based prospective study to assess the performance of QUS devices and DXA in predicting incident vertebral fractures. 432 women aged 60-80 years were followed-up for 3 years. Incident vertebral fractures were assessed radiologically. Bone measurements using DXA (spine and hip) and QUS measurements (calcaneus and proximal phalanges) were performed. Measurements were assessed for their value in predicting incident vertebral fractures using logistic regression. QUS measurements at the calcaneus and DXA measurements discriminated between women with and without incident vertebral fracture, (20% height reduction). The relative risks (RRs) for vertebral fracture, adjusted for age, were 2.3 for the Stiffness Index (SI) and 2.8 for the Quantitative Ultrasound Index (QUI) at the calcaneus and 2.0 for bone mineral density at the lumbar spine. The predictive value (AUC (95% CI)) of QUS measurements at the calcaneus remained highly significant (0.70 for SI, 0.72 for the QUI, and 0.67 for DXA at the lumbar spine) even after adjustment for other confounding variables. QUS of the calcaneus and bone mineral density measurements were shown to be significant predictors of incident vertebral fracture. The RRs for QUS measurements at the calcaneus are of similar magnitude as for DXA measurements.

Oligomerization-Dependent Regulation of Motility and Morphogenesis by the Collagen Xviii Nc1/Endostatin Domain

PubMed Central

Kuo, Calvin J.; LaMontagne, Kenneth R.; Garcia-Cardeña, Guillermo; Ackley, Brian D.; Kalman, Daniel; Park, Susan; Christofferson, Rolf; Kamihara, Junne; Ding, Yuan-Hua; Lo, Kin-Ming; Gillies, Stephen; Folkman, Judah; Mulligan, Richard C.; Javaherian, Kashi

2001-01-01

Collagen XVIII (c18) is a triple helical endothelial/epithelial basement membrane protein whose noncollagenous (NC)1 region trimerizes a COOH-terminal endostatin (ES) domain conserved in vertebrates, Caenorhabditis elegans and Drosophila. Here, the c18 NC1 domain functioned as a motility-inducing factor regulating the extracellular matrix (ECM)-dependent morphogenesis of endothelial and other cell types. This motogenic activity required ES domain oligomerization, was dependent on rac, cdc42, and mitogen-activated protein kinase, and exhibited functional distinction from the archetypal motogenic scatter factors hepatocyte growth factor and macrophage stimulatory protein. The motility-inducing and mitogen-activated protein kinase–stimulating activities of c18 NC1 were blocked by its physiologic cleavage product ES monomer, consistent with a proteolysis-dependent negative feedback mechanism. These data indicate that the collagen XVIII NC1 region encodes a motogen strictly requiring ES domain oligomerization and suggest a previously unsuspected mechanism for ECM regulation of motility and morphogenesis. PMID:11257123

Continuous light affects mineralization and delays osteoid incorporation in vertebral bone of Atlantic salmon (Salmo salar L.).

PubMed

Wargelius, Anna; Fjelldal, Per Gunnar; Nordgarden, Ulla; Hansen, Tom

2009-03-01

In order to study the effects of photoperiod on fish bone, Atlantic salmon (Salmo salar L.) were exposed to two light regimes (natural and continuous light) from January until June. During the experimental period, several parameters related to the inorganic (minerals) and organic (osteoid) phases were measured. Changes in the organic phase were related to mechanical strength (yield-load) and the expression of the genes sonic hedgehog (shh) and collagen type I alpha 2 (col I). Co-variation between yield-load and the expression of both shh and col I were detected in both groups. It was also shown that fish on the continuous light regime had delayed activation of osteoid incorporation. Mineralization properties were measured with stiffness, mineral incorporation per day and expression of alkaline phosphatase (alp) and matrix Gla protein (mgp). Stiffness, mineral incorporation and gene expression followed the same trend in both light groups in late spring, whereas an increase in the expression of mgp and alp was detected in April, followed by significantly higher stiffness at last sampling in both light groups. These results indicate that constant light affects mineralization and delays osteoid incorporation in Atlantic salmon during the spring. However, in this experiment light treatment did not promote the development of vertebral deformities. Our results also suggest that shh can be used as a marker of osteoblast proliferation and col I a marker of osteoid incorporation, and that both alp and mgp expression could be associated with a rapid increase in mineralization in Atlantic salmon vertebrae.

Mineral-related proteins of sea urchin teeth: Lytechinus variegatus.

PubMed

Veis, Arthur; Barss, Joseph; Dahl, Thomas; Rahima, Mohammed; Stock, Stuart

2002-12-01

Sea urchins have a set of five continuously growing teeth, each of which has a very complex structure. The mineral phase is calcite of varying Mg content, depending on the location within a tooth. The calcium carbonate is present in amorphous, plate-like and rod-like forms. It has been hypothesized that the mineral deposition is a matrix-mediated process, similar to that in vertebrate bone and tooth, wherein certain macromolecules within the organic matrix of the mineralized tissue play an important role in nucleating and controlling the growth habit of the mineral crystals. It has also been hypothesized that the mineral-related macromolecules involved in urchin teeth might bear a direct evolutionary relationship to those of the vertebrate tooth. These hypotheses are explored here by examining the pattern and nature of the mineral distribution, using microCT of intact teeth, and the nature of the mineral-related matrix proteins. The mineral-related proteins were extracted and fractionated by anion exchange chromatography. The relationship of certain fractions to vertebrate matrix proteins was established by immunoblots using antibodies to vertebrate tooth proteins. The antibodies were then used to localize the proteins within the teeth, by immunocytochemistry and histology with specific staining. The microCT data on mineral density has been correlated with the patterns of cellular migration and mineral deposition within the tooth as it grows. It appears that the mineralization within the different tooth compartments might take place under the influence of different matrix proteins. Further studies are in progress to more completely describe the vertebrate-invertebrate immunologically cross-reactive proteins of the urchin teeth. Copyright 2002 Wiley-Liss, Inc.

Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs.

PubMed

Cummings, Steven R; Karpf, David B; Harris, Fran; Genant, Harry K; Ensrud, Kristine; LaCroix, Andrea Z; Black, Dennis M

2002-03-01

To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.

Coordinating cell and tissue behavior during zebrafish neural tube morphogenesis.

PubMed

Araya, Claudio; Ward, Laura C; Girdler, Gemma C; Miranda, Miguel

2016-03-01

The development of a vertebrate neural epithelium with well-organized apico-basal polarity and a central lumen is essential for its proper function. However, how this polarity is established during embryonic development and the potential influence of surrounding signals and tissues on such organization has remained less understood. In recent years the combined superior transparency and genetics of the zebrafish embryo has allowed for in vivo visualization and quantification of the cellular and molecular dynamics that govern neural tube structure. Here, we discuss recent studies revealing how co-ordinated cell-cell interactions coupled with adjacent tissue dynamics are critical to regulate final neural tissue architecture. Furthermore, new findings show how the spatial regulation and timing of orientated cell division is key in defining precise lumen formation at the tissue midline. In addition, we compare zebrafish neurulation with that of amniotes and amphibians in an attempt to understand the conserved cellular mechanisms driving neurulation and resolve the apparent differences among animals. Zebrafish neurulation not only offers fundamental insights into early vertebrate brain development but also the opportunity to explore in vivo cell and tissue dynamics during complex three-dimensional animal morphogenesis. © 2015 Wiley Periodicals, Inc.

Osteolytic and mixed cancer metastasis modulates collagen and mineral parameters within rat vertebral bone matrix.

PubMed

Burke, Mikhail V; Atkins, Ayelet; Akens, Margarete; Willett, Thomas L; Whyne, Cari M

2016-12-01

Metastatic involvement in vertebral bone diminishes the mechanical integrity of the spine; however minimal data exist on the potential impact of metastases on the intrinsic material characteristics of the bone matrix. Thirty-four (34) female athymic rats were inoculated with HeLa (N = 17) or Ace-1 (N = 17) cancer cells lines producing osteolytic or mixed (osteolytic and osteoblastic) metastases, respectively. A maximum of 21 days was allowed between inoculation and rat sacrifice for vertebrae extraction. High performance liquid chromatography (HPLC) was utilized to determine modifications in collagen-I parameters such as proline hydroxylation and the formation of specific enzymatic and non-enzymatic (pentosidine) cross-links. Raman spectroscopy was used to determine relative changes in mineral crystallinity, mineral carbonation, mineral/collagen matrix ratio, collagen quality ratio, and proline hydroxylation. HPLC results showed significant increase in the formation of pentosidine and decrease in the formation of the enzymatic cross-link deoxy-pryridinoline within osteolytic bone compared to mixed bone. Raman results showed decreased crystallinity, increased carbonation, and collagen quality (aka 1660/1690 sub-band) ratio with osteolytic bone compared to mixed bone and healthy controls along with an observed increase in proline hydroxylation with metastatic involvement. The mineral/matrix ratio decreased in both osteolytic and mixed bone compared to healthy controls. Quantifying modifications within the intrinsic characteristics of bone tissue will provide a foundation to assess the impact of current therapies on the material behavior of bone tissue in the metastatic spine and highlight targets for the development of new therapeutics and approaches for treatment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2126-2136, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Cooption of secretory phospholipase (SPLA2) for different aspects of gravity receptor-associated mineralization in vertebrate phylogeny

NASA Astrophysics Data System (ADS)

Thalmann, R.; Lu, W.

2009-04-01

Vertebrate gravity-associated minerals consists of either a single large stone (otolith), or an assembly of minute biomineral particles, otoconia ("ear dust"). Otoliths and both, amphibian and reptilian otoconia, consist of aragonite, whereas avian and mammalian otoconia consist of calcite. Vertebrate gravity-associated minerals are the product of site-directed biologically-controlled mineralization. Insoluble frame work molecules specify sites of nucleation and direction of crystal growth. Soluble matrix proteins modulate growth kinetics and crystal morphology. It is most remarkable that the principal insoluble frame work protein, otolin, is the same for both, otolith and otoconia. Otolin is a novel type of collagen, homologous to the network-forming collagen type X prevalent in mature chondrocytes. The principal soluble matrix proteins of calcitic, aragonitic, and most likely also of vateritic otoconia are all homologs of SPLA2, which is most prevalent in pancreatic secretion and snake venoms. Otonin90 (OC90), the principal soluble matrix protein of calcitic otoconia consists of two SPLA-like (SPLAL) domains, which are connected by a sizeable linker segment and contain significant terminal extensions. The MW of the protein backbone amounts to approximately 50 kDa. The molecule contains, in addition massive post-translational modifications, 80% of which are accounted for by sulfated GAGs, resulting in a total MW of 100 KDa. The protein backbone is moderately acidic, pI 4.4, but the pI of the whole molecule is 2.9, indicating a substantial acidity of the GAG component. In adapting SPLA2 for mineral modulation the enzymatic site is modified and presumed nonfunctional. The seven SH- bonds are rigorously conserved in both, OC90 and otoconin22 (OC22). It appears that the SH-bonds of the parent SPLA2 are intended to stabilize the molecule to ensure continued enzymatic activity in the hostile environment of the gut. It therefore seems logical that SPLA2 was coopted for

Muscle contraction controls skeletal morphogenesis through regulation of chondrocyte convergent extension.

PubMed

Shwartz, Yulia; Farkas, Zsuzsanna; Stern, Tomer; Aszódi, Attila; Zelzer, Elazar

2012-10-01

Convergent extension driven by mediolateral intercalation of chondrocytes is a key process that contributes to skeletal growth and morphogenesis. While progress has been made in deciphering the molecular mechanism that underlies this process, the involvement of mechanical load exerted by muscle contraction in its regulation has not been studied. Using the zebrafish as a model system, we found abnormal pharyngeal cartilage morphology in both chemically and genetically paralyzed embryos, demonstrating the importance of muscle contraction for zebrafish skeletal development. The shortening of skeletal elements was accompanied by prominent changes in cell morphology and organization. While in control the cells were elongated, chondrocytes in paralyzed zebrafish were smaller and exhibited a more rounded shape, confirmed by a reduction in their length-to-width ratio. The typical columnar organization of cells was affected too, as chondrocytes in various skeletal elements exhibited abnormal stacking patterns, indicating aberrant intercalation. Finally, we demonstrate impaired chondrocyte intercalation in growth plates of muscle-less Sp(d) mouse embryos, implying the evolutionary conservation of muscle force regulation of this essential morphogenetic process.Our findings provide a new perspective on the regulatory interaction between muscle contraction and skeletal morphogenesis by uncovering the role of muscle-induced mechanical loads in regulating chondrocyte intercalation in two different vertebrate models. Copyright © 2012 Elsevier Inc. All rights reserved.

Computerized tomographic determination of spinal bone mineral content

NASA Technical Reports Server (NTRS)

Cann, C. E.; Genant, H. K.

1980-01-01

The aims of the study were three-fold: to determine the magnitude of vertebral cancellous mineral loss in normal subjects during bedrest, to compare this loss with calcium balance and mineral loss in peripheral bones, and to use the vertebral measurements as an evaluative criterion for the C12MDP treatment and compare it with other methods. The methods used are described and the results from 14 subjects are presented.

Zebrafish zic2 controls formation of periocular neural crest and choroid fissure morphogenesis.

PubMed

Sedykh, Irina; Yoon, Baul; Roberson, Laura; Moskvin, Oleg; Dewey, Colin N; Grinblat, Yevgenya

2017-09-01

The vertebrate retina develops in close proximity to the forebrain and neural crest-derived cartilages of the face and jaw. Coloboma, a congenital eye malformation, is associated with aberrant forebrain development (holoprosencephaly) and with craniofacial defects (frontonasal dysplasia) in humans, suggesting a critical role for cross-lineage interactions during retinal morphogenesis. ZIC2, a zinc-finger transcription factor, is linked to human holoprosencephaly. We have previously used morpholino assays to show zebrafish zic2 functions in the developing forebrain, retina and craniofacial cartilage. We now report that zebrafish with genetic lesions in zebrafish zic2 orthologs, zic2a and zic2b, develop with retinal coloboma and craniofacial anomalies. We demonstrate a requirement for zic2 in restricting pax2a expression and show evidence that zic2 function limits Hh signaling. RNA-seq transcriptome analysis identified an early requirement for zic2 in periocular neural crest as an activator of alx1, a transcription factor with essential roles in craniofacial and ocular morphogenesis in human and zebrafish. Collectively, these data establish zic2 mutant zebrafish as a powerful new genetic model for in-depth dissection of cell interactions and genetic controls during craniofacial complex development. Copyright © 2017 Elsevier Inc. All rights reserved.

Roles for FGF in lamprey pharyngeal pouch formation and skeletogenesis highlight ancestral functions in the vertebrate head.

PubMed

Jandzik, David; Hawkins, M Brent; Cattell, Maria V; Cerny, Robert; Square, Tyler A; Medeiros, Daniel M

2014-02-01

A defining feature of vertebrates (craniates) is a pronounced head supported and protected by a cellularized endoskeleton. In jawed vertebrates (gnathostomes), the head skeleton is made of rigid three-dimensional elements connected by joints. By contrast, the head skeleton of modern jawless vertebrates (agnathans) consists of thin rods of flexible cellular cartilage, a condition thought to reflect the ancestral vertebrate state. To better understand the origin and evolution of the gnathostome head skeleton, we have been analyzing head skeleton development in the agnathan, lamprey. The fibroblast growth factors FGF3 and FGF8 have various roles during head development in jawed vertebrates, including pharyngeal pouch morphogenesis, patterning of the oral skeleton and chondrogenesis. We isolated lamprey homologs of FGF3, FGF8 and FGF receptors and asked whether these functions are ancestral features of vertebrate development or gnathostome novelties. Using gene expression and pharmacological agents, we found that proper formation of the lamprey head skeleton requires two phases of FGF signaling: an early phase during which FGFs drive pharyngeal pouch formation, and a later phase when they directly regulate skeletal differentiation and patterning. In the context of gene expression and functional studies in gnathostomes, our results suggest that these roles for FGFs arose in the first vertebrates and that the evolution of the jaw and gnathostome cellular cartilage was driven by changes developmentally downstream from pharyngeal FGF signaling.

Integration of planar cell polarity and ECM signaling in elongation of the vertebrate body plan.

PubMed

Skoglund, Paul; Keller, Ray

2010-10-01

The shaping of the vertebrate embryonic body plan depends heavily on the narrowing and lengthening (convergence and extension) of embryonic tissues by cell intercalation, a process by which cells actively crawl between one another along the axis of convergence to produce a narrower, longer array. We discuss recent evidence that the vertebrate non-canonical Wnt/Planar Cell Polarity (PCP) pathway, known to directly function in polarizing the movements of intercalating cells, is also involved in the localized assembly of extracellular matrix (ECM). These cell-ECM interactions, in turn, are necessary for expression of the oriented, polarized cell intercalation. The mechanism of PCP/ECM interactions, their molecular signaling, and their mechanical consequences for morphogenesis are discussed with the goal of identifying important unsolved issues. Copyright © 2010 Elsevier Ltd. All rights reserved.

Identifying osteoporotic vertebral endplate and cortex fractures

PubMed Central

Santiago, Fernando Ruiz; Deng, Min; Nogueira-Barbosa, Marcello H.

2017-01-01

Osteoporosis is the most common metabolic bone disease, and vertebral fractures (VFs) are the most common osteoporotic fracture. A single atraumatic VF may lead to the diagnosis of osteoporosis. Prevalent VFs increase the risk of future vertebral and non-vertebral osteoporotic fracture independent of bone mineral density (BMD). The accurate and clear reporting of VF is essential to ensure patients with osteoporosis receive appropriate treatment. Radiologist has a vital role in the diagnosis of this disease. Several morphometrical and radiological methods for detecting osteoporotic VF have been proposed, but there is no consensus regarding the definition of osteoporotic VF. A vertebra may fracture yet not ever result in measurable changes in radiographic height or area. To overcome these difficulties, algorithm-based qualitative approach (ABQ) was developed with a focus on the identification of change in the vertebral endplate. Evidence of endplate fracture (rather than variation in vertebral shape) is the primary indicator of osteoporotic fracture according to ABQ criteria. Other changes that may mimic osteoporotic fractures should be systemically excluded. It is also possible that vertebral cortex fracture may not initially occur in endplate. Particularly, vertebral cortex fracture can occur in anterior vertebral cortex without gross vertebral deformity (VD), or fractures deform the anterior vertebral cortex without endplate disruption. This article aims to serve as a teaching material for physicians or researchers to identify vertebral endplate/cortex fracture (ECF). Emphasis is particularly dedicated to identifying ECF which may not be associated apparent vertebral body collapse. We believe a combined approach based on standardized radiologic evaluation by experts and morphometry measurement is the most appropriate approach to detect and classify VFs. PMID:29184768

Apical constriction: themes and variations on a cellular mechanism driving morphogenesis

PubMed Central

Martin, Adam C.; Goldstein, Bob

2014-01-01

Apical constriction is a cell shape change that promotes tissue remodeling in a variety of homeostatic and developmental contexts, including gastrulation in many organisms and neural tube formation in vertebrates. In recent years, progress has been made towards understanding how the distinct cell biological processes that together drive apical constriction are coordinated. These processes include the contraction of actin-myosin networks, which generates force, and the attachment of actin networks to cell-cell junctions, which allows forces to be transmitted between cells. Different cell types regulate contractility and adhesion in unique ways, resulting in apical constriction with varying dynamics and subcellular organizations, as well as a variety of resulting tissue shape changes. Understanding both the common themes and the variations in apical constriction mechanisms promises to provide insight into the mechanics that underlie tissue morphogenesis. PMID:24803648

Vertebral Fractures and Bone Mineral Density in Patients With Idiopathic Hypoparathyroidism on Long-Term Follow-Up.

PubMed

Chawla, Himika; Saha, Soma; Kandasamy, Devasenathipathy; Sharma, Raju; Sreenivas, Vishnubhatla; Goswami, Ravinder

2017-01-01

Bone mineral density (BMD) is increased in idiopathic hypoparathyroidism (IH). Parathyroid hormone (PTH) deficiency, hypocalcemic seizures, and anticonvulsants could compromise skeletal health in IH. We assessed vertebral fractures (VFs) and related factors in IH and change in BMD during follow-up. VFs were assessed by morphometry. BMD was assessed by dual-energy X-ray absorptiometery at the lumbar spine, hip, and forearm. Change in BMD was assessed in a subset after a 10-year follow-up. The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Included were 104 patients with IH and 64 healthy controls. Hypocalcemia, hyperphosphatemia, normal kidney function, and low serum PTH levels were used to diagnose IH. VFs were seen in 18.3% of patients with IH and 4.7% of controls (odds ratio, 4.54; 95% confidence interval, 1.28 to 16.04). Use of anticonvulsants and menopause were significantly associated (P < 0.05) with VF. Mean BMD at lumbar spine and hip were higher by 21.4% and 8.6%, respectively, in IH than in controls (P < 0.001), respectively. BMD significantly increased during follow-up at all sites. Change in BMD correlated with maintenance of the serum calcium/phosphorus ratio during follow-up. Despite increased BMD, prevalence of vertebral-fractures is greater in patients with IH, especially in postmenopausal women and those on anticonvulsant therapy. Copyright © 2017 by the Endocrine Society

Extracellular matrix motion and early morphogenesis

PubMed Central

Loganathan, Rajprasad; Rongish, Brenda J.; Smith, Christopher M.; Filla, Michael B.; Czirok, Andras; Bénazéraf, Bertrand

2016-01-01

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale ‘total’ cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. PMID:27302396

Vertebral Development in Paleozoic and Mesozoic Tetrapods Revealed by Paleohistological Data

PubMed Central

Danto, Marylène; Witzmann, Florian; Fröbisch, Nadia B.

2016-01-01

Basal tetrapods display a wide spectrum of vertebral centrum morphologies that can be used to distinguish different tetrapod groups. The vertebral types range from multipartite centra in stem-tetrapods, temnospondyls, and seymouriamorphs up to monospondylous centra in lepospondyls and have been drawn upon for reconstructing major evolutionary trends in tetrapods that are now considered textbook knowledge. Two modes of vertebral formation have been postulated: the multipartite vertebrae formed first as cartilaginous elements with subsequent ossification. The monospondylous centrum, in contrast, was formed by direct ossification without a cartilaginous precursor. This study describes centrum morphogenesis in basal tetrapods for the first time, based on bone histology. Our results show that the intercentra of the investigated stem-tetrapods consist of a small band of periosteal bone and a dense network of endochondral bone. In stereospondyl temnospondyls, high amounts of calcified cartilage are preserved in the endochondral trabeculae. Notably, the periosteal region is thickened and highly vascularized in the plagiosaurid stereospondyls. Among “microsaur” lepospondyls, the thickened periosteal region is composed of compact bone and the notochordal canal is surrounded by large cell lacunae. In nectridean lepospondyls, the periosteal region has a spongy structure with large intertrabecular spaces, whereas the endochondral region has a highly cancellous structure. Our observations indicate that regardless of whether multipartite or monospondylous, the centra of basal tetrapods display first endochondral and subsequently periosteal ossification. A high interspecific variability is observed in growth rate, organization, and initiation of periosteal ossification. Moreover, vertebral development and structure reflect different lifestyles. The bottom-dwelling Plagiosauridae increase their skeletal mass by hyperplasy of the periosteal region. In nectrideans, the skeletal

Thyroid dysfunction in an adult female population: A population-based study of Latin American Vertebral Osteoporosis Study (LAVOS) - Puerto Rico site.

PubMed

González-Rodríguez, Loida A; Felici-Giovanini, Marcos E; Haddock, Lillian

2013-06-01

To determine the prevalence of hypothyroidism in an adult female population in Puerto Rico and to determine the relationship between hypothyroidism, bone mineral density and vertebral and non-vertebral fractures in this population. Data from the 400 subjects' database of the Latin American Vertebral Osteoporosis Study (LAVOS), Puerto Rico site was reviewed. Patient's medical history, anthropometric data, current medications, laboratories, and DXA results was extracted. Subjects with thyroid dysfunction were identified based on their previous medical history and levels of TSH. Bone Mineral Density was classified using the World Health Organization criteria. Crude prevalence of thyroid dysfunction were estimated with a confidence of 95% and weighted by the population distribution by age, according to the distribution by age group in the 2000 census. Bone mineral densities and prevalence of vertebral and non-vertebral fractures were compared among the groups. The weighted prevalence of hyperthyroidism in this population was 0.0043% (95% CI: -0.0021%, 0.0107%). The weighted prevalence of hypothyroidism was 24.2% (95% CI: 19.9%, 28.4%). Increased prevalence of hypothyroidism was found in participants 70 years or older. The mean BMD at spine, hip and femoral neck was similar among the groups. No difference in the proportion of participants with vertebral and non-vertebral fractures was found among the groups. Our study found a high prevalence of hypothyroidism among adult postmenopausal females in Puerto Rico. No association between hypothyroidism and decreased bone mineral densities, vertebral or non-vertebral fractures was found in this population.

Gout and the Risk of Non-vertebral Fracture.

PubMed

Kim, Seoyoung C; Paik, Julie M; Liu, Jun; Curhan, Gary C; Solomon, Daniel H

2017-02-01

fracture. Among patients with gout, sUA was not associated with the risk of non-vertebral fracture. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

Role of cranial neural crest cells in visceral arch muscle positioning and morphogenesis in the Mexican axolotl, Ambystoma mexicanum.

PubMed

Ericsson, Rolf; Cerny, Robert; Falck, Pierre; Olsson, Lennart

2004-10-01

The role of cranial neural crest cells in the formation of visceral arch musculature was investigated in the Mexican axolotl, Ambystoma mexicanum. DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine, perchlorate) labeling and green fluorescent protein (GFP) mRNA injections combined with unilateral transplantations of neural folds showed that neural crest cells contribute to the connective tissues but not the myofibers of developing visceral arch muscles in the mandibular, hyoid, and branchial arches. Extirpations of individual cranial neural crest streams demonstrated that neural crest cells are necessary for correct morphogenesis of visceral arch muscles. These do, however, initially develop in their proper positions also in the absence of cranial neural crest. Visceral arch muscles forming in the absence of neural crest cells start to differentiate at their origins but fail to extend toward their insertions and may have a frayed appearance. Our data indicate that visceral arch muscle positioning is controlled by factors that do not have a neural crest origin. We suggest that the cranial neural crest-derived connective tissues provide directional guidance important for the proper extension of the cranial muscles and the subsequent attachment to the insertion on the correct cartilage. In a comparative context, our data from the Mexican axolotl support the view that the cranial neural crest plays a fundamental role in the development of not only the skeleton of the vertebrate head but also in the morphogenesis of the cranial muscles and that this might be a primitive feature of cranial development in vertebrates. 2004 Wiley-Liss, Inc.

Extracellular matrix motion and early morphogenesis.

PubMed

Loganathan, Rajprasad; Rongish, Brenda J; Smith, Christopher M; Filla, Michael B; Czirok, Andras; Bénazéraf, Bertrand; Little, Charles D

2016-06-15

For over a century, embryologists who studied cellular motion in early amniotes generally assumed that morphogenetic movement reflected migration relative to a static extracellular matrix (ECM) scaffold. However, as we discuss in this Review, recent investigations reveal that the ECM is also moving during morphogenesis. Time-lapse studies show how convective tissue displacement patterns, as visualized by ECM markers, contribute to morphogenesis and organogenesis. Computational image analysis distinguishes between cell-autonomous (active) displacements and convection caused by large-scale (composite) tissue movements. Modern quantification of large-scale 'total' cellular motion and the accompanying ECM motion in the embryo demonstrates that a dynamic ECM is required for generation of the emergent motion patterns that drive amniote morphogenesis. © 2016. Published by The Company of Biologists Ltd.

Vertebral and femoral bone mineral density and bone strength in prostate cancer patients assessed in phantomless PET/CT examinations.

PubMed

Schwaiger, Benedikt J; Kopperdahl, David L; Nardo, Lorenzo; Facchetti, Luca; Gersing, Alexandra S; Neumann, Jan; Lee, Kwang J; Keaveny, Tony M; Link, Thomas M

2017-08-01

Bone fracture risk assessed ancillary to positron emission tomography with computed tomography co-registration (PET/CT) could provide substantial clinical value to oncology patients with elevated fracture risk without introducing additional radiation dose. The purpose of our study was to investigate the feasibility of obtaining valid measurements of bone mineral density (BMD) and finite element analysis-derived bone strength of the hip and spine using PET/CT examinations of prostate cancer patients by comparing against values obtained using routine multidetector-row computed tomography (MDCT) scans-as validated in previous studies-as a reference standard. Men with prostate cancer (n=82, 71.6±8.3 years) underwent Fluorine-18 NaF PET/CT and routine MDCT within three months. Femoral neck and total hip areal BMD, vertebral trabecular BMD and femur and vertebral strength based on finite element analysis were assessed in 63 paired PET/CT and MDCT examinations using phantomless calibration and Biomechanical-CT analysis. Men with osteoporosis or fragile bone strength identified at either the hip or spine (vertebral trabecular BMD ≤80mg/cm 3 , femoral neck or total hip T-score ≤-2.5, vertebral strength ≤6500N and femoral strength ≤3500N, respectively) were considered to be at high risk of fracture. PET/CT- versus MDCT-based BMD and strength measurements were compared using paired t-tests, linear regression and by generating Bland-Altman plots. Agreement in fracture-risk classification was assessed in a contingency table. All measurements from PET/CT versus MDCT were strongly correlated (R 2 =0.93-0.97; P<0.0001 for all). Mean differences for total hip areal BMD (0.001g/cm 2 , 1.1%), femoral strength (-60N, 1.3%), vertebral trabecular BMD (2mg/cm 3 , 2.6%) and vertebral strength (150N; 1.7%) measurements were not statistically significant (P>0.05 for all), whereas the mean difference in femoral neck areal BMD measurements was small but significant (-0.018g/cm 2 ; -2

Physical performance and radiographic and clinical vertebral fractures in older men.

PubMed

Cawthon, Peggy M; Blackwell, Terri L; Marshall, Lynn M; Fink, Howard A; Kado, Deborah M; Ensrud, Kristine E; Cauley, Jane A; Black, Dennis; Orwoll, Eric S; Cummings, Steven R; Schousboe, John T

2014-09-01

In men, the association between poor physical performance and likelihood of incident vertebral fractures is unknown. Using data from the MrOS study (N = 5958), we describe the association between baseline physical performance (walking speed, grip strength, leg power, repeat chair stands, narrow walk [dynamic balance]) and incidence of radiographic and clinical vertebral fractures. At baseline and follow-up an average of 4.6 years later, radiographic vertebral fractures were assessed using semiquantitative (SQ) scoring on lateral thoracic and lumbar radiographs. Logistic regression modeled the association between physical performance and incident radiographic vertebral fractures (change in SQ grade ≥1 from baseline to follow-up). Every 4 months after baseline, participants self-reported fractures; clinical vertebral fractures were confirmed by centralized radiologist review of the baseline study radiograph and community-acquired spine images. Proportional hazards regression modeled the association between physical performance with incident clinical vertebral fractures. Multivariate models were adjusted for age, bone mineral density (BMD, by dual-energy X-ray absorptiometry [DXA]), clinical center, race, smoking, height, weight, history of falls, activity level, and comorbid medical conditions; physical performance was analyzed as quartiles. Of 4332 men with baseline and repeat radiographs, 192 (4.4%) had an incident radiographic vertebral fracture. With the exception of walking speed, poorer performance on repeat chair stands, leg power, narrow walk, and grip strength were each associated in a graded manner with an increased risk of incident radiographic vertebral fracture (p for trend across quartiles <0.001). In addition, men with performance in the worst quartile on three or more exams had an increased risk of radiographic fracture (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.33-2.45) compared with men with better performance on all exams

Perithecium morphogenesis in Sordaria macrospora.

PubMed

Lord, Kathryn M; Read, Nick D

2011-04-01

The perithecium of the self-fertile ascomycete Sordaria macrospora provides an excellent model in which to analyse fungal multicellular development. This study provides a detailed analysis of perithecium morphogenesis in the wild type and eight developmental mutants of S. macrospora, using a range of correlative microscopical techniques. Fundamentally, perithecia and other complex multicellular structures produced by fungi arise by hyphal aggregation and adhesion, and these processes are followed by specialization and septation of hyphal compartments within the aggregates. Perithecial morphogenesis can be divided into the ascogonial, protoperithecial, and perithecial stages of development. At least 13 specialized, morphologically distinct cell-types are involved in perithecium morphogenesis, and these fall into three basic classes: hyphae, conglutinate cells and spores. Conglutinate cells arise from hyphal adhesion and certain perithecial hyphae develop from conglutinate cells. Various hypha-conglutinate cell transitions play important roles during the development of the perithecial wall and neck. Copyright © 2010. Published by Elsevier Inc.

Tooth-bone morphogenesis during postnatal stages of mouse first molar development

PubMed Central

Lungová, Vlasta; Radlanski, Ralf J; Tucker, Abigail S; Renz, Herbert; Míšek, Ivan; Matalová, Eva

2011-01-01

The first mouse molar (M1) is the most common model for odontogenesis, with research particularly focused on prenatal development. However, the functional dentition forms postnatally, when the histogenesis and morphogenesis of the tooth is completed, the roots form and the tooth physically anchors into the jaw. In this work, M1 was studied from birth to eruption, assessing morphogenesis, proliferation and apoptosis, and correlating these with remodeling of the surrounding bony tissue. The M1 completed crown formation between postnatal (P) days 0–2, and the development of the tooth root was initiated at P4. From P2 until P12, cell proliferation in the dental epithelium reduced and shifted downward to the apical region of the forming root. In contrast, proliferation was maintained or increased in the mesenchymal cells of the dental follicle. At later stages, before tooth eruption (P20), cell proliferation suddenly ceased. This withdrawal from the cell cycle correlated with tooth mineralization and mesenchymal differentiation. Apoptosis was observed during all stages of M1 postnatal morphogenesis, playing a role in the removal of cells such as osteoblasts in the mandibular region and working together with osteoclasts to remodel the bone around the developing tooth. At more advanced developmental stages, apoptotic cells and bodies accumulated in the cell layers above the tooth cusps, in the path of eruption. Three-dimensional reconstruction of the developing postnatal tooth and bone indicates that the alveolar crypts form by resorption underneath the primordia, whereas the ridges form by active bone growth between the teeth and roots to form a functional complex. PMID:21418206

Quantitative computed tomography-based predictions of vertebral strength in anterior bending.

PubMed

Buckley, Jenni M; Cheng, Liu; Loo, Kenneth; Slyfield, Craig; Xu, Zheng

2007-04-20

This study examined the ability of QCT-based structural assessment techniques to predict vertebral strength in anterior bending. The purpose of this study was to compare the abilities of QCT-based bone mineral density (BMD), mechanics of solids models (MOS), e.g., bending rigidity, and finite element analyses (FE) to predict the strength of isolated vertebral bodies under anterior bending boundary conditions. Although the relative performance of QCT-based structural measures is well established for uniform compression, the ability of these techniques to predict vertebral strength under nonuniform loading conditions has not yet been established. Thirty human thoracic vertebrae from 30 donors (T9-T10, 20 female, 10 male; 87 +/- 5 years of age) were QCT scanned and destructively tested in anterior bending using an industrial robot arm. The QCT scans were processed to generate specimen-specific FE models as well as trabecular bone mineral density (tBMD), integral bone mineral density (iBMD), and MOS measures, such as axial and bending rigidities. Vertebral strength in anterior bending was poorly to moderately predicted by QCT-based BMD and MOS measures (R2 = 0.14-0.22). QCT-based FE models were better strength predictors (R2 = 0.34-0.40); however, their predictive performance was not statistically different from MOS bending rigidity (P > 0.05). Our results suggest that the poor clinical performance of noninvasive structural measures may be due to their inability to predict vertebral strength under bending loads. While their performance was not statistically better than MOS bending rigidities, QCT-based FE models were moderate predictors of both compressive and bending loads at failure, suggesting that this technique has the potential for strength prediction under nonuniform loads. The current FE modeling strategy is insufficient, however, and significant modifications must be made to better mimic whole bone elastic and inelastic material behavior.

Developmental biology meets materials science: Morphogenesis of biomineralized structures.

PubMed

Wilt, Fred H

2005-04-01

Biomineralization is the process by which metazoa form hard minerals for support, defense, and feeding. The minerals so formed, e.g., teeth, bones, shells, carapaces, and spicules, are of considerable interest to chemists and materials scientists. The cell biology underlying biomineralization is not well understood. The study of the formation of mineralized structures in developing organisms offers opportunities for understanding some intriguing aspects of cell and developmental biology. Five examples of biomineralization are presented: (1) the formation of siliceous spicules and frustules in sponges and diatoms, respectively; (2) the structure of skeletal spicules composed of amorphous calcium carbonate in some tunicates; (3) the secretion of the prism and nacre of some molluscan shells; (4) the development of skeletal spicules of sea urchin embryos; and (5) the formation of enamel of vertebrate teeth. Some speculations on the cellular and molecular mechanisms that support biomineralization, and their evolutionary origins, are discussed.

Stripes and belly-spots – a review of pigment cell morphogenesis in vertebrates

PubMed Central

Kelsh, Robert N.; Harris, Melissa L.; Colanesi, Sarah; Erickson, Carol A.

2009-01-01

Pigment patterns in the integument have long-attracted attention from both scientists and non-scientists alike since their natural attractiveness combines with their excellence as models for the general problem of pattern formation. Pigment cells are formed from the neural crest and must migrate to reach their final locations. In this review, we focus on our current understanding of mechanisms underlying the control of pigment cell migration and patterning in diverse vertebrates. The model systems discussed here –chick, mouse, and zebrafish – each provide unique insights into the major morphogenetic events driving pigment pattern formation. In birds and mammals, melanoblasts must be specified before they can migrate on the dorsolateral pathway. Transmembrane receptors involved in guiding them onto this route include EphB2 and Ednrb2 in chick, and Kit in mouse. Terminal migration depends, in part, upon extracellular matrix reorganization by ADAMTS20. Invasion of the ectoderm, especially into the feather germ and hair follicles, requires specific signals that are beginning to be characterized. We summarize our current understanding of the mechanisms regulating melanoblast number and organization in the epidermis. We note the apparent differences in pigment pattern formation in poikilothermic vertebrates when compared with birds and mammals. With more pigment cell types, migration pathways are more complex and largely unexplored; nevertheless, a role for Kit signaling in melanophore migration is clear and indicates that at least some patterning mechanisms may be highly conserved. We summarize the multiple factors thought to contribute to zebrafish embryonic pigment pattern formation, highlighting a recent study identifying Sdf1a as one factor crucial for regulation of melanophore positioning. Finally, we discuss the mechanisms generating a second, metamorphic pigment pattern in adult fish, emphasizing recent studies strengthening the evidence that undifferentiated

The large Maf factor Traffic Jam controls gonad morphogenesis in Drosophila.

PubMed

Li, Michelle A; Alls, Jeffrey D; Avancini, Rita M; Koo, Karen; Godt, Dorothea

2003-11-01

Interactions between somatic and germline cells are critical for the normal development of egg and sperm. Here we show that the gene traffic jam (tj) produces a soma-specific factor that controls gonad morphogenesis and is required for female and male fertility. tj encodes the only large Maf factor in Drosophila melanogaster, an orthologue of the atypical basic Leu zipper transcription factors c-Maf and MafB/Kreisler in vertebrates. Expression of tj occurs in somatic gonadal cells that are in direct contact with germline cells throughout development. In tj mutant gonads, somatic cells fail to inter-mingle and properly envelop germline cells, causing an early block in germ cell differentiation. In addition, tj mutant somatic cells show an increase in the level of expression for several adhesion molecules. We propose that tj is a critical modulator of the adhesive properties of somatic cells, facilitating germline-soma interactions that are essential for germ cell differentiation.

The control of branching morphogenesis

PubMed Central

Iber, Dagmar; Menshykau, Denis

2013-01-01

Many organs of higher organisms are heavily branched structures and arise by an apparently similar process of branching morphogenesis. Yet the regulatory components and local interactions that have been identified differ greatly in these organs. It is an open question whether the regulatory processes work according to a common principle and how far physical and geometrical constraints determine the branching process. Here, we review the known regulatory factors and physical constraints in lung, kidney, pancreas, prostate, mammary gland and salivary gland branching morphogenesis, and describe the models that have been formulated to analyse their impacts. PMID:24004663

Enzymatic Metabolism of Vitamin A in Developing Vertebrate Embryos

PubMed Central

Metzler, Melissa A.; Sandell, Lisa L.

2016-01-01

Embryonic development is orchestrated by a small number of signaling pathways, one of which is the retinoic acid (RA) signaling pathway. Vitamin A is essential for vertebrate embryonic development because it is the molecular precursor of the essential signaling molecule RA. The level and distribution of RA signaling within a developing embryo must be tightly regulated; too much, or too little, or abnormal distribution, all disrupt embryonic development. Precise regulation of RA signaling during embryogenesis is achieved by proteins involved in vitamin A metabolism, retinoid transport, nuclear signaling, and RA catabolism. The reversible first step in conversion of the precursor vitamin A to the active retinoid RA is mediated by retinol dehydrogenase 10 (RDH10) and dehydrogenase/reductase (SDR family) member 3 (DHRS3), two related membrane-bound proteins that functionally activate each other to mediate the interconversion of retinol and retinal. Alcohol dehydrogenase (ADH) enzymes do not contribute to RA production under normal conditions during embryogenesis. Genes involved in vitamin A metabolism and RA catabolism are expressed in tissue-specific patterns and are subject to feedback regulation. Mutations in genes encoding these proteins disrupt morphogenesis of many systems in a developing embryo. Together these observations demonstrate the importance of vitamin A metabolism in regulating RA signaling during embryonic development in vertebrates. PMID:27983671

Influence of physical activity on vertebral strength during late adolescence.

PubMed

Junno, Juho-Antti; Paananen, Markus; Karppinen, Jaro; Tammelin, Tuija; Niinimäki, Jaakko; Lammentausta, Eveliina; Niskanen, Markku; Nieminen, Miika T; Järvelin, Marjo-Riitta; Takatalo, Jani; Tervonen, Osmo; Tuukkanen, Juha

2013-02-01

Reduced vertebral strength is a clear risk factor for vertebral fractures. Men and women with vertebral fractures often have reduced vertebral size and bone mineral density (BMD). Vertebral strength is controlled by both genetic and developmental factors. Malnutrition and low levels of physical activity are commonly considered to result in reduced bone size during growth. Several studies have also demonstrated the general relationship between BMD and physical activity in the appendicular skeleton. In this study, we wanted to clarify the role of physical activity on vertebral bodies. Vertebral dimensions appear to generally be less pliant than long bones when lifetime changes occur. We wanted to explore the association between physical activity during late adolescence and vertebral strength parameters such as cross-sectional size and BMD. The association between physical activity and vertebral strength was explored by measuring vertebral strength parameters and defining the level of physical activity during adolescence. The study population consisted of 6,928 males and females who, at 15 to 16 and 19 years of age, responded to a mailed questionnaire inquiring about their physical activity. A total of 558 individuals at the mean age of 21 years underwent magnetic resonance imaging (MRI) scans. We measured the dimensions of the fourth lumbar vertebra from the MRI scans of the Northern Finland Birth Cohort 1986 and performed T2* relaxation time mapping, reflective of BMD. Vertebral strength was based on these two parameters. We analyzed the association of physical activity on vertebral strength using the analysis of variance. We observed no association between the level of physical activity during late adolescence and vertebral strength at 21 years. Copyright © 2013 Elsevier Inc. All rights reserved.

bullwinkle and shark regulate dorsal-appendage morphogenesis in Drosophila oogenesis.

PubMed

Tran, David H; Berg, Celeste A

2003-12-01

bullwinkle (bwk) regulates embryonic anteroposterior patterning and, through a novel germline-to-soma signal, morphogenesis of the eggshell dorsal appendages. We screened for dominant modifiers of the bullwinkle mooseantler eggshell phenotype and identified shark, which encodes an SH2-domain, ankyrin-repeat tyrosine kinase. At the onset of dorsal-appendage formation, shark is expressed in a punctate pattern in the squamous stretch cells overlying the nurse cells. Confocal microscopy with cell-type-specific markers demonstrates that the stretch cells act as a substrate for the migrating dorsal-appendage-forming cells and extend cellular projections towards them. Mosaic analyses reveal that shark is required in follicle cells for cell migration and chorion deposition. Proper shark RNA expression in the stretch cells requires bwk activity, while restoration of shark expression in the stretch cells suppresses the bwk dorsal-appendage phenotype. These results suggest that shark plays an important downstream role in the bwk-signaling pathway. Candidate testing implicates Src42A in a similar role, suggesting conservation with a vertebrate signaling pathway involving non-receptor tyrosine kinases.

Roles for Msx and Dlx homeoproteins in vertebrate development.

PubMed

Bendall, A J; Abate-Shen, C

2000-04-18

This review provides a comparative analysis of the expression patterns, functions, and biochemical properties of Msx and Dlx homeobox genes. These comprise multi-gene families that are closely related with respect to sequence features as well as expression patterns during vertebrate development. Thus, members of the Msx and Dlx families are expressed in overlapping, but distinct, patterns and display complementary or antagonistic functions, depending upon the context. A common theme shared among Msx and Dlx genes is that they are required during early, middle, and late phases of development where their differential expression mediates patterning, morphogenesis, and histogenesis of tissues in which they are expressed. With respect to their biochemical properties, Msx proteins function as transcriptional repressors, while Dlx proteins are transcriptional activators. Moreover, their ability to oppose each other's transcriptional actions implies a mechanism underlying their complementary or antagonistic functions during development.

The cellular and molecular mechanisms of vertebrate lens development

PubMed Central

Cvekl, Aleš; Ashery-Padan, Ruth

2014-01-01

The ocular lens is a model system for understanding important aspects of embryonic development, such as cell specification and the spatiotemporally controlled formation of a three-dimensional structure. The lens, which is characterized by transparency, refraction and elasticity, is composed of a bulk mass of fiber cells attached to a sheet of lens epithelium. Although lens induction has been studied for over 100 years, recent findings have revealed a myriad of extracellular signaling pathways and gene regulatory networks, integrated and executed by the transcription factor Pax6, that are required for lens formation in vertebrates. This Review summarizes recent progress in the field, emphasizing the interplay between the diverse regulatory mechanisms employed to form lens progenitor and precursor cells and highlighting novel opportunities to fill gaps in our understanding of lens tissue morphogenesis. PMID:25406393

Discriminatory ability of quantitative ultrasound parameters and bone mineral density in a population-based sample of postmenopausal women with vertebral fractures: results of the Basel Osteoporosis Study.

PubMed

Hartl, F; Tyndall, A; Kraenzlin, M; Bachmeier, C; Gückel, C; Senn, U; Hans, D; Theiler, R

2002-02-01

The discriminatory potential to classify subjects with or without vertebral fractures was tested cross-sectionally with different methods for the measurement of bone status in a population-based sample of postmenopausal women. Quantitative ultrasound (QUS) measurement at the calcaneus (Lunar Achilles, Hologic Sahara), the proximal phalanges (Igea Bone Profiler), and measurement of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA; Lunar Expert) at several anatomic sites was performed in 500 postmenopausal women (aged 65-75 years) randomly selected from the population. In addition, 50 young female subjects (20-40 years old) had QUS measurements and served as controls to express QUS results as T-score values. Radiographs of the lumbar and thoracic spine were performed in the elderly women. Two independent radiologists reviewed the X-rays for the presence of vertebral fractures. Of 486 eligible study participants, no fracture was seen in 396 participants. Single vertebral fractures were observed in 71 subjects; 19 individuals presented multiple fractures. The overall prevalence of vertebral fractures was 18.5%. Participants without vertebral fractures were compared with subjects with vertebral fractures. Normal statistical distributions were found for all bone measurement results. Risk of vertebral fracture in subjects with no and multiple vertebral fracture was estimated using age adjusted odds ratios (ORs) for QUS and dual-energy X-ray absorptiometry (DXA) values. Each SD decrease in bone measurement increased the risk of multiple vertebral fracture by 3.0 (95% CI, 1.6-5.6) for the Achilles stiffness, by 3.8 (95% CI, 1.8-8.2) for the Sahara QUI, 2.1 (95% CI, 1.3-3.4) for the Bone Profiler amplitude-dependent speed of sound (AD-SOS), and 2.1 (95% CI, 1.2-3.9) and 2.4 (95% CI, 1.3-4.3) for DXA lumbar spine and for DXA total hip, respectively. Results of a discriminant analysis showed sensitivities between 84% and 58% and specificities between 72

Normal morphogenesis of epithelial tissues and progression of epithelial tumors

PubMed Central

Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

2011-01-01

Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

A global sensitivity analysis approach for morphogenesis models.

PubMed

Boas, Sonja E M; Navarro Jimenez, Maria I; Merks, Roeland M H; Blom, Joke G

2015-11-21

Morphogenesis is a developmental process in which cells organize into shapes and patterns. Complex, non-linear and multi-factorial models with images as output are commonly used to study morphogenesis. It is difficult to understand the relation between the uncertainty in the input and the output of such 'black-box' models, giving rise to the need for sensitivity analysis tools. In this paper, we introduce a workflow for a global sensitivity analysis approach to study the impact of single parameters and the interactions between them on the output of morphogenesis models. To demonstrate the workflow, we used a published, well-studied model of vascular morphogenesis. The parameters of this cellular Potts model (CPM) represent cell properties and behaviors that drive the mechanisms of angiogenic sprouting. The global sensitivity analysis correctly identified the dominant parameters in the model, consistent with previous studies. Additionally, the analysis provided information on the relative impact of single parameters and of interactions between them. This is very relevant because interactions of parameters impede the experimental verification of the predicted effect of single parameters. The parameter interactions, although of low impact, provided also new insights in the mechanisms of in silico sprouting. Finally, the analysis indicated that the model could be reduced by one parameter. We propose global sensitivity analysis as an alternative approach to study the mechanisms of morphogenesis. Comparison of the ranking of the impact of the model parameters to knowledge derived from experimental data and from manipulation experiments can help to falsify models and to find the operand mechanisms in morphogenesis. The workflow is applicable to all 'black-box' models, including high-throughput in vitro models in which output measures are affected by a set of experimental perturbations.

Sea Urchin Morphogenesis.

PubMed

McClay, David R

2016-01-01

In the sea urchin morphogenesis follows extensive molecular specification. The specification controls the many morphogenetic events and these, in turn, precede patterning steps that establish the larval body plan. To understand how the embryo is built it was necessary to understand those series of molecular steps. Here an example of the historical sequence of those discoveries is presented as it unfolded over the last 50 years, the years during which major progress in understanding development of many animals and plants was documented by CTDB. In sea urchin development a rich series of experimental studies first established many of the phenomenological components of skeletal morphogenesis and patterning without knowledge of the molecular components. The many discoveries of transcription factors, signals, and structural proteins that contribute to the shape of the endoskeleton of the sea urchin larva then followed as molecular tools became available. A number of transcription factors and signals were discovered that were necessary for specification, morphogenesis, and patterning. Perturbation of the transcription factors and signals provided the means for assembling models of the gene regulatory networks used for specification and controlled the subsequent morphogenetic events. The earlier experimental information informed perturbation experiments that asked how patterning worked. As a consequence it was learned that ectoderm provides a series of patterning signals to the skeletogenic cells and as a consequence the skeletogenic cells secrete a highly patterned skeleton based on their ability to genotypically decode the localized reception of several signals. We still do not understand the complexity of the signals received by the skeletogenic cells, nor do we understand in detail how the genotypic information shapes the secreted skeletal biomineral, but the current knowledge at least outlines the sequence of events and provides a useful template for future

Thyroid Dysfunction in an Adult Female Population: A population-based study of Latin American Vertebral Osteoporosis Study (LAVOS) - Puerto Rico Site Hypothyroidism in LAVOS-Puerto Rico site

PubMed Central

González-Rodríguez, Loida A.; Felici-Giovanini, Marcos E; Haddock, Lillian

2013-01-01

Objective To determine the prevalence of hypothyroidism in an adult female population in Puerto Rico and to determine the relationship between hypothyroidism, bone mineral density and vertebral and non-vertebral fractures in this population. Methods Data from the 400 subjects database of the Latin American Vertebral Osteoporosis Study (LAVOS), Puerto Rico site was reviewed. Patient’s medical history, anthropometric data, current medications, laboratories, and DXA results was extracted. Subjects with thyroid dysfunction were identified based on their previous medical history and levels of TSH. Bone Mineral Density was classified using the World Health Organization criteria. Crude prevalence of thyroid dysfunction were estimated with a confidence of 95% and weighted by the population distribution by age, according to the distribution by age group in the 2000 census. Bone mineral densities and prevalence of vertebral and non-vertebral fractures were compared among the groups. Results The weighted prevalence of hyperthyroidism in this population was 0.0043% (95% CI: −0.0021%, 0.0107%). The weighted prevalence of hypothyroidism was 24.2% (95% CI: 19.9%, 28.4%). Increased prevalence of hypothyroidism was found in participants 70 years or older. The mean BMD at spine, hip and femoral neck was similar among the groups. No difference in the proportion of participants with vertebral and non-vertebral fractures was found among the groups. Conclusion Our study found a high prevalence of hypothyroidism among adult postmenopausal females in Puerto Rico. No association between hypothyroidism and decreased bone mineral densities, vertebral or non-vertebral fractures was found in this population. PMID:23781620

Discordance between Prevalent Vertebral Fracture and Vertebral Strength Estimated by the Finite Element Method Based on Quantitative Computed Tomography in Patients with Type 2 Diabetes Mellitus

PubMed Central

2015-01-01

Background Bone fragility is increased in patients with type 2 diabetes mellitus (T2DM), but a useful method to estimate bone fragility in T2DM patients is lacking because bone mineral density alone is not sufficient to assess the risk of fracture. This study investigated the association between prevalent vertebral fractures (VFs) and the vertebral strength index estimated by the quantitative computed tomography-based nonlinear finite element method (QCT-based nonlinear FEM) using multi-detector computed tomography (MDCT) for clinical practice use. Research Design and Methods A cross-sectional observational study was conducted on 54 postmenopausal women and 92 men over 50 years of age, all of whom had T2DM. The vertebral strength index was compared in patients with and without VFs confirmed by spinal radiographs. A standard FEM procedure was performed with the application of known parameters for the bone material properties obtained from nondiabetic subjects. Results A total of 20 women (37.0%) and 39 men (42.4%) with VFs were identified. The vertebral strength index was significantly higher in the men than in the women (P<0.01). Multiple regression analysis demonstrated that the vertebral strength index was significantly and positively correlated with the spinal bone mineral density (BMD) and inversely associated with age in both genders. There were no significant differences in the parameters, including the vertebral strength index, between patients with and without VFs. Logistic regression analysis adjusted for age, spine BMD, BMI, HbA1c, and duration of T2DM did not indicate a significant relationship between the vertebral strength index and the presence of VFs. Conclusion The vertebral strength index calculated by QCT-based nonlinear FEM using material property parameters obtained from nondiabetic subjects, whose risk of fracture is lower than that of T2DM patients, was not significantly associated with bone fragility in patients with T2DM. This discordance

Confocal imaging of whole vertebrate embryos reveals novel insights into molecular and cellular mechanisms of organ development

NASA Astrophysics Data System (ADS)

Hadel, Diana M.; Keller, Bradley B.; Sandell, Lisa L.

2014-03-01

Confocal microscopy has been an invaluable tool for studying cellular or sub-cellular biological processes. The study of vertebrate embryology is based largely on examination of whole embryos and organs. The application of confocal microscopy to immunostained whole mount embryos, combined with three dimensional (3D) image reconstruction technologies, opens new avenues for synthesizing molecular, cellular and anatomical analysis of vertebrate development. Optical cropping of the region of interest enables visualization of structures that are morphologically complex or obscured, and solid surface rendering of fluorescent signal facilitates understanding of 3D structures. We have applied these technologies to whole mount immunostained mouse embryos to visualize developmental morphogenesis of the mammalian inner ear and heart. Using molecular markers of neuron development and transgenic reporters of neural crest cell lineage we have examined development of inner ear neurons that originate from the otic vesicle, along with the supporting glial cells that derive from the neural crest. The image analysis reveals a previously unrecognized coordinated spatial organization between migratory neural crest cells and neurons of the cochleovestibular nerve. The images also enable visualization of early cochlear spiral nerve morphogenesis relative to the developing cochlea, demonstrating a heretofore unknown association of neural crest cells with extending peripheral neurite projections. We performed similar analysis of embryonic hearts in mouse and chick, documenting the distribution of adhesion molecules during septation of the outflow tract and remodeling of aortic arches. Surface rendering of lumen space defines the morphology in a manner similar to resin injection casting and micro-CT.

[Correlation analysis of cement leakage with volume ratio of intravertebral bone cement to vertebral body and vertebral body wall incompetence in percutaneous vertebroplasty for osteoporotic vertebral compression fractures].

PubMed

Liang, De; Ye, Linqiang; Jiang, Xiaobing; Huang, Weiquan; Yao, Zhensong; Tang, Yongchao; Zhang, Shuncong; Jin, Daxiang

2014-11-01

To investigate the risk factors of cement leakage in percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF). Between March 2011 and March 2012, 98 patients with single level OVCF were treated by PVP, and the clinical data were analyzed retrospectively. There were 13 males and 85 females, with a mean age of 77.2 years (range, 54-95 years). The mean disease duration was 43 days (range, 15-120 days), and the mean T score of bone mineral density (BMD) was -3.8 (range, -6.7- -2.5). Bilateral transpedicular approach was used in all the patients. The patients were divided into cement leakage group and no cement leakage group by occurrence of cement leakage based on postoperative CT. Single factor analysis was used to analyze the difference between 2 groups in T score of BMD, operative level, preoperative anterior compression degree of operative vertebrae, preoperative middle compression degree of operative vertebrae, preoperative sagittal Cobb angle of operative vertebrae, preoperative vertebral body wall incompetence, cement volume, and volume ratio of intravertebral bone cement to vertebral body. All relevant factors were introduced to logistic regression analysis to analyze the risk factors of cement leakage. All procedures were performed successfully. The mean operation time was 40 minutes (range, 30-50 minutes), and the mean volume ratio of intravertebral bone cement to vertebral body was 24.88% (range, 7.84%-38.99%). Back pain was alleviated significantly in all the patients postoperatively. All patients were followed up with a mean time of 8 months (range, 6-12 months). Cement leakage occurred in 49 patients. Single factor analysis showed that there were significant differences in the volume ratio of intravertebral bone cement to vertebral body and preoperative vertebral body wall incompetence between 2 groups (P < 0.05), while no significant difference in T score of BMD, operative level, preoperative anterior compression degree of

Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis, Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins.

PubMed

Hyun, Seong-In; Weisberg, Andrea; Moss, Bernard

2017-08-01

The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino-acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Fluorescence microscopy experiments showed that I2 colocalized with a major membrane protein of immature and mature virions. We generated a cell line that constitutively expressed I2 and allowed construction of the VACV I2L deletion mutant vΔI2. As anticipated, vΔI2 was unable to replicate in cells that did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after immature virion formation, resulting in the accumulation of dense spherical particles instead of brick-shaped mature virions with well-defined core structures. The abnormal particles retained the D13 scaffold protein of immature virions, were severely deficient in the transmembrane proteins that comprise the entry fusion complex (EFC), and had increased amounts of unprocessed membrane and core proteins. Total lysates of cells infected with vΔI2 also had diminished EFC proteins due to instability attributed to their hydrophobicity and failure to be inserted into viral membranes. A similar instability of EFC proteins had previously been found with unrelated mutants blocked earlier in morphogenesis that also accumulated viral membranes retaining the D13 scaffold. We concluded that I2 is required for virion morphogenesis, release of the D13 scaffold, and the association of EFC proteins with viral membranes. IMPORTANCE Poxviruses comprise a large family that infect vertebrates and invertebrates, cause disease in both in humans and in wild and domesticated animals, and are being engineered as vectors for vaccines and cancer therapy. In addition, investigations of poxviruses have provided insights into

Deletion of the Vaccinia Virus I2 Protein Interrupts Virion Morphogenesis, Leading to Retention of the Scaffold Protein and Mislocalization of Membrane-Associated Entry Proteins

PubMed Central

Hyun, Seong-In; Weisberg, Andrea

2017-01-01

ABSTRACT The I2L open reading frame of vaccinia virus (VACV) encodes a conserved 72-amino-acid protein with a putative C-terminal transmembrane domain. Previous studies with a tetracycline-inducible mutant demonstrated that I2-deficient virions are defective in cell entry. The purpose of the present study was to determine the step of replication or entry that is affected by loss of the I2 protein. Fluorescence microscopy experiments showed that I2 colocalized with a major membrane protein of immature and mature virions. We generated a cell line that constitutively expressed I2 and allowed construction of the VACV I2L deletion mutant vΔI2. As anticipated, vΔI2 was unable to replicate in cells that did not express I2. Unexpectedly, morphogenesis was interrupted at a stage after immature virion formation, resulting in the accumulation of dense spherical particles instead of brick-shaped mature virions with well-defined core structures. The abnormal particles retained the D13 scaffold protein of immature virions, were severely deficient in the transmembrane proteins that comprise the entry fusion complex (EFC), and had increased amounts of unprocessed membrane and core proteins. Total lysates of cells infected with vΔI2 also had diminished EFC proteins due to instability attributed to their hydrophobicity and failure to be inserted into viral membranes. A similar instability of EFC proteins had previously been found with unrelated mutants blocked earlier in morphogenesis that also accumulated viral membranes retaining the D13 scaffold. We concluded that I2 is required for virion morphogenesis, release of the D13 scaffold, and the association of EFC proteins with viral membranes. IMPORTANCE Poxviruses comprise a large family that infect vertebrates and invertebrates, cause disease in both in humans and in wild and domesticated animals, and are being engineered as vectors for vaccines and cancer therapy. In addition, investigations of poxviruses have provided insights

Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2

PubMed Central

Nielson, Carrie M; Liu, Ching-Ti; Smith, Albert V; Ackert-Bicknell, Cheryl L; Reppe, Sjur; Jakobsdottir, Johanna; Wassel, Christina; Register, Thomas C; Oei, Ling; Alonso, Nerea; Oei, Edwin H; Parimi, Neeta; Samelson, Elizabeth J; Nalls, Mike A; Zmuda, Joseph; Lang, Thomas; Bouxsein, Mary; Latourelle, Jeanne; Claussnitzer, Melina; Siggeirsdottir, Kristin; Srikanth, Priya; Lorentzen, Erik; Vandenput, Liesbeth; Langefeld, Carl; Raffield, Laura; Terry, Greg; Cox, Amanda J; Allison, Matthew A; Criqui, Michael H; Bowden, Don; Ikram, M Arfan; Mellstrom, Dan; Karlsson, Magnus K; Carr, John; Budoff, Matthew; Phillips, Caroline; Cupples, L Adrienne; Chou, Wen-Chi; Myers, Richard H; Ralston, Stuart H; Gautvik, Kaare M; Cawthon, Peggy M; Cummings, Steven; Karasik, David; Rivadeneira, Fernando; Gudnason, Vilmundur; Orwoll, Eric S; Harris, Tamara B; Ohlsson, Claes; Kiel, Douglas P; Hsu, Yi-Hsiang

2017-01-01

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10−8) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p = 1.2 × 10−10) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10−4). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p = 1.7 × 10−3, functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to linkSLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help

Multicellular Models of Morphogenesis

EPA Science Inventory

EPA’s Virtual Embryo project (v-Embryo™), in collaboration with developers of CompuCell3D, aims to create computer models of morphogenesis that can be used to address the effects of chemical perturbation on embryo development at the cellular level. Such computational (in silico) ...

Inorganic, organic, and encapsulated minerals in vegetable meal based diets for Sparus aurata (Linnaeus, 1758)

PubMed Central

Rimoldi, Simona; Robaina, Lidia E.; Torrecillas, Silvia; Terova, Genciana; Zamorano, María J.; Karalazos, Vasileios; Hamre, Kristin; Izquierdo, Marisol

2017-01-01

Substituting fishmeal (FM) with vegetable meal (VM) can markedly affect the mineral composition of feeds, and may require additional mineral supplementation. Their bioavailability and optimal supplementation levels depend also on the form of delivery of minerals. The aim of the study was to determine the effect of different delivery forms of three major trace elements (Zn, Mn and Se) in a marine teleost. Gilthead sea bream juveniles of 22.5 g were fed a VM-based diet for 12 weeks that was either not supplemented with these minerals or supplemented with inorganic, organic, or encapsulated inorganic forms of minerals in triplicate and compared to a FM-based diet. Our results showed that mineral delivery form significantly affected the biochemical composition and morphology of posterior vertebrae. Supplementation of VM-based diets with inorganic forms of the target minerals significantly promoted growth, increased the vertebral weight and content of ash and Zn, enhanced bone mineralization and affected the vertebral shape. Conversely, encapsulation of inorganic minerals reduced fish growth and vertebral mineral content, whereas supplementation of organic minerals, enhanced bone osteogenesis by upregulating bone morphogenetic protein 2 (bmp2) gene and produced vertebrae with a larger length in relation to height. Furthermore, organic mineral forms of delivery downregulated the expression of oxidative stress related genes, such as Cu/Zn superoxide dismutase (Cu/Zn sod) and glutathione peroxidase 1 (gpx-1), suggesting thus that dietary minerals supplemented in the organic form could be reasonably considered more effective than the inorganic and encapsulated forms of supply. PMID:29093992

Programming Morphogenesis through Systems and Synthetic Biology.

PubMed

Velazquez, Jeremy J; Su, Emily; Cahan, Patrick; Ebrahimkhani, Mo R

2018-04-01

Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell-cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids. Copyright © 2017 Elsevier Ltd. All rights reserved.

Physics and the canalization of morphogenesis: a grand challenge in organismal biology

PubMed Central

von Dassow, Michelangelo; Davidson, Lance A.

2011-01-01

Morphogenesis takes place in a background of organism-to-organism and environmental variation. Therefore, a fundamental question in the study of morphogenesis is how the mechanical processes of tissue movement and deformation are affected by that variability, and in turn, how the mechanics of the system modulates phenotypic variation. We highlight a few key factors, including environmental temperature, embryo size, and environmental chemistry that might perturb the mechanics of morphogenesis in natural populations. Then we discuss several ways in which mechanics – including feedback from mechanical cues – might influence intra-specific variation in morphogenesis. To understand morphogenesis it will be necessary to consider whole-organism, environment, and evolutionary scales because these larger scales present the challenges that developmental mechanisms have evolved to cope with. Studying the variation organisms express and the variation organisms experience will aid in deciphering the causes of birth defects. PMID:21750364

Questioning hagfish affinities of the enigmatic Devonian vertebrate Palaeospondylus

NASA Astrophysics Data System (ADS)

Johanson, Zerina; Smith, Moya; Sanchez, Sophie; Senden, Tim; Trinajstic, Kate; Pfaff, Cathrin

2017-07-01

Palaeospondylus gunni Traquair, 1890 is an enigmatic Devonian vertebrate whose taxonomic affinities have been debated since it was first described. Most recently, Palaeospondylus has been identified as a stem-group hagfish (Myxinoidea). However, one character questioning this assignment is the presence of three semicircular canals in the otic region of the cartilaginous skull, a feature of jawed vertebrates. Additionally, new tomographic data reveal that the following characters of crown-group gnathostomes (chondrichthyans + osteichthyans) are present in Palaeospondylus: a longer telencephalic region of the braincase, separation of otic and occipital regions by the otico-occipital fissure, and vertebral centra. As well, a precerebral fontanelle and postorbital articulation of the palatoquadrate are characteristic of certain chondrichthyans. Similarities in the structure of the postorbital process to taxa such as Pucapampella, and possible presence of the ventral cranial fissure, both support a resolution of Pa. gunni as a stem chondrichthyan. The internally mineralized cartilaginous skeleton in Palaeospondylus may represent a stage in the loss of bone characteristic of the Chondrichthyes.

Enamel-like apatite crown covering amorphous mineral in a crayfish mandible

PubMed Central

Bentov, Shmuel; Zaslansky, Paul; Al-Sawalmih, Ali; Masic, Admir; Fratzl, Peter; Sagi, Amir; Berman, Amir; Aichmayer, Barbara

2012-01-01

Carbonated hydroxyapatite is the mineral found in vertebrate bones and teeth, whereas invertebrates utilize calcium carbonate in their mineralized organs. In particular, stable amorphous calcium carbonate is found in many crustaceans. Here we report on an unusual, crystalline enamel-like apatite layer found in the mandibles of the arthropod Cherax quadricarinatus (freshwater crayfish). Despite their very different thermodynamic stabilities, amorphous calcium carbonate, amorphous calcium phosphate, calcite and fluorapatite coexist in well-defined functional layers in close proximity within the mandible. The softer amorphous minerals are found primarily in the bulk of the mandible whereas apatite, the harder and less soluble mineral, forms a wear-resistant, enamel-like coating of the molar tooth. Our findings suggest a unique case of convergent evolution, where similar functional challenges of mastication led to independent developments of structurally and mechanically similar, apatite-based layers in the teeth of genetically remote phyla: vertebrates and crustaceans. PMID:22588301

Development and validation of a subject-specific finite element model of the functional spinal unit to predict vertebral strength.

PubMed

Lee, Chu-Hee; Landham, Priyan R; Eastell, Richard; Adams, Michael A; Dolan, Patricia; Yang, Lang

2017-09-01

Finite element models of an isolated vertebral body cannot accurately predict compressive strength of the spinal column because, in life, compressive load is variably distributed across the vertebral body and neural arch. The purpose of this study was to develop and validate a patient-specific finite element model of a functional spinal unit, and then use the model to predict vertebral strength from medical images. A total of 16 cadaveric functional spinal units were scanned and then tested mechanically in bending and compression to generate a vertebral wedge fracture. Before testing, an image processing and finite element analysis framework (SpineVox-Pro), developed previously in MATLAB using ANSYS APDL, was used to generate a subject-specific finite element model with eight-node hexahedral elements. Transversely isotropic linear-elastic material properties were assigned to vertebrae, and simple homogeneous linear-elastic properties were assigned to the intervertebral disc. Forward bending loading conditions were applied to simulate manual handling. Results showed that vertebral strengths measured by experiment were positively correlated with strengths predicted by the functional spinal unit finite element model with von Mises or Drucker-Prager failure criteria ( R 2  = 0.80-0.87), with areal bone mineral density measured by dual-energy X-ray absorptiometry ( R 2  = 0.54) and with volumetric bone mineral density from quantitative computed tomography ( R 2  = 0.79). Large-displacement non-linear analyses on all specimens did not improve predictions. We conclude that subject-specific finite element models of a functional spinal unit have potential to estimate the vertebral strength better than bone mineral density alone.

Intake of high levels of vitamin A and polyunsaturated fatty acids during different developmental periods modifies the expression of morphogenesis genes in European sea bass (Dicentrarchus labrax).

PubMed

Villeneuve, Laure A N; Gisbert, Enric; Moriceau, Jacques; Cahu, Chantal L; Zambonino Infante, José L

2006-04-01

The effect of the feeding period on larval development was investigated in European sea bass larvae by considering the expression level of some genes involved in morphogenesis. Larvae were fed a control diet except during three different periods (period A: from 8 to 13 d post-hatching (dph); period B: from 13 to 18 dph; period C: from 18 to 23 dph) with two compound diets containing high levels of vitamin A or PUFA. European sea bass morphogenesis was affected by these two dietary nutrients during the early stages of development. The genes involved in morphogenesis could be modulated between 8 and 13 dph, and our results indicated that retinoids and fatty acids influenced two different molecular pathways that in turn implicated two different gene cascades, resulting in two different kinds of malformation. Hypervitaminosis A delayed development, reducing the number of vertebral segments and disturbing bone formation in the cephalic region. These malformations were correlated to an upregulation of retinoic acid receptor gamma, retinoid X receptor (RXR) alpha and bone morphogenetic protein (BMP)4. An excess of PUFA accelerated the osteoblast differentiation process through the upregulation of RXRalpha and BMP4, leading to a supernumerary vertebra. These results suggest that the composition of diets devoted to marine fish larvae has a particularly determining effect before 13 dph on the subsequent development of larvae and juvenile fish.

A primary phosphorus-deficient skeletal phenotype in juvenile Atlantic salmon Salmo salar: the uncoupling of bone formation and mineralization.

PubMed

Witten, P E; Owen, M A G; Fontanillas, R; Soenens, M; McGurk, C; Obach, A

2016-02-01

To understand the effect of low dietary phosphorus (P) intake on the vertebral column of Atlantic salmon Salmo salar, a primary P deficiency was induced in post-smolts. The dietary P provision was reduced by 50% for a period of 10 weeks under controlled conditions. The animal's skeleton was subsequently analysed by radiology, histological examination, histochemical detection of minerals in bones and scales and chemical mineral analysis. This is the first account of how a primary P deficiency affects the skeleton in S. salar at the cellular and at the micro-anatomical level. Animals that received the P-deficient diet displayed known signs of P deficiency including reduced growth and soft, pliable opercula. Bone and scale mineral content decreased by c. 50%. On radiographs, vertebral bodies appear small, undersized and with enlarged intervertebral spaces. Contrary to the X-ray-based diagnosis, the histological examination revealed that vertebral bodies had a regular size and regular internal bone structures; intervertebral spaces were not enlarged. Bone matrix formation was continuous and uninterrupted, albeit without traces of mineralization. Likewise, scale growth continues with regular annuli formation, but new scale matrix remains without minerals. The 10 week long experiment generated a homogeneous osteomalacia of vertebral bodies without apparent induction of skeletal malformations. The experiment shows that bone formation and bone mineralization are, to a large degree, independent processes in the fish examined. Therefore, a deficit in mineralization must not be the only cause of the alterations of the vertebral bone structure observed in farmed S. salar. It is discussed how the observed uncoupling of bone formation and mineralization helps to better diagnose, understand and prevent P deficiency-related malformations in farmed S. salar. © 2015 The Authors.Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of The Fisheries Society of the

Extracellular matrix and growth factors in branching morphogenesis

NASA Technical Reports Server (NTRS)

Hardman, P.; Spooner, B. S.

1993-01-01

The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

Morphogenesis of the caenorhabditis elegans vulva.

PubMed

Schindler, Adam J; Sherwood, David R

2013-01-01

Understanding how cells move, change shape, and alter cellular behaviors to form organs, a process termed morphogenesis, is one of the great challenges of developmental biology. Formation of the Caenorhabditis elegans vulva is a powerful, simple, and experimentally accessible model for elucidating how morphogenetic processes produce an organ. In the first step of vulval development, three epithelial precursor cells divide and differentiate to generate 22 cells of 7 different vulval subtypes. The 22 vulval cells then rearrange from a linear array into a tube, with each of the seven cell types undergoing characteristic morphogenetic behaviors that construct the vulva. Vulval morphogenesis entails many of the same cellular activities that underlie organogenesis and tissue formation across species, including invagination, lumen formation, oriented cell divisions, cell–cell adhesion, cell migration, cell fusion, extracellular matrix remodeling, and cell invasion. Studies of vulval development have led to pioneering discoveries in a number of these processes and are beginning to bridge the gap between the pathways that specify cells and their connections to morphogenetic behaviors. The simplicity of the vulva and the experimental tools available in C. elegans will continue to make vulval morphogenesis a powerful paradigm to further our understanding of the largely mysterious mechanisms that build tissues and organs. © 2012 Wiley Periodicals, Inc.

Morphogenesis of the C. elegans vulva

PubMed Central

Schindler, Adam J

2012-01-01

Understanding how cells move, change shape, and alter cellular behaviors to form organs, a process termed morphogenesis, is one of the great challenges of developmental biology. Formation of the C. elegans vulva is a powerful, simple, and experimentally accessible model for elucidating how morphogenetic processes produce an organ. In the first step of vulval development, three epithelial precursor cells divide and differentiate to generate 22 cells of seven different vulval subtypes. The 22 vulval cells then rearrange from a linear array into a tube, with each of the seven cell types undergoing characteristic morphogenetic behaviours that construct the vulva. Vulval morphogenesis entails many of the same cellular activities that underlie organogenesis and tissue formation across species, including invagination, lumen formation, oriented cell divisions, cell-cell adhesion, cell migration, cell fusion, extracellular matrix remodelling and cell invasion. Studies of vulval development have led to pioneering discoveries in a number of these processes and are beginning to bridge the gap between the pathways that specify cells and their connections to morphogenetic behaviors. The simplicity of the vulva and the experimental tools available in C. elegans will continue to make vulval morphogenesis a powerful paradigm to further our understanding of the largely mysterious mechanisms that build tissues and organs. PMID:23418408

A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle.

PubMed

Spletter, Maria L; Barz, Christiane; Yeroslaviz, Assa; Zhang, Xu; Lemke, Sandra B; Bonnard, Adrien; Brunner, Erich; Cardone, Giovanni; Basler, Konrad; Habermann, Bianca H; Schnorrer, Frank

2018-05-30

Muscles organise pseudo-crystalline arrays of actin, myosin and titin filaments to build force-producing sarcomeres. To study sarcomerogenesis, we have generated a transcriptomics resource of developing Drosophila flight muscles and identified 40 distinct expression profile clusters. Strikingly, most sarcomeric components group in two clusters, which are strongly induced after all myofibrils have been assembled, indicating a transcriptional transition during myofibrillogenesis. Following myofibril assembly, many short sarcomeres are added to each myofibril. Subsequently, all sarcomeres mature, reaching 1.5 µm diameter and 3.2 µm length and acquiring stretch-sensitivity. The efficient induction of the transcriptional transition during myofibrillogenesis, including the transcriptional boost of sarcomeric components, requires in part the transcriptional regulator Spalt major. As a consequence of Spalt knock-down, sarcomere maturation is defective and fibers fail to gain stretch-sensitivity. Together, this defines an ordered sarcomere morphogenesis process under precise transcriptional control - a concept that may also apply to vertebrate muscle or heart development. © 2018, Spletter et al.

Built for speed: strain in the cartilaginous vertebral columns of sharks.

PubMed

Porter, M E; Diaz, Candido; Sturm, Joshua J; Grotmol, Sindre; Summers, A P; Long, John H

2014-02-01

In most bony fishes vertebral column strain during locomotion is almost exclusively in the intervertebral joints, and when these joints move there is the potential to store and release strain energy. Since cartilaginous fishes have poorly mineralized vertebral centra, we tested whether the vertebral bodies undergo substantial strain and thus may be sites of energy storage during locomotion. We measured axial strains of the intervertebral joints and vertebrae in vivo and ex vivo to characterize the dynamic behavior of the vertebral column. We used sonomicrometry to directly measure in vivo and in situ strains of intervertebral joints and vertebrae of Squalus acanthias swimming in a flume. For ex vivo measurements, we used a materials testing system to dynamically bend segments of vertebral column at frequencies ranging from 0.25 to 1.00 Hz and a range of physiologically relevant curvatures, which were determined using a kinematic analysis. The vertebral centra of S. acanthias undergo strain during in vivo volitional movements as well as in situ passive movements. Moreover, when isolated segments of vertebral column were tested during mechanical bending, we measured the same magnitudes of strain. These data support our hypothesis that vertebral column strain in lateral bending is not limited to the intervertebral joints. In histological sections, we found that the vertebral column of S. acanthias has an intracentral canal that is open and covered with a velum layer. An open intracentral canal may indicate that the centra are acting as tunics around some sections of a hydrostat, effectively stiffening the vertebral column. These data suggest that the entire vertebral column of sharks, both joints and centra, is mechanically engaged as a dynamic spring during locomotion. Copyright © 2013 Elsevier GmbH. All rights reserved.

Computational models of airway branching morphogenesis.

PubMed

Varner, Victor D; Nelson, Celeste M

2017-07-01

The bronchial network of the mammalian lung consists of millions of dichotomous branches arranged in a highly complex, space-filling tree. Recent computational models of branching morphogenesis in the lung have helped uncover the biological mechanisms that construct this ramified architecture. In this review, we focus on three different theoretical approaches - geometric modeling, reaction-diffusion modeling, and continuum mechanical modeling - and discuss how, taken together, these models have identified the geometric principles necessary to build an efficient bronchial network, as well as the patterning mechanisms that specify airway geometry in the developing embryo. We emphasize models that are integrated with biological experiments and suggest how recent progress in computational modeling has advanced our understanding of airway branching morphogenesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease.

PubMed

Heijckmann, Anna Caroline; Huijberts, Maya S P; Schoon, Erik J; Geusens, Piet; de Vries, Jolanda; Menheere, Paul P C A; van der Veer, Eveline; Wolffenbuttel, Bruce H R; Stockbrugger, Reinhold W; Dumitrescu, Bianca; Nieuwenhuijzen Kruseman, Arie C

2008-08-01

Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. One hundred and nine patients with Crohn's disease (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.

Origin of the vertebrate body plan via mechanically biased conservation of regular geometrical patterns in the structure of the blastula.

PubMed

Edelman, David B; McMenamin, Mark; Sheesley, Peter; Pivar, Stuart

2016-09-01

We present a plausible account of the origin of the archetypal vertebrate bauplan. We offer a theoretical reconstruction of the geometrically regular structure of the blastula resulting from the sequential subdivision of the egg, followed by mechanical deformations of the blastula in subsequent stages of gastrulation. We suggest that the formation of the vertebrate bauplan during development, as well as fixation of its variants over the course of evolution, have been constrained and guided by global mechanical biases. Arguably, the role of such biases in directing morphology-though all but neglected in previous accounts of both development and macroevolution-is critical to any substantive explanation for the origin of the archetypal vertebrate bauplan. We surmise that the blastula inherently preserves the underlying geometry of the cuboidal array of eight cells produced by the first three cleavages that ultimately define the medial-lateral, dorsal-ventral, and anterior-posterior axes of the future body plan. Through graphical depictions, we demonstrate the formation of principal structures of the vertebrate body via mechanical deformation of predictable geometrical patterns during gastrulation. The descriptive rigor of our model is supported through comparisons with previous characterizations of the embryonic and adult vertebrate bauplane. Though speculative, the model addresses the poignant absence in the literature of any plausible account of the origin of vertebrate morphology. A robust solution to the problem of morphogenesis-currently an elusive goal-will only emerge from consideration of both top-down (e.g., the mechanical constraints and geometric properties considered here) and bottom-up (e.g., molecular and mechano-chemical) influences. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A System for Modelling Cell–Cell Interactions during Plant Morphogenesis

PubMed Central

Dupuy, Lionel; Mackenzie, Jonathan; Rudge, Tim; Haseloff, Jim

2008-01-01

Background and aims During the development of multicellular organisms, cells are capable of interacting with each other through a range of biological and physical mechanisms. A description of these networks of cell–cell interactions is essential for an understanding of how cellular activity is co-ordinated in regionalized functional entities such as tissues or organs. The difficulty of experimenting on living tissues has been a major limitation to describing such systems, and computer modelling appears particularly helpful to characterize the behaviour of multicellular systems. The experimental difficulties inherent to the multitude of parallel interactions that underlie cellular morphogenesis have led to the need for computer models. Methods A new generic model of plant cellular morphogenesis is described that expresses interactions amongst cellular entities explicitly: the plant is described as a multi-scale structure, and interactions between distinct entities is established through a topological neighbourhood. Tissues are represented as 2D biphasic systems where the cell wall responds to turgor pressure through a viscous yielding of the cell wall. Key Results This principle was used in the development of the CellModeller software, a generic tool dedicated to the analysis and modelling of plant morphogenesis. The system was applied to three contrasting study cases illustrating genetic, hormonal and mechanical factors involved in plant morphogenesis. Conclusions Plant morphogenesis is fundamentally a cellular process and the CellModeller software, through its underlying generic model, provides an advanced research tool to analyse coupled physical and biological morphogenetic mechanisms. PMID:17921524

The case for applying tissue engineering methodologies to instruct human organoid morphogenesis.

PubMed

Marti-Figueroa, Carlos R; Ashton, Randolph S

2017-05-01

Three-dimensional organoids derived from human pluripotent stem cell (hPSC) derivatives have become widely used in vitro models for studying development and disease. Their ability to recapitulate facets of normal human development during in vitro morphogenesis produces tissue structures with unprecedented biomimicry. Current organoid derivation protocols primarily rely on spontaneous morphogenesis processes to occur within 3-D spherical cell aggregates with minimal to no exogenous control. This yields organoids containing microscale regions of biomimetic tissues, but at the macroscale (i.e. 100's of microns to millimeters), the organoids' morphology, cytoarchitecture, and cellular composition are non-biomimetic and variable. The current lack of control over in vitro organoid morphogenesis at the microscale induces aberrations at the macroscale, which impedes realization of the technology's potential to reproducibly form anatomically correct human tissue units that could serve as optimal human in vitro models and even transplants. Here, we review tissue engineering methodologies that could be used to develop powerful approaches for instructing multiscale, 3-D human organoid morphogenesis. Such technological mergers are critically needed to harness organoid morphogenesis as a tool for engineering functional human tissues with biomimetic anatomy and physiology. Human PSC-derived 3-D organoids are revolutionizing the biomedical sciences. They enable the study of development and disease within patient-specific genetic backgrounds and unprecedented biomimetic tissue microenvironments. However, their uncontrolled, spontaneous morphogenesis at the microscale yields inconsistences in macroscale organoid morphology, cytoarchitecture, and cellular composition that limits their standardization and application. Integration of tissue engineering methods with organoid derivation protocols could allow us to harness their potential by instructing standardized in vitro morphogenesis

Mechanical Control of Tissue Morphogenesis

PubMed Central

Patwari, Parth; Lee, Richard T.

2008-01-01

Mechanical forces participate in morphogenesis from the level of individual cells to whole organism patterning. This manuscript reviews recent research that has identified specific roles for mechanical forces in important developmental events. One well-defined example is that dynein-driven cilia create fluid flow that determines left-right patterning in the early mammalian embryo. Fluid flow is also important for vasculogenesis, and evidence suggests that fluid shear stress rather than fluid transport is primarily required for remodeling the early vasculature. Contraction of the actin cytoskeleton, driven by nonmuscle myosins and regulated by the Rho family GTPases, is a recurring mechanism for controlling morphogenesis throughout development, from gastrulation to cardiogenesis. Finally, novel experimental approaches suggest critical roles for the actin cytoskeleton and the mechanical environment in determining differentiation of mesenchymal stem cells. Insights into the mechanisms linking mechanical forces to cell and tissue differentiation pathways are important for understanding many congenital diseases and for developing regenerative medicine strategies. PMID:18669930

Severity of aortic calcification is positively associated with vertebral fracture in older men—a densitometry study in the STRAMBO cohort

PubMed Central

Samelson, E. J.; Sornay-Rendu, E.; Chapurlat, R.; Kiel, D. P.

2013-01-01

Summary In older men, severe abdominal aortic calcification and vertebral fracture (both assessed using dual-energy X-ray absorptiometry) were positively associated after adjustment for confounders including bone mineral density. Introduction Abdominal aortic calcification (AAC) is associated with higher fracture risk, independently of low bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) can be used to assess both vertebral fracture and AAC and requires less time, cost, and radiation exposure. Methods We conducted a cross-sectional study of the association between AAC and prevalent vertebral fractures in 901 men ≥50 years old. We used DXA (vertebral fracture assessment) to evaluate BMD, vertebral fracture, and AAC. Results Prevalence of vertebral fracture was 11 %. Median AAC score was 1 and 12 % of men had AAC score >6. After adjustment for age, weight, femoral neck BMD, smoking, ischemic heart disease, diabetes, and hypertension, AAC score >6 (vs ≤6) was associated with 2.5 (95 % CI, 1.4–4.5) higher odds of vertebral fracture. Odds of vertebral fracture for AAC score >6 increased with vertebral fracture severity (grade 1, OR=1.8; grade 2, OR=2.4; grade 3, OR=4.4; trend p<0.01) and with the number of vertebral fractures (1 fracture, OR=2.0, >1 fracture, OR=3.5). Prevalence of vertebral fracture was twice as high in men having both a T-score<−2.0 and an AAC score>6 compared with men having only one of these characteristics. Conclusions Men with greater severity AAC had greater severity and greater number of vertebral fractures, independently of BMD and co-morbidities. DXA can be used to assess vertebral fracture and AAC. It can provide a rapid, safe, and less expensive alternative to radiography. DXA may be an important clinical tool to identify men at high risk of adverse outcomes from osteoporosis and cardiovascular disease. PMID:22872071

Population-Wide Impact of Non-Hip Non-Vertebral Fractures on Mortality.

PubMed

Tran, Thach; Bliuc, Dana; van Geel, Tineke; Adachi, Jonathan D; Berger, Claudie; van den Bergh, Joop; Eisman, John A; Geusens, Piet; Goltzman, David; Hanley, David A; Josse, Robert G; Kaiser, Stephanie M; Kovacs, Christopher S; Langsetmo, Lisa; Prior, Jerilynn C; Nguyen, Tuan V; Center, Jacqueline R

2017-09-01

Data on long-term consequences of non-hip non-vertebral (NHNV) fractures, accounting for approximately two-thirds of all fragility fractures, are scanty. Our study aimed to quantify the population-wide impact of NHNV fractures on mortality. The national population-based prospective cohort study (Canadian Multicentre Osteoporosis Study) included 5526 community dwelling women and 2163 men aged 50 years or older followed from July 1995 to September 2013. Population impact number was used to quantify the average number of people for whom one death would be attributable to fracture and case impact number to quantify the number of deaths out of which one would be attributable to a fracture. There were 1370 fragility fractures followed by 296 deaths in women (mortality rate: 3.49; 95% CI, 3.11 to 3.91), and 302 fractures with 92 deaths in men (5.05; 95% CI, 4.12 to 6.20). NHNV fractures accounted for three-quarters of fractures. In women, the population-wide impact of NHNV fractures on mortality was greater than that of hip and vertebral fractures because of the greater number of NHNV fractures. Out of 800 women, one death was estimated to be attributable to a NHNV fracture, compared with one death in 2000 women attributable to hip or vertebral fracture. Similarly, out of 15 deaths in women, one was estimated to be attributable to a NHNV fracture, compared with one in over 40 deaths for hip or vertebral fracture. The impact of forearm fractures (ie, one death in 2400 women and one out of 42 deaths in women attributable to forearm fracture) was similar to that of hip, vertebral, or rib fractures. Similar, albeit not significant, results were noted for men. The study highlights the important contribution of NHNV fractures on mortality because many NHNV fracture types, except for the most distal fractures, have serious adverse consequences that affect a significant proportion of the population. © 2017 American Society for Bone and Mineral Research. © 2017 American Society

The Pea Seedling as a Model of Normal and Abnormal Morphogenesis

ERIC Educational Resources Information Center

Kurkdjian, Armen; And Others

1974-01-01

Describes several simple and inexpensive experiments designed to facilitate the study of normal and abnormal morphogenesis in the biology laboratory. Seedlings of the common garden pea are used in the experiments, and abnormal morphogenesis (tumors) are induced by a virulent strain of the crown-gall organism, Agrobacterium tumefaciens. (JR)

Mechanics and morphogenesis of fission yeast cells.

PubMed

Davì, Valeria; Minc, Nicolas

2015-12-01

The integration of biochemical and biomechanical elements is at the heart of morphogenesis. While animal cells are relatively soft objects which shape and mechanics is mostly regulated by cytoskeletal networks, walled cells including those of plants, fungi and bacteria are encased in a rigid cell wall which resist high internal turgor pressure. How these particular mechanical properties may influence basic cellular processes, such as growth, shape and division remains poorly understood. Recent work using the model fungal cell fission yeast, Schizosaccharomyces pombe, highlights important contribution of cell mechanics to various morphogenesis processes. We envision this genetically tractable system to serve as a novel standard for the mechanobiology of walled cell. Copyright © 2015 Elsevier Ltd. All rights reserved.

A right-handed signalling pathway drives heart looping in vertebrates

PubMed Central

Ocaña, Oscar H.; Coskun, Hakan; Minguillón, Carolina; Murawala, Prayag; Tanaka, Elly M.; Galcerán, Joan; Muñoz-Chapuli, Ramón; Nieto, M. Angela

2017-01-01

The majority of animals show external bilateral symmetry, precluding the observation of multiple internal left-right (L/R) asymmetries that are fundamental for organ packaging and function1,2. In vertebrates, left identity is mediated by the left-specific Nodal-Pitx2 axis that is repressed on the right-hand side by the epithelial-mesenchymal transition (EMT) inducer Snail13,4. Despite some existing evidence3,5, it remains unclear whether an equivalent instructive pathway provides right-hand specific information to the embryo. Here we show that in zebrafish, BMP mediates the L/R asymmetric activation of another EMT inducer, Prrx1a, in the lateral plate mesoderm (LPM) with higher levels on the right. Prrx1a drives L/R differential cell movements towards the midline leading to a leftward displacement of the cardiac posterior pole through an actomyosin-dependent mechanism. Downregulation of Prrx1a prevents heart looping and leads to mesocardia. Two parallel and mutually repressed pathways, respectively driven by Nodal and BMP on the left and right LPM, converge on the asymmetric activation of Pitx2 and Prrx1, two transcription factors that integrate left and right information to govern heart morphogenesis. This mechanism is conserved in the chicken embryo and, in the mouse, Snail1 fulfills the role played by Prrx1 in fish and chick. Thus, a differential L/R EMT produces asymmetric cell movements and forces, more prominent from the right, that drive heart laterality in vertebrates. PMID:28880281

Role of notochord cells and sclerotome-derived cells in vertebral column development in fugu, Takifugu rubripes: histological and gene expression analyses.

PubMed

Kaneko, Takamasa; Freeha, Khalid; Wu, Xiaoming; Mogi, Makoto; Uji, Susumu; Yokoi, Hayato; Suzuki, Tohru

2016-10-01

Despite the common structure of vertebrates, the development of the vertebral column differs widely between teleosts and tetrapods in several respects, including the ossification of the centrum and the function of the notochord. In contrast to tetrapods, vertebral development in teleosts is not fully understood, particularly for large fish with highly ossified bones. We therefore examined the histology and gene expression profile of vertebral development in fugu, Takifugu rubripes, a model organism for genomic research. Ossification of the fugu centrum is carried out by outer osteoblasts expressing col1a1, col2a1, and sparc, and the growing centra completely divide the notochord into double cone-shaped segments that function as intercentral joints. In this process, the notochord basal cells produce a thick notochord sheath exhibiting Alcian-blue-reactive cartilaginous properties and composing the intercentral ligament in cooperation with the external ligament connective tissue. Synthesis of the matrix by the basal cells was ascertained by an in vitro test. Expression of twist2 indicates that this connective tissue is descended from the embryonic sclerotome. Notochord basal cells express sox9, ihhb, shh, and col2a1a, suggesting that the signaling system involved in chondrocyte proliferation and matrix production also functions in notochord cells for notochord sheath formation. We further found that the notochord expression of both ntla and shh is maintained in the fugu vertebral column, whereas it is turned off after embryogenesis in zebrafish. Thus, our results demonstrate that, in contrast to zebrafish, a dynamic morphogenesis and molecular network continues to function in fugu until the establishment of the adult vertebral column.

Prevalence of silent vertebral fractures detected by vertebral fracture assessment in young Portuguese men with hyperthyroidism.

PubMed

Barbosa, Ana Paula; Rui Mascarenhas, Mário; Silva, Carlos Francisco; Távora, Isabel; Bicho, Manuel; do Carmo, Isabel; de Oliveira, António Gouveia

2015-02-01

Hyperthyroidism is a risk factor for reduced bone mineral density (BMD) and osteoporotic fractures. Vertebral fracture assessment (VFA) by dual-energy X-ray absorptiometry (DXA) is a radiological method of visualization of the spine, which enables patient comfort and reduced radiation exposure. This study was carried out to evaluate BMD and the prevalence of silent vertebral fractures in young men with hyperthyroidism. We conducted a cross-sectional study in a group of Portuguese men aged up to 50 years and matched in hyperthyroidism (n=24) and control (n=24) groups. A group of 48 Portuguese men aged up to 50 years was divided and matched in hyperthyroidism (n=24) and control (n=24) groups. BMD (g/cm(2)) at L1-L4, hip, radius 33%, and whole body as well as the total body masses (kg) were studied by DXA. VFA was used to detect fractures and those were classified by Genant's semiquantitative method. No patient had previously been treated for hyperthyroidism, osteoporosis, or low bone mass. Adequate statistical tests were used. The mean age, height, and total fat mass were similar in both groups (P≥0.05). The total lean body mass and the mean BMD at lumbar spine, hip, and whole body were significantly decreased in the hyperthyroidism group. In this group, there was also a trend for an increased prevalence of reduced BMD/osteoporosis and osteoporotic vertebral fractures. The results obtained using VFA technology (confirmed by X-ray) suggest that the BMD changes in young men with nontreated hyperthyroidism may lead to the development of osteoporosis and vertebral fractures. This supports the pertinence of using VFA in the routine of osteoporosis assessment to detect silent fractures precociously and consider early treatment. © 2015 European Society of Endocrinology.

Punctuated evolution and robustness in morphogenesis

PubMed Central

Grigoriev, D.; Reinitz, J.; Vakulenko, S.; Weber, A.

2014-01-01

This paper presents an analytic approach to the pattern stability and evolution problem in morphogenesis. The approach used here is based on the ideas from the gene and neural network theory. We assume that gene networks contain a number of small groups of genes (called hubs) controlling morphogenesis process. Hub genes represent an important element of gene network architecture and their existence is empirically confirmed. We show that hubs can stabilize morphogenetic pattern and accelerate the morphogenesis. The hub activity exhibits an abrupt change depending on the mutation frequency. When the mutation frequency is small, these hubs suppress all mutations and gene product concentrations do not change, thus, the pattern is stable. When the environmental pressure increases and the population needs new genotypes, the genetic drift and other effects increase the mutation frequency. For the frequencies that are larger than a critical amount the hubs turn off; and as a result, many mutations can affect phenotype. This effect can serve as an engine for evolution. We show that this engine is very effective: the evolution acceleration is an exponential function of gene redundancy. Finally, we show that the Eldredge-Gould concept of punctuated evolution results from the network architecture, which provides fast evolution, control of evolvability, and pattern robustness. To describe analytically the effect of exponential acceleration, we use mathematical methods developed recently for hard combinatorial problems, in particular, for so-called k-SAT problem, and numerical simulations. PMID:24996115

A segmental pattern of alkaline phosphatase activity within the notochord coincides with the initial formation of the vertebral bodies.

PubMed

Grotmol, Sindre; Nordvik, Kari; Kryvi, Harald; Totland, Geir K

2005-05-01

This study shows that segmental expression of alkaline phosphatase (ALP) activity by the notochord of the Atlantic salmon (Salmo salar L.) coincides with the initial mineralization of the vertebral body (chordacentrum), and precedes ALP expression by presumed somite-derived cells external to the notochordal sheath. The early expression of ALP indicates that the notochord plays an instructive role in the segmental patterning of the vertebral column. The chordacentra form segmentally as mineralized rings within the notochordal sheath, and ALP activity spreads within the chordoblast layer from ventral to dorsal, displaying the same progression and spatial distribution as the mineralization process. No ALP activity was observed in sclerotomal mesenchyme surrounding the notochordal sheath during initial formation of the chordacentra. Our results support previous findings indicating that the chordoblasts initiate a segmental differentiation of the notochordal sheath into chordacentra and intervertebral regions.

Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial.

PubMed

Katzman, W B; Vittinghoff, E; Kado, D M; Lane, N E; Ensrud, K E; Shipp, K

2016-03-01

Biomechanical analyses support the theory that thoracic spine hyperkyphosis may increase risk of new vertebral fractures. While greater kyphosis was associated with an increased rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture. Biomechanical analyses suggest hyperkyphosis may increase risk of incident vertebral fracture by increasing the load on vertebral bodies during daily activities. We propose to assess the association of kyphosis with incident radiographic vertebral fracture. We used data from the Fracture Intervention Trial among 3038 women 55-81 years of age with low bone mineral density (BMD). Baseline kyphosis angle was measured using a Debrunner kyphometer. Vertebral fractures were assessed at baseline and follow-up from lateral radiographs of the thoracic and lumbar spine. We used Poisson models to estimate the independent association of kyphosis with incident fracture, controlling for age and femoral neck BMD. Mean baseline kyphosis was 48° (SD = 12) (range 7-83). At baseline, 962 (32%) participants had a prevalent fracture. There were 221 incident fractures over a median of 4 years. At baseline, prevalent fracture was associated with 3.7° greater average kyphosis (95% CI 2.8-4.6, p < 0.0005), adjusting for age and femoral neck BMD. Before adjusting for prevalent fracture, each 10° greater kyphosis was associated with 22% increase (95% CI 8-38%, p = 0.001) in annualized rate of new radiographic vertebral fracture, adjusting for age and femoral neck BMD. After additional adjustment for prevalent fracture, estimated increased annualized rate was attenuated and no longer significant, 8% per 10° kyphosis (95% CI -4 to 22%, p = 0.18). While greater kyphosis increased the rate of incident vertebral fractures, our analysis does not

Thoracic kyphosis and rate of incident vertebral fractures: the Fracture Intervention Trial

PubMed Central

Vittinghoff, E.; Kado, D. M.; Lane, N. E.; Ensrud, K. E.; Shipp, K.

2016-01-01

Summary Biomechanical analyses support the theory that thoracic spine hyperkyphosis may increase risk of new vertebral fractures. While greater kyphosis was associated with an increased rate of incident vertebral fractures, our analysis does not show an independent association of kyphosis on incident fracture, after adjustment for prevalent vertebral fracture. Excessive kyphosis may still be a clinical marker for prevalent vertebral fracture. Introduction Biomechanical analyses suggest hyperkyphosis may increase risk of incident vertebral fracture by increasing the load on vertebral bodies during daily activities. We propose to assess the association of kyphosis with incident radiographic vertebral fracture. Methods We used data from the Fracture Intervention Trial among 3038 women 55–81 years of age with low bone mineral density (BMD). Baseline kyphosis angle was measured using a Debrunner kyphometer. Vertebral fractures were assessed at baseline and follow-up from lateral radiographs of the thoracic and lumbar spine. We used Poisson models to estimate the independent association of kyphosis with incident fracture, controlling for age and femoral neck BMD. Results Mean baseline kyphosis was 48° (SD = 12) (range 7–83). At baseline, 962 (32 %) participants had a prevalent fracture. There were 221 incident fractures over a median of 4 years. At baseline, prevalent fracture was associated with 3.7° greater average kyphosis (95 % CI 2.8–4.6, p < 0.0005), adjusting for age and femoral neck BMD. Before adjusting for prevalent fracture, each 10° greater kyphosis was associated with 22 % increase (95 % CI 8–38 %, p = 0.001) in annualized rate of new radiographic vertebral fracture, adjusting for age and femoral neck BMD. After additional adjustment for prevalent fracture, estimated increased annualized rate was attenuated and no longer significant, 8 % per 10° kyphosis (95 % CI −4 to 22 %, p = 0.18). Conclusions While greater kyphosis increased the rate of

Cell confinement controls centrosome positioning and lumen initiation during epithelial morphogenesis

PubMed Central

Rodríguez-Fraticelli, Alejo E.; Auzan, Muriel; Alonso, Miguel A.; Bornens, Michel

2012-01-01

Epithelial organ morphogenesis involves sequential acquisition of apicobasal polarity by epithelial cells and development of a functional lumen. In vivo, cells perceive signals from components of the extracellular matrix (ECM), such as laminin and collagens, as well as sense physical conditions, such as matrix stiffness and cell confinement. Alteration of the mechanical properties of the ECM has been shown to promote cell migration and invasion in cancer cells, but the effects on epithelial morphogenesis have not been characterized. We analyzed the effects of cell confinement on lumen morphogenesis using a novel, micropatterned, three-dimensional (3D) Madin-Darby canine kidney cell culture method. We show that cell confinement, by controlling cell spreading, limits peripheral actin contractility and promotes centrosome positioning and lumen initiation after the first cell division. In addition, peripheral actin contractility is mediated by master kinase Par-4/LKB1 via the RhoA–Rho kinase–myosin II pathway, and inhibition of this pathway restores lumen initiation in minimally confined cells. We conclude that cell confinement controls nuclear–centrosomal orientation and lumen initiation during 3D epithelial morphogenesis. PMID:22965908

Developmental evolutionary biology of the vertebrate ear: conserving mechanoelectric transduction and developmental pathways in diverging morphologies

NASA Technical Reports Server (NTRS)

Fritzsch, B.; Beisel, K. W.; Bermingham, N. A.

2000-01-01

This brief overview shows that a start has been made to molecularly dissect vertebrate ear development and its evolutionary conservation to the development of the insect hearing organ. However, neither the patterning process of the ear nor the patterning process of insect sensory organs is sufficiently known at the moment to provide more than a first glimpse. Moreover, hardly anything is known about otocyst development of the cephalopod molluscs, another triploblast lineage that evolved complex 'ears'. We hope that the apparent conserved functional and cellular components present in the ciliated sensory neurons/hair cells will also be found in the genes required for vertebrate ear and insect sensory organ morphogenesis (Fig. 3). Likewise, we expect that homologous pre-patterning genes will soon be identified for the non-sensory cell development, which is more than a blocking of neuronal development through the Delta/Notch signaling system. Generation of the apparently unique ear could thus represent a multiplication of non-sensory cells by asymmetric and symmetric divisions as well as modification of existing patterning process by implementing novel developmental modules. In the final analysis, the vertebrate ear may come about by increasing the level of gene interactions in an already existing and highly conserved interactive cascade of bHLH genes. Since this was apparently achieved in all three lineages of triploblasts independently (Fig. 3), we now need to understand how much of the morphogenetic cascades are equally conserved across phyla to generate complex ears. The existing mutations in humans and mice may be able to point the direction of future research to understand the development of specific cell types and morphologies in the formation of complex arthropod, cephalopod, and vertebrate 'ears'.

Un(MaSC)ing Stem Cell Dynamics in Mammary Branching Morphogenesis.

PubMed

Greenwood, Erin; Wrenn, Emma D; Cheung, Kevin J

2017-02-27

The properties of stem cells that participate in mammary gland branching morphogenesis remain contested. Reporting in Nature, Scheele et al. (2017) establish a model for post-pubertal mammary branching morphogenesis in which position-dependent, lineage-restricted stem cells undergo cell mixing in order to contribute to long-term growth. Copyright © 2017 Elsevier Inc. All rights reserved.

Adenosine kinase modulates root gravitropism and cap morphogenesis in Arabidopsis.

PubMed

Young, Li-Sen; Harrison, Benjamin R; Narayana Murthy, U M; Moffatt, Barbara A; Gilroy, Simon; Masson, Patrick H

2006-10-01

Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular levels of adenosine, thereby modulating methyltransferase reactions, production of polyamines and secondary compounds, and cell signaling in animals. Unfortunately, little is known about ADK's contribution to the regulation of plant growth and development. Here, we show that ADK is a modulator of root cap morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and activity increase in the root tip. Mutation in one of two Arabidopsis (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects, along with alterations in root sensitivity to gravistimulation and slower kinetics of root gravitropic curvature. The kinetics defect can be partially rescued by adding spermine to the growth medium, whereas the defects in cap morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3 auxin efflux facilitator in the cap and decreased expression of the auxin-responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot develop a lateral auxin gradient across the cap, necessary for the curvature response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic alkalinization of the root statocytes, suggesting either that ADK1 functions between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or that the pH and PIN3-relocalization responses to gravistimulation belong to distinct branches of the pathway. Our data are consistent with a role for ADK and the S-adenosyl-L-methionine pathway in the control of root gravitropism and cap morphogenesis.

Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis

PubMed Central

Hielscher, Abigail; Ellis, Kim; Qiu, Connie; Porterfield, Josh; Gerecht, Sharon

2016-01-01

The extracellular matrix (ECM) has been demonstrated to facilitate angiogenesis. In particular, fibronectin has been documented to activate endothelial cells, resulting in their transition from a quiescent state to an active state in which the cells exhibit enhanced migration and proliferation. The goal of this study is to examine the role of polymerized fibronectin during vascular tubulogenesis using a 3 dimensional (3D) cell-derived de-cellularized matrix. A fibronectin-rich 3D de-cellularized ECM was used as a scaffold to study vascular morphogenesis of endothelial cells (ECs). Confocal analyses of several matrix proteins reveal high intra- and extra-cellular deposition of fibronectin in formed vascular structures. Using a small peptide inhibitor of fibronectin polymerization, we demonstrate that inhibition of fibronectin fibrillogenesis in ECs cultured atop de-cellularized ECM resulted in decreased vascular morphogenesis. Further, immunofluorescence and ultrastructural analyses reveal decreased expression of stromal matrix proteins in the absence of polymerized fibronectin with high co-localization of matrix proteins found in association with polymerized fibronectin. Evaluating vascular kinetics, live cell imaging showed that migration, migration velocity, and mean square displacement, are disrupted in structures grown in the absence of polymerized fibronectin. Additionally, vascular organization failed to occur in the absence of a polymerized fibronectin matrix. Consistent with these observations, we tested vascular morphogenesis following the disruption of EC adhesion to polymerized fibronectin, demonstrating that block of integrins α5β1 and αvβ3, abrogated vascular morphogenesis. Overall, fibronectin deposition in a 3D cell-derived de-cellularized ECM appears to be imperative for matrix assembly and vascular morphogenesis. PMID:26811931

Feedback, Lineages and Self-Organizing Morphogenesis

PubMed Central

Calof, Anne L.; Lowengrub, John S.; Lander, Arthur D.

2016-01-01

Feedback regulation of cell lineage progression plays an important role in tissue size homeostasis, but whether such feedback also plays an important role in tissue morphogenesis has yet to be explored. Here we use mathematical modeling to show that a particular feedback architecture in which both positive and negative diffusible signals act on stem and/or progenitor cells leads to the appearance of bistable or bi-modal growth behaviors, ultrasensitivity to external growth cues, local growth-driven budding, self-sustaining elongation, and the triggering of self-organization in the form of lamellar fingers. Such behaviors arise not through regulation of cell cycle speeds, but through the control of stem or progenitor self-renewal. Even though the spatial patterns that arise in this setting are the result of interactions between diffusible factors with antagonistic effects, morphogenesis is not the consequence of Turing-type instabilities. PMID:26989903

Notochord segmentation may lay down the pathway for the development of the vertebral bodies in the Atlantic salmon.

PubMed

Grotmol, Sindre; Kryvi, Harald; Nordvik, Kari; Totland, Geir K

2003-12-01

This study indicates that the development of the vertebrae in the Atlantic salmon requires the orchestration of two sources of metameric patterning, derived from the notochord and the somite rows, respectively. Before segmentation of the salmon notochord, chordoblasts exhibit a well-defined cell axis that is uniformly aligned with the cranio-caudal axis. The morphology of these cells is characterised by a foot-like basal projection that rests on the notochordal sheath. Notochordal segments are initially formed within the chordoblast layer by metameric change in the axial orientation of groups of chordoblasts. This process results in the formation of circular bands of chordoblasts, with feet perpendicular to the cranio-caudal axis, the original chordoblast orientation. Each vertebra is defined by two such chordoblast bands, at the cranial and caudal borders, respectively. Formation of the chordoblast segments closely precedes formation of the chordacentra, which form as calcified rings within the adjacent notochordal sheath. Sclerotomal osteoblasts then differentiate on the surface of the chordacentra, using them as foundations for further vertebral growth. Thus, the morphogenesis of the rudiments of the vertebral bodies is initiated by a generation of segments within the chordoblast layer. This dual segmentation model for salmon, in which the segmental patterns of the neural and haemal arches are somite-derived, while the vertebral segments seem to be notochord-derived, contrasts with current models for avians and mammals.

Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

PubMed Central

McNulty, Shannon; Bornmann, William; Schriewer, Jill; Werner, Chas; Smith, Scott K.; Olson, Victoria A.; Damon, Inger K.; Buller, R. Mark; Heuser, John; Kalman, Daniel

2010-01-01

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses. PMID:20526370

The role of bone shape in determining gender differences in vertebral bone mass.

PubMed

Barlow, Tricia; Carlino, Will; Blades, Heather Z; Crook, Jon; Harrison, Rachel; Arundel, Paul; Bishop, Nick J

2011-01-01

Dual-energy X-ray absorptiometry (DXA) measures of bone mineral density (BMD) in children fail to account for growth because bone depth is unmeasured. While multiple adjustment methods have been proposed using body or bone size, the effect of vertebral shape is relatively unknown. Our study aimed to determine gender differences in vertebral shape and their impact on areal BMD (aBMD). We recruited 189 children, including 107 boys, aged 4-17 years, who attended the emergency department due to trauma. None had fractured. Height, weight, Tanner stage, and DXA measurements of the lumbar spine (LS) and total body were obtained. Cylindrical models were used to predict relationships between vertebral width (VW) and areal density for a given vertebral area assuming uniform volumetric density. The actual relationships between VW, bone area, and aBMD for the LS in the children were then determined. The theoretical models predicted a positive relationship between width and areal density for a constant vertebral area. Actual vertebral measurements demonstrated that boys had greater VW for a given vertebral area but lower aBMD for a given VW than girls at any age. The most likely explanation for the apparent paradox was that vertebral cortical thickness relative to width was greater in girls. This difference remained after adjusting for lean mass, suggesting that bone's response to mechanical stimulation may vary between the sexes during growth with consequent evolutionary advantage for girls approaching reproductive age. Copyright © 2011 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Carlactone-independent seedling morphogenesis in Arabidopsis.

PubMed

Scaffidi, Adrian; Waters, Mark T; Ghisalberti, Emilio L; Dixon, Kingsley W; Flematti, Gavin R; Smith, Steven M

2013-10-01

Strigolactone hormones are derived from carotenoids via carlactone, and act through the α/β-hydrolase D14 and the F-box protein D3/MAX2 to repress plant shoot branching. While MAX2 is also necessary for normal seedling development, D14 and the known strigolactone biosynthesis genes are not, raising the question of whether endogenous, canonical strigolactones derived from carlactone have a role in seedling morphogenesis. Here, we report the chemical synthesis of the strigolactone precursor carlactone, and show that it represses Arabidopsis shoot branching and influences leaf morphogenesis via a mechanism that is dependent on the cytochrome P450 MAX1. In contrast, both physiologically active Z-carlactone and the non-physiological E isomer exhibit similar weak activity in seedlings, and predominantly signal through D14 rather than its paralogue KAI2, in a MAX2-dependent but MAX1-independent manner. KAI2 is essential for seedling morphogenesis, and hence this early-stage development employs carlactone-independent morphogens for which karrikins from wildfire smoke are specific surrogates. While the commonly employed synthetic strigolactone GR24 acts non-specifically through both D14 and KAI2, carlactone is a specific effector of strigolactone signalling that acts through MAX1 and D14. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Multi-scale mechanics from molecules to morphogenesis

PubMed Central

Davidson, Lance; von Dassow, Michelangelo; Zhou, Jian

2009-01-01

Dynamic mechanical processes shape the embryo and organs during development. Little is understood about the basic physics of these processes, what forces are generated, or how tissues resist or guide those forces during morphogenesis. This review offers an outline of some of the basic principles of biomechanics, provides working examples of biomechanical analyses of developing embryos, and reviews the role of structural proteins in establishing and maintaining the mechanical properties of embryonic tissues. Drawing on examples we highlight the importance of investigating mechanics at multiple scales from milliseconds to hours and from individual molecules to whole embryos. Lastly, we pose a series of questions that will need to be addressed if we are to understand the larger integration of molecular and physical mechanical processes during morphogenesis and organogenesis. PMID:19394436

Morphogenesis in bat wings: linking development, evolution and ecology.

PubMed

Adams, Rick A

2008-01-01

The evolution of powered flight in mammals required specific developmental shifts from an ancestral limb morphology to one adapted for flight. Through studies of comparative morphogenesis, investigators have quantified points and rates of divergence providing important insights into how wings evolved in mammals. Herein I compare growth,development and skeletogenesis of forelimbs between bats and the more ancestral state provided by the rat (Rattus norvegicus)and quantify growth trajectories that illustrate morphological divergence both developmentally and evolutionarily. In addition, I discuss how wing shape is controlled during morphogenesis by applying multivariate analyses of wing bones and wing membranes and discuss how flight dynamics are stabilized during flight ontogeny. Further, I discuss the development of flight in bats in relation to the ontogenetic niche and how juveniles effect populational foraging patterns. In addition, I provide a hypothetical ontogenetic landscape model that predicts how and when selection is most intense during juvenile morphogenesis and test this model with data from a population of the little brown bat, Myotis lucifugus. (c) 2007 S. Karger AG, Basel

Sex hormones, sex hormone binding globulin, and vertebral fractures in older men.

PubMed

Cawthon, Peggy M; Schousboe, John T; Harrison, Stephanie L; Ensrud, Kristine E; Black, Dennis; Cauley, Jane A; Cummings, Steven R; LeBlanc, Erin S; Laughlin, Gail A; Nielson, Carrie M; Broughton, Augusta; Kado, Deborah M; Hoffman, Andrew R; Jamal, Sophie A; Barrett-Connor, Elizabeth; Orwoll, Eric S

2016-03-01

The association between sex hormones and sex hormone binding globin (SHBG) with vertebral fractures in men is not well studied. In these analyses, we determined whether sex hormones and SHBG were associated with greater likelihood of vertebral fractures in a prospective cohort study of community dwelling older men. We included data from participants in MrOS who had been randomly selected for hormone measurement (N=1463, including 1054 with follow-up data 4.6years later). Major outcomes included prevalent vertebral fracture (semi-quantitative grade≥2, N=140, 9.6%) and new or worsening vertebral fracture (change in SQ grade≥1, N=55, 5.2%). Odds ratios per SD decrease in sex hormones and per SD increase in SHBG were estimated with logistic regression adjusted for potentially confounding factors, including age, bone mineral density, and other sex hormones. Higher SHBG was associated with a greater likelihood of prevalent vertebral fractures (OR: 1.38 per SD increase, 95% CI: 1.11, 1.72). Total estradiol analyzed as a continuous variable was not associated with prevalent vertebral fractures (OR per SD decrease: 0.86, 95% CI: 0.68 to 1.10). Men with total estradiol values ≤17pg/ml had a borderline higher likelihood of prevalent fracture than men with higher values (OR: 1.46, 95% CI: 0.99, 2.16). There was no association between total testosterone and prevalent fracture. In longitudinal analyses, SHBG (OR: 1.42 per SD increase, 95% CI: 1.03, 1.95) was associated with new or worsening vertebral fracture, but there was no association with total estradiol or total testosterone. In conclusion, higher SHBG (but not testosterone or estradiol) is an independent risk factor for vertebral fractures in older men. Copyright © 2016 Elsevier Inc. All rights reserved.

Sulphated glycosaminoglycans and proteoglycans in the developing vertebral column of juvenile Atlantic salmon (Salmo salar).

PubMed

Hannesson, Kirsten O; Ytteborg, Elisabeth; Takle, Harald; Enersen, Grethe; Bæverfjord, Grete; Pedersen, Mona E

2015-08-01

In the present study, the distribution of sulphated glycosaminoglycans (GAGs) in the developing vertebral column of Atlantic salmon (Salmo salar) at 700, 900, 1100 and 1400 d° was examined by light microscopy. The mineralization pattern was outlined by Alizarin red S and soft structures by Alcian blue. The temporal and spatial distribution patterns of different types of GAGs: chondroitin-4-sulphate/dermatan sulphate, chondroitin-6-sulphate, chondroitin-0-sulphate and keratan sulphate were addressed by immunohistochemistry using monoclonal antibodies against the different GAGs. The specific pattern obtained with the different antibodies suggests a unique role of the different GAG types in pattern formation and mineralization. In addition, the distribution of the different GAG types in normal and malformed vertebral columns from 15 g salmon was compared. A changed expression pattern of GAGs was found in the malformed vertebrae, indicating the involvement of these molecules during the pathogenesis. The molecular size of proteoglycans (PGs) in the vertebrae carrying GAGs was analysed with western blotting, and mRNA transcription of the PGs aggrecan, decorin, biglycan, fibromodulin and lumican by real-time qPCR. Our study reveals the importance of GAGs in development of vertebral column also in Atlantic salmon and indicates that a more comprehensive approach is necessary to completely understand the processes involved.

Spatial mapping and quantification of developmental branching morphogenesis.

PubMed

Short, Kieran; Hodson, Mark; Smyth, Ian

2013-01-15

Branching morphogenesis is a fundamental developmental mechanism that shapes the formation of many organs. The complex three-dimensional shapes derived by this process reflect equally complex genetic interactions between branching epithelia and their surrounding mesenchyme. Despite the importance of this process to normal adult organ function, analysis of branching has been stymied by the absence of a bespoke method to quantify accurately the complex spatial datasets that describe it. As a consequence, although many developmentally important genes are proposed to influence branching morphogenesis, we have no way of objectively assessing their individual contributions to this process. We report the development of a method for accurately quantifying many aspects of branching morphogenesis and we demonstrate its application to the study of organ development. As proof of principle we have employed this approach to analyse the developing mouse lung and kidney, describing the spatial characteristics of the branching ureteric bud and pulmonary epithelia. To demonstrate further its capacity to profile unrecognised genetic contributions to organ development, we examine Tgfb2 mutant kidneys, identifying elements of both developmental delay and specific spatial dysmorphology caused by haplo-insufficiency for this gene. This technical advance provides a crucial resource that will enable rigorous characterisation of the genetic and environmental factors that regulate this essential and evolutionarily conserved developmental mechanism.

DEVELOPMENTAL PALEOBIOLOGY OF THE VERTEBRATE SKELETON.

PubMed

Rücklin, Martin; Donoghue, Philip C J; Cunningham, John A; Marone, Federica; Stampanoni, Marco

2014-07-01

Studies of the development of organisms can reveal crucial information on homology of structures. Developmental data are not peculiar to living organisms, and they are routinely preserved in the mineralized tissues that comprise the vertebrate skeleton, allowing us to obtain direct insight into the developmental evolution of this most formative of vertebrate innovations. The pattern of developmental processes is recorded in fossils as successive stages inferred from the gross morphology of multiple specimens and, more reliably and routinely, through the ontogenetic stages of development seen in the skeletal histology of individuals. Traditional techniques are destructive and restricted to a 2-D plane with the third dimension inferred. Effective non-invasive methods of visualizing paleohistology to reconstruct developmental stages of the skeleton are necessary. In a brief survey of paleohistological techniques we discuss the pros and cons of these methods. The use of tomographic methods to reconstruct development of organs is exemplified by the study of the placoderm dentition. Testing evidence for the presence of teeth in placoderms, the first jawed vertebrates, we compare the methods that have been used. These include inferring the development from morphology, and using serial sectioning, microCT or synchrotron X-ray tomographic microscopy (SRXTM) to reconstruct growth stages and directions of growth. The ensuing developmental interpretations are biased by the methods and degree of inference. The most direct and reliable method is using SRXTM data to trace sclerochronology. The resulting developmental data can be used to resolve homology and test hypotheses on the origin of evolutionary novelties.

Increased vertebral bone mineral in response to reduced exercise in amenorrheic runners.

PubMed

Lindberg, J S; Powell, M R; Hunt, M M; Ducey, D E; Wade, C E

1987-01-01

Seven female runners found to have exercise-induced amenorrhea and decreased bone mineral were reevaluated after 15 months. During the 15-month period, four runners took supplemental calcium and reduced their weekly running distance by 43%, resulting in an average 5% increase in body weight, increased estradiol levels and eumenorrhea. Bone mineral content increased from 1.003+/-0.097 to 1.070+/-0.089 grams per cm.(2) Three runners continued to have amenorrhea, with no change in running distance or body weight. Estradiol levels remained abnormally low and there was no significant change in the bone mineral content, although all three took supplemental calcium. We found that early osteopenia associated with exercise-induced menstrual dysfunction improved when runners reduced their running distance, gained weight and became eumenorrheic.

Increased Vertebral Bone Mineral in Response to Reduced Exercise in Amenorrheic Runners

PubMed Central

Lindberg, Jill S.; Hunt, Marjorie M.; Wade, Charles E.; Powell, Malcolm R.; Ducey, Diane E.

1987-01-01

Seven female runners found to have exercise-induced amenorrhea and decreased bone mineral were reevaluated after 15 months. During the 15-month period, four runners took supplemental calcium and reduced their weekly running distance by 43%, resulting in an average 5% increase in body weight, increased estradiol levels and eumenorrhea. Bone mineral content increased from 1.003±0.097 to 1.070±0.089 grams per cm.2 Three runners continued to have amenorrhea, with no change in running distance or body weight. Estradiol levels remained abnormally low and there was no significant change in the bone mineral content, although all three took supplemental calcium. We found that early osteopenia associated with exercise-induced menstrual dysfunction improved when runners reduced their running distance, gained weight and became eumenorrheic. ImagesFigure 1. PMID:3825107

The influence of fat infiltration of back extensor muscles on osteoporotic vertebral fractures.

PubMed

So, Kwang-Young; Kim, Dae-Hee; Choi, Dong-Hyuk; Kim, Choong-Young; Kim, Jeong-Seok; Choi, Yong-Soo

2013-12-01

Retrospective study. To investigate the influence of fat infiltration at low back extensor muscles on osteoporotic vertebral fracture. In persons with stronger back muscles, the risk of osteoporotic vertebral fractures will likely be lower than in those persons with weaker back muscles. However, the degree of influence of fat infiltration of the back extensor muscle on osteoporotic vertebral fracture remains controversial. Two hundred and thirty-seven patients who had undergone lumbar spine magnetic resonance imaging and bone mineral density (BMD) were enrolled in this study. The amount of low back extensor muscle was determined using the pseudocoloring technique on an axial view of the L3 level. The patients were divided into two groups: osteoporotic vertebral fracture group (group A) and non-fracture group (group B). The amount of low back extensor muscle is compared with BMD, degenerative change of disc, osteophyte grade of facet joint and promontory angle to reveal the association between these factors. A negative correlation is found between age and the amount of low back extensor muscle (p=0.001). The amount of low back extensor muscle in group A and group B was 60.3%±14.5% and 64.2%±9.3% respectively, thus showing a significantly smaller amount of low back extensor muscle in the osteoporotic vertebral fracture group (p=0.015). Fat infiltration of low back extensor muscle was increased in osteoporotic vertebral fracture patients. Therefore, fat infiltration of low back extensor muscle in an elderly person may be a risk factor of osteoporotic vertebral fracture.

AmphiFoxE4, an amphioxus winged helix/forkhead gene encoding a protein closely related to vertebrate thyroid transcription factor-2: expression during pharyngeal development

NASA Technical Reports Server (NTRS)

Yu, Jr-Kai; Holland, Linda Z.; Jamrich, Milan; Blitz, Ira L.; Hollan, Nicholas D.

2002-01-01

The full-length sequence and developmental expression of amphioxus AmphiFoxE4 are described. Transcripts of the gene are first detected in the pharyngeal endoderm, where the club-shaped gland is forming and subsequently in the definitive gland itself. AmphiFoxE4 is closely related to vertebrate genes encoding the thyroid-specific transcription factor-2 (TTF2), which plays an early developmental role in the morphogenesis of the thyroid gland and a later role in hormone-mediated control of thyroid function. In amphioxus, AmphiFoxE4 expression is not thyroid specific because the club-shaped gland, the only structure expressing the gene, is not homologous to the vertebrate thyroid; instead, the thyroid homologue of amphioxus is a specialized region of the pharyngeal endoderm called the endostyle. We propose that (a) the pharynx of an amphioxus-like ancestor of the vertebrates included a club-shaped gland that expressed FoxE4 as well as an endostyle that did not, and (b) the club-shaped gland soon disappeared in the vertebrate line of descent but (c) not before there was a homeogenetic transfer of FoxE4 expression from the club-shaped gland to the nearby endostyle. Such a transfer could have provided part of the genetic program enabling the endostyle to separate from the pharyngeal endoderm and migrate away as the rudiment of the thyroid gland.

Cilia in vertebrate left–right patterning

PubMed Central

Dasgupta, Agnik

2016-01-01

Understanding how left–right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left–right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic ‘left–right organizer’. These flows direct asymmetric activation of a conserved Nodal (TGFβ) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left–right organizer, both of which are critical for effective cilia function during left–right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left–right organizer. This suggests the possibility that these cells acquire left–right positional information prior to the appearance of cilia. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821522

Cilia in vertebrate left-right patterning.

PubMed

Dasgupta, Agnik; Amack, Jeffrey D

2016-12-19

Understanding how left-right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left-right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic 'left-right organizer'. These flows direct asymmetric activation of a conserved Nodal (TGFβ) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left-right organizer, both of which are critical for effective cilia function during left-right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left-right organizer. This suggests the possibility that these cells acquire left-right positional information prior to the appearance of cilia.This article is part of the themed issue 'Provocative questions in left-right asymmetry'. © 2016 The Author(s).

The Ron Receptor Tyrosine Kinase Negatively Regulates Mammary Gland Branching Morphogenesis

PubMed Central

Meyer, Sara E.; Zinser, Glendon M.; Stuart, William D.; Pathrose, Peterson; Waltz, Susan E.

2009-01-01

The Ron receptor tyrosine kinase is expressed in normal breast tissue and is overexpressed in approximately 50% of human breast cancers. Despite the recent studies on Ron in breast cancer, nothing is known about the importance of this protein during breast development. To investigate the functional significance of Ron in the normal mammary gland, we compared mammary gland development in wild-type mice to mice containing a targeted ablation of the tyrosine kinase (TK) signaling domain of Ron (TK−/−). Mammary glands from RonTK−/− mice exhibited accelerated pubertal development including significantly increased ductal extension and branching morphogenesis. While circulating levels of estrogen, progesterone, and overall rates of epithelial cell turnover were unchanged, significant increases in phosphorylated MAPK, which predominantly localized to the epithelium, were associated with increased branching morphogenesis. Additionally, purified RonTK−/− epithelial cells cultured ex vivo exhibited enhanced branching morphogenesis, which was reduced upon MAPK inhibition. Microarray analysis of pubertal RonTK−/− glands revealed 393 genes temporally impacted by Ron expression with significant changes observed in signaling networks regulating development, morphogenesis, differentiation, cell motility, and adhesion. In total, these studies represent the first evidence of a role for the Ron receptor tyrosine kinase as a critical negative regulator of mammary development. PMID:19576199

Relationship Between BMD and Prevalent Vertebral Fractures in Indian Women Older Than 50 Yr.

PubMed

Gupta, Yashdeep; Marwaha, Raman K; Kukreja, Subhash; Bhadra, Kuntal; Narang, Archana; Mani, Kalaivani; Mithal, Ambrish; Tandon, Nikhil

2016-01-01

The purpose of the study was to study the relationship of morphometric vertebral fractures with bone mineral density (BMD) in Indian women older than 50 yr. Four hundred fifteen healthy Indian women older than 50 yr (mean age: 62.8 yr) underwent lateral X-rays of the lumbar and thoracic spine. Genant's semiquantitative method was used to diagnose and classify morphometric vertebral fractures. BMD was measured by DXA at lumbar spine and total hip. Recruited subjects underwent anthropometric, biochemical, and hormonal evaluation. Vertebral fractures were present in 17.1% (95% confidence interval: 13.5, 20.8) subjects. Prevalence of osteoporosis based on BMD was 35.7%. By adding those with prevalent fractures, the number of women requiring therapy for osteoporosis would increase to 46.5%. The BMD measured at femur neck, total hip, and lumbar spine (L1eL4) was not found to be lower in women with vertebral fractures as compared with those without fractures. BMD was not found to be lower in women with vertebral fractures as compared with those without fractures. Significant number of additional subjects with BMD in the normal or osteopenic range become eligible for osteoporosis treatment when presence of vertebral fracture is used as an independent indication for such treatment. Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Expression and Functional Role of Sprouty-2 in Breast Morphogenesis

PubMed Central

Hilmarsdottir, Bylgja; Gustafsdottir, Sigrun M.; Franzdottir, Sigridur Rut; Arason, Ari Jon; Steingrimsson, Eirikur; Magnusson, Magnus K.; Gudjonsson, Thorarinn

2013-01-01

Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR) and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2) in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D) culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD) resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an important regulator of

Expression and functional role of sprouty-2 in breast morphogenesis.

PubMed

Sigurdsson, Valgardur; Ingthorsson, Saevar; Hilmarsdottir, Bylgja; Gustafsdottir, Sigrun M; Franzdottir, Sigridur Rut; Arason, Ari Jon; Steingrimsson, Eirikur; Magnusson, Magnus K; Gudjonsson, Thorarinn

2013-01-01

Branching morphogenesis is a mechanism used by many species for organogenesis and tissue maintenance. Receptor tyrosine kinases (RTKs), including epidermal growth factor receptor (EGFR) and the sprouty protein family are believed to be critical regulators of branching morphogenesis. The aim of this study was to analyze the expression of Sprouty-2 (SPRY2) in the mammary gland and study its role in branching morphogenesis. Human breast epithelial cells, breast tissue and mouse mammary glands were used for expression studies using immunoblotting, real rime PCR and immunohistochemistry. Knockdown of SPRY2 in the breast epithelial stem cell line D492 was done by lentiviral transduction of shRNA constructs targeting SPRY2. Three dimensional culture of D492 with or without endothelial cells was done in reconstituted basement membrane matrix. We show that in the human breast, SPRY2 is predominantly expressed in the luminal epithelial cells of both ducts and lobuli. In the mouse mammary gland, SPRY2 expression is low or absent in the virgin state, while in the pregnant mammary gland SPRY2 is expressed at branching epithelial buds with increased expression during lactation. This expression pattern is closely associated with the activation of the EGFR pathway. Using D492 which generates branching structures in three-dimensional (3D) culture, we show that SPRY2 expression is low during initiation of branching with subsequent increase throughout the branching process. Immunostaining locates expression of phosphorylated SPRY2 and EGFR at the tip of lobular-like, branching ends. SPRY2 knockdown (KD) resulted in increased migration, increased pERK and larger and more complex branching structures indicating a loss of negative feedback control during branching morphogenesis. In D492 co-cultures with endothelial cells, D492 SPRY2 KD generates spindle-like colonies that bear hallmarks of epithelial to mesenchymal transition. These data indicate that SPRY2 is an important regulator of

Vertebral pneumatocysts.

PubMed

Arslan, G; Ceken, K; Cubuk, M; Ozkaynak, C; Lüleci, E

2001-01-01

To review the prevalence and location of vertebral pneumatocysts and evaluate the CT findings of these benign lesions. Retrospectively we reviewed CT images of 89 patients with suspected disc disease during a 6-month period. Distinctive CT pattern of intraosseous pneumatocysts involving the cervical, thoracic and lumbar spine was found. In 8 patients (9%), 10 vertebral pneumatocysts were detected. Five were located in the vertebral body and 4 of these were associated with vacuum phenomenon in adjacent intervertebral discs. Five were located near the facet joint and all were associated with vacuum phenomenon in adjacent facet joint. Intraosseous pneumatocyst is a benign lesion, therefore biopsy and follow-up are unnecessary. Although vertebral pneumatocysts seem to be uncommon with a few reported cases, this study shows them to be more frequent than previously thought.

Human Development VI: Supracellular Morphogenesis. The Origin of Biological and Cellular Order

PubMed Central

Ventegodt, Søren; Hermansen, Tyge Dahl; Flensborg-Madsen, Trine; Nielsen, Maj Lyck; Merrick, Joav

2006-01-01

Uninterrupted morphogenesis shows the informational potentials of biological organisms. Experimentally disturbed morphogenesis shows the compensational dynamics of the biological informational system, which is the rich informational redundancy. In this paper, we use these data to describe morphogenesis in terms of the development of supracellular levels of the organism, and we define complex epigenesis and supracellular differentiation. We review the phenomena of regeneration and induction of Hydra and amphibians, and the higher animals informational needs for developing their complex nervous systems. We argue, also building on the NO-GO theorem for ontogenesis as chemistry, that the traditional chemical explanations of high-level informational events in ontogenesis, such as transmutation, regeneration, and induction, are insufficient. We analyze the informational dynamics of three embryonic compensatory reactions to different types of disturbances: (1) transmutations of the imaginal discs of insects, (2) regeneration after removal of embryonic tissue, and (3) embryonic induction, where two tissues that normally are separated experimentally are made to influence each other. We describe morphogenesis as a complex bifurcation, and the resulting morphological levels of the organism as organized in a fractal manner and supported by positional information. We suggest that some kind of real nonchemical phenomenon must be taking form in living organisms as an information-carrying dynamic fractal field, causing morhogenesis and supporting the organisms morphology through time. We argue that only such a phenomenon that provides information-directed self-organization to the organism is able to explain the observed dynamic distribution of biological information through morphogenesis and the organism's ability to rejuvenate and heal. PMID:17115082

High Incidence of Vertebral Fractures in Children with Acute Lymphoblastic Leukemia 12 Months After the Initiation of Therapy

PubMed Central

Alos, Nathalie; Grant, Ronald; Ramsay, Timothy; Halton, Jacqueline; Cummings, Elizabeth A.; Miettunen, Paivi M.; Abish, Sharon; Atkinson, Stephanie; Barr, Ronald; Cabral, David A.; Cairney, Elizabeth; Couch, Robert; Dix, David B.; Fernandez, Conrad V.; Hay, John; Israels, Sara; Laverdière, Caroline; Lentle, Brian; Lewis, Victor; Matzinger, MaryAnn; Rodd, Celia; Shenouda, Nazih; Stein, Robert; Stephure, David; Taback, Shayne; Wilson, Beverly; Williams, Kathryn; Rauch, Frank; Siminoski, Kerry; Ward, Leanne M.

2014-01-01

Purpose Vertebral fractures due to osteoporosis are a potential complication of childhood acute lymphoblastic leukemia (ALL). To date, the incidence of vertebral fractures during ALL treatment has not been reported. Patient and Methods We prospectively evaluated 155 children with ALL during the first 12 months of leukemia therapy. Lateral thoracolumbar spine radiographs were obtained at baseline and 12 months. Vertebral bodies were assessed for incident vertebral fractures using the Genant semi-quantitative method, and relevant clinical indices such as spine bone mineral density (BMD), back pain and the presence of vertebral fractures at baseline were analyzed for association with incident vertebral fractures. Results Of the 155 children, 25 (16%, 95% Confidence Interval (CI) 11% to 23%) had a total of 61 incident vertebral fractures, of which 32 (52%) were moderate or severe. Thirteen of the 25 children with incident vertebral fractures (52%) also had fractures at baseline. Vertebral fractures at baseline increased the odds of an incident fracture at 12 months by an odds ratio of 7.3 (95% CI 2.3 to 23.1, p = 0.001). In addition, for every one standard deviation reduction in spine BMD Z-score at baseline, there was 1.8-fold increased odds of incident vertebral fracture at 12 months (95% CI 1.2 to 2.7, p = 0.006). Conclusion Children with ALL have a high incidence of vertebral fractures after 12 months of chemotherapy, and the presence of vertebral fractures and reductions in spine BMD Z-scores at baseline are highly associated clinical features. PMID:22734031

Prevalence of vertebral fracture in Asian men and women: comparison between Hong Kong, Thailand, Indonesia and Japan.

PubMed

Kwok, A W L; Leung, J C S; Chan, A Y H; Au, B S K; Lau, E M C; Yurianto, H; Yuktanandana, P; Yoshimura, N; Muraki, S; Oka, H; Akune, T; Leung, P C

2012-06-01

Little is known about the prevalence of vertebral fracture among Asians. This study investigated the prevalence of radiographically defined vertebral fracture, and identified associated risk factors in the aged population of four Asian countries. In total, 1588 males and females aged ≥ 65 years were recruited from Hong Kong, Thailand, Indonesia and Japan. Standard X-rays for the spine were taken and vertebral heights were measured. Vertebral fracture was defined as a reduction of >3 standard deviations in vertebral height ratio. Bone mineral density (BMD) of the hip was measured by dual energy X-ray absorptiometry, and anthropometric measurements were taken in Hong Kong and Japan. Other relevant data were entered in a standard questionnaire. The prevalence of vertebral fracture for both males and females was highest in Japan for younger (65-74 years) and older (≥ 75 years) age groups (36.6% and 37.6% for males; 18.8% and 28.7% for females). Lower hip BMD was associated with vertebral fracture in both sexes. Older age, lower quality of life score on Short Form-12 (physical), past longest occupation as a farmer, and history of cataract were significantly associated with vertebral fracture in females. However, smoking did not appear to be an important risk factor for vertebral fracture. Radiographic assessments for vertebral fracture were performed in all four Asian countries. The prevalence of vertebral fracture was highest in Japan. Lower hip BMD, poorer physical condition and past longest occupation as a farmer were associated with vertebral fracture. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Exercise for improving outcomes after osteoporotic vertebral fracture

PubMed Central

Giangregorio, Lora M; MacIntyre, Norma J; Thabane, Lehana; Skidmore, Carly J; Papaioannou, Alexandra

2016-01-01

Background Vertebral fractures are associated with increased morbidity (e.g., pain, reduced quality of life), and mortality. Therapeutic exercise is a non-pharmacologic conservative treatment that is often recommended for patients with vertebral fractures to reduce pain and restore functional movement. Objectives Our objectives were to evaluate the benefits and harms of exercise interventions of four weeks or greater (alone or as part of a physical therapy intervention) versus non-exercise/non-active physical therapy intervention, no intervention or place boon the incidence of future fractures and adverse events among adults with a history of osteoporotic vertebral fracture(s). We were also examined the effects of exercise on the following secondary outcomes: falls, pain, posture, physical function, balance, mobility, muscle function, quality of life and bone mineral density of the lumbar spine or hip measured using dual-energy X-ray absorptiometry (DXA). We also reported exercise adherence. Search methods We searched the following databases: The Cochrane Library (Issue 11 of 12, November 2011), MEDLINE (2005 to 2011), EMBASE (1988 to November 23, 2011), CINAHL (Cumulative Index to Nursing and Allied Health Literature, 1982 to November 23, 2011), AMED (1985 to November 2011), and PEDro (Physiotherapy Evidence Database, www.pedro.fhs.usyd.edu.au/index.html, 1929 to November 23, 2011. Ongoing and recently completed trials were identified by searching the World Health Organization International Clinical Trials Registry Platform (to December 2009). Conference proceedings were searched via ISI and SCOPUS, and targeted searches of proceedings of the American Congress of Rehabilitation Medicine and American Society for Bone and Mineral Research. Search terms or MeSH headings included terms such as vertebral fracture AND exercise OR physical therapy. Selection criteria We considered all randomized controlled trials and quasi-randomized trials comparing exercise or active

High weight or body mass index increase the risk of vertebral fractures in postmenopausal osteoporotic women.

PubMed

Pirro, Matteo; Fabbriciani, Gianluigi; Leli, Christian; Callarelli, Laura; Manfredelli, Maria Rosaria; Fioroni, Claudio; Mannarino, Massimo Raffaele; Scarponi, Anna Maria; Mannarino, Elmo

2010-01-01

In the general population, low body weight and body mass index (BMI) are significant risk factors for any fracture, but the specific association between body weight, BMI, and prevalence of vertebral fractures in osteoporotic women is not fully recognized. Hence, the association between body weight, BMI, and prevalent vertebral fractures was investigated in 362 women with never-treated postmenopausal osteoporosis. All participants underwent measurement of BMI, bone mineral density (BMD), and semiquantitative assessment of vertebral fractures. Thirty percent of participants had > or =1 vertebral fracture. Body weight and BMI were associated with L1-L4 BMD (R = 0.29, P < 0.001 and R = 0.17, P = 0.009, respectively). In logistic regression analysis, BMI was positively associated with the presence of vertebral fractures independent of age and other traditional risk factors for fractures. Including weight and height instead of BMI in the multivariate model, showed weight as a positive and significant covariate of the presence of vertebral fractures (OR = 1.045; P = 0.016; 95% CI 1.008-1.084). BMI was associated with the number of vertebral fractures (rho = 0.18; P = 0.001), this association being confirmed also in the multivariate analysis (beta = 0.14; P = 0.03) after correction for smoking, early menopause, family history of fragility fractures and BMD. In conclusion, among postmenopausal women with osteoporosis, body weight and BMI are associated with a higher likelihood of having a vertebral fracture, irrespective of the positive association between weight and BMD.

V. Terrestrial vertebrates

Treesearch

Dean Pearson; Deborah Finch

2011-01-01

Within the Interior West, terrestrial vertebrates do not represent a large number of invasive species relative to invasive weeds, aquatic vertebrates, and invertebrates. However, several invasive terrestrial vertebrate species do cause substantial economic and ecological damage in the U.S. and in this region (Pimental 2000, 2007; Bergman and others 2002; Finch and...

A hierarchical 3D segmentation method and the definition of vertebral body coordinate systems for QCT of the lumbar spine.

PubMed

Mastmeyer, André; Engelke, Klaus; Fuchs, Christina; Kalender, Willi A

2006-08-01

We have developed a new hierarchical 3D technique to segment the vertebral bodies in order to measure bone mineral density (BMD) with high trueness and precision in volumetric CT datasets. The hierarchical approach starts with a coarse separation of the individual vertebrae, applies a variety of techniques to segment the vertebral bodies with increasing detail and ends with the definition of an anatomic coordinate system for each vertebral body, relative to which up to 41 trabecular and cortical volumes of interest are positioned. In a pre-segmentation step constraints consisting of Boolean combinations of simple geometric shapes are determined that enclose each individual vertebral body. Bound by these constraints viscous deformable models are used to segment the main shape of the vertebral bodies. Volume growing and morphological operations then capture the fine details of the bone-soft tissue interface. In the volumes of interest bone mineral density and content are determined. In addition, in the segmented vertebral bodies geometric parameters such as volume or the length of the main axes of inertia can be measured. Intra- and inter-operator precision errors of the segmentation procedure were analyzed using existing clinical patient datasets. Results for segmented volume, BMD, and coordinate system position were below 2.0%, 0.6%, and 0.7%, respectively. Trueness was analyzed using phantom scans. The bias of the segmented volume was below 4%; for BMD it was below 1.5%. The long-term goal of this work is improved fracture prediction and patient monitoring in the field of osteoporosis. A true 3D segmentation also enables an accurate measurement of geometrical parameters that may augment the clinical value of a pure BMD analysis.

Vertebrate homologues of Frodo are dynamically expressed during embryonic development in tissues undergoing extensive morphogenetic movements.

PubMed

Hunter, Nina L; Hikasa, Hiroki; Dymecki, Susan M; Sokol, Sergei Y

2006-01-01

Frodo has been identified as a protein interacting with Dishevelled, an essential mediator of the Wnt signaling pathway, critical for the determination of cell fate and polarity in embryonic development. In this study, we use specific gene probes to characterize stage- and tissue-specific expression patterns of the mouse Frodo homologue and compare them with Frodo expression patterns in Xenopus embryos. In situ hybridization analysis of mouse Frodo transcripts demonstrates that, similar to Xenopus Frodo, mouse Frodo is expressed in primitive streak mesoderm, neuroectoderm, neural crest, presomitic mesoderm, and somites. In many cases, Frodo expression is confined to tissues undergoing extensive morphogenesis, suggesting that Frodo may be involved in the regulation of cell shape and motility. Highly conserved dynamic expression patterns of Frodo homologues indicate a similar function for these proteins in different vertebrates. 2005 Wiley-Liss, Inc.

Tegument Protein ORF45 Plays an Essential Role in Virion Morphogenesis of Murine Gammaherpesvirus 68

PubMed Central

Jia, Xing; Shen, Sheng; Lv, Ying; Zhang, Ziwei; Guo, Haitao

2016-01-01

Tegument proteins play critical roles in herpesvirus morphogenesis. ORF45 is a conserved tegument protein of gammaherpesviruses; however, its role in virion morphogenesis is largely unknown. In this work, we determined the ultrastructural localization of murine gammaherpesvirus 68 (MHV-68) ORF45 and found that this protein was incorporated into virions around the site of host-derived vesicles. Notably, the absence of ORF45 inhibited nucleocapsid egress and blocked cytoplasmic virion maturation, demonstrating that ORF45 is essential for MHV-68 virion morphogenesis. PMID:27226376

The ureteric bud epithelium: morphogenesis and roles in metanephric kidney patterning.

PubMed

Nagalakshmi, Vidya K; Yu, Jing

2015-03-01

The mammalian metanephric kidney is composed of two epithelial components, the collecting duct system and the nephron epithelium, that differentiate from two different tissues -the ureteric bud epithelium and the nephron progenitors, respectively-of intermediate mesoderm origin. The collecting duct system is generated through reiterative ureteric bud branching morphogenesis, whereas the nephron epithelium is formed in a process termed nephrogenesis, which is initiated with the mesenchymal-epithelial transition of the nephron progenitors. Ureteric bud branching morphogenesis is regulated by nephron progenitors, and in return, the ureteric bud epithelium regulates nephrogenesis. The metanephric kidney is physiologically divided along the corticomedullary axis into subcompartments that are enriched with specific segments of these two epithelial structures. Here, we provide an overview of the major molecular and cellular processes underlying the morphogenesis and patterning of the ureteric bud epithelium and its roles in the cortico-medullary patterning of the metanephric kidney. © 2015 Wiley Periodicals, Inc.

Morphogenesis by symbiogenesis

NASA Technical Reports Server (NTRS)

Chapman, M. J.; Margulis, L.

1998-01-01

Here we review cases where initiation of morphogenesis, including the differentiation of specialized cells and tissues, has clearly evolved due to cyclical symbiont integration. For reasons of space, our examples are drawn chiefly from the plant, fungal and bacterial kingdoms. Partners live in symbioses and show unique morphological specializations that result when they directly and cyclically interact. We include here brief citations to relevant literature where plant, bacterial or fungal partners alternate independent with entirely integrated living. The independent, or at least physically unassociated stages, are correlated with the appearance of distinctive morphologies that can be traced to the simultaneous presence and strong interaction of the plant with individuals that represent different taxa.

Melatonin Inhibits Embryonic Salivary Gland Branching Morphogenesis by Regulating Both Epithelial Cell Adhesion and Morphology

PubMed Central

Miura, Jiro; Sakai, Manabu; Uchida, Hitoshi; Nakamura, Wataru; Nohara, Kanji; Maruyama, Yusuke; Hattori, Atsuhiko; Sakai, Takayoshi

2015-01-01

Many organs, including salivary glands, lung, and kidney, are formed by epithelial branching during embryonic development. Branching morphogenesis occurs via either local outgrowths or the formation of clefts that subdivide epithelia into buds. This process is promoted by various factors, but the mechanism of branching morphogenesis is not fully understood. Here we have defined melatonin as a potential negative regulator or “brake” of branching morphogenesis, shown that the levels of it and its receptors decline when branching morphogenesis begins, and identified the process that it regulates. Melatonin has various physiological functions, including circadian rhythm regulation, free-radical scavenging, and gonadal development. Furthermore, melatonin is present in saliva and may have an important physiological role in the oral cavity. In this study, we found that the melatonin receptor is highly expressed on the acinar epithelium of the embryonic submandibular gland. We also found that exogenous melatonin reduces salivary gland size and inhibits branching morphogenesis. We suggest that this inhibition does not depend on changes in either proliferation or apoptosis, but rather relates to changes in epithelial cell adhesion and morphology. In summary, we have demonstrated a novel function of melatonin in organ formation during embryonic development. PMID:25876057

Rac1/RhoA antagonism defines cell-to-cell heterogeneity during epidermal morphogenesis in nematodes

PubMed Central

Ouellette, Marie-Hélène

2016-01-01

The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo. Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells. In these contexts, protrusions adopt lamellipodia or an amoeboid morphology. We propose that lamella formation may reduce tension building at cell–cell junctions during morphogenesis. Cell-autonomous antagonism between these pathways enables cells to switch between Rac1- and RhoA-like morphogenetic programs. This study identifies the first case of cell-to-cell heterogeneity controlled by Rac1/RhoA antagonism during epidermal morphogenesis. PMID:27821782

High-resolution-cone beam tomography analysis of bone microarchitecture in patients with acromegaly and radiological vertebral fractures.

PubMed

Maffezzoni, Filippo; Maddalo, Michele; Frara, Stefano; Mezzone, Monica; Zorza, Ivan; Baruffaldi, Fabio; Doglietto, Francesco; Mazziotti, Gherardo; Maroldi, Roberto; Giustina, Andrea

2016-11-01

Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25-72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25-68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and for mineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p < 0.05) lower bone volume/trabecular volume ratio, greater mean trabecular separation, and higher cortical porosity vs. nonfractured patients, without statistically significant differences in mean trabecular thickness and cortical thickness. Fractured and nonfractured acromegaly patients did not have significant differences in bone density at either skeletal site. Patients with acromegaly showed lower bone volume/trabecular volume ratio (p = 0.003) and mean trabecular thickness (p < 0.001) and greater mean trabecular separation (p = 0.02) as compared to control subjects, without significant differences in cortical thickness and porosity. This study shows for the first time that abnormalities of bone microstructure are associated with radiological vertebral fractures in acromegaly. High-resolution cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone

A case report: pregnancy-induced severe osteoporosis with eight vertebral fractures.

PubMed

Ofluoglu, Onder; Ofluoglu, Demet

2008-12-01

Osteoporosis associated with pregnancy and lactation is a rare condition. The prevalence, etiology and its pathogenesis is unknown. It causes one or more vertebral fractures with severe, prolonged back pain and height loss in affected women. Majority of the cases are seen in the third trimester or just after delivery in primagravid women. In this case report, a 30-year-old woman who had severe pregnancy-induced osteoporosis with 8 vertebral fractures was presented. During last month of her first pregnancy she had moderate back pain. After delivery, the back pain has gotten worse. The radiological examinations have shown that there was 50% in T6, T8 and T10; 30% in L2; 20% in L1 height loss and biconcave vertebral images in L3-5. In the bone mineral density, L2-4 T score was -4.7 and total femoral T score was -3.1. There was no abnormality in the laboratory findings except mild elevation in alkaline phosphates. Although pregnancy-associated osteoporosis is a rare condition, when pain occurs in the last trimester or early postpartum period, it should be considered in differential diagnosis.

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis.

PubMed

Rebustini, Ivan T; Myers, Christopher; Lassiter, Keyonica S; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G; Hoffman, Matthew P

2009-10-01

Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression via beta1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis.

Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein

PubMed Central

Heermann, Stephan; Schütz, Lucas; Lemke, Steffen; Krieglstein, Kerstin; Wittbrodt, Joachim

2015-01-01

The hemispheric, bi-layered optic cup forms from an oval optic vesicle during early vertebrate eye development through major morphological transformations. The overall basal surface, facing the developing lens, is increasing, while, at the same time, the space basally occupied by individual cells is decreasing. This cannot be explained by the classical view of eye development. Using zebrafish (Danio rerio) as a model, we show that the lens-averted epithelium functions as a reservoir that contributes to the growing neuroretina through epithelial flow around the distal rims of the optic cup. We propose that this flow couples morphogenesis and retinal determination. Our 4D data indicate that future stem cells flow from their origin in the lens-averted domain of the optic vesicle to their destination in the ciliary marginal zone. BMP-mediated inhibition of the flow results in ectopic neuroretina in the RPE domain. Ultimately the ventral fissure fails to close resulting in coloboma. DOI: http://dx.doi.org/10.7554/eLife.05216.001 PMID:25719386

Osteoporosis and vertebral fractures in men aged 60-74 years.

PubMed

Frost, Morten; Wraae, Kristian; Abrahamsen, Bo; Høiberg, Mikkel; Hagen, Claus; Andersen, Marianne; Brixen, Kim

2012-03-01

limited information on the prevalence of osteoporosis and VFxs in men in high-risk populations is available. The choice of reference values for dual X-ray absorptiometry (DXA) is debated. We evaluated the prevalence of osteoporosis and vertebral deformities in a population-based sample of men. bone mineral density (BMD) was measured and vertebral deformities assessed using DXA and VFx assessment (VFA), respectively, in a random sample of 600 Danish men aged 60-74 years. Osteoporosis was defined as a T-score of -2.5 or less. the study population was comparable with the background population with regard to age, body mass index and co-morbidity. Osteoporosis was diagnosed in less than 1% of the participants at inclusion. Using Danish and NHANES III reference data, 10.2 and 11.5% of the study population had osteoporosis, respectively. In all, 6.3% participants had at least one VFx. BMD was significantly lower in participants with vertebral deformities, but only 24% of these cases had osteoporosis. osteoporosis and VFxs are prevalent in men aged 60-74 years. Although the majority of deformities were present in individuals without osteoporosis, BMD was lower in patients with VFxs at all sites investigated. Male osteoporosis was markedly underdiagnosed.

Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

PubMed

Davidson, Lance A

2011-01-01

Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed. Copyright © 2011 Elsevier Inc. All rights reserved.

Reactive oxygen species in the presence of high glucose alter ureteric bud morphogenesis.

PubMed

Zhang, Shao-Ling; Chen, Yun-Wen; Tran, Stella; Chenier, Isabelle; Hébert, Marie-Josée; Ingelfinger, Julie R

2007-07-01

Renal malformations are a major cause of childhood renal failure. During the development of the kidney, ureteric bud (UB) branching morphogenesis is critical for normal nephrogenesis. These studies investigated whether renal UB branching morphogenesis is altered by a high ambient glucose environment and studied underlying mechanism(s). Kidney explants that were isolated from different periods of gestation (embryonic days 12 to 18) from Hoxb7-green fluorescence protein mice were cultured for 24 h in either normal d-glucose (5 mM) or high d-glucose (25 mM) medium with or without various inhibitors. Alterations in renal morphogenesis were assessed by fluorescence microscopy. Paired-homeobox 2 (Pax-2) gene expression was determined by real-time quantitative PCR, Western blotting, and immunohistology. The results revealed that high d-glucose (25 mM) specifically stimulates UB branching morphogenesis via Pax-2 gene expression, whereas other glucose analogs, such as d-mannitol, l-glucose, and 2-deoxy-d-glucose, had no effect. The stimulatory effect of high glucose on UB branching was blocked in the presence of catalase and inhibitors of NADPH oxidase, mitochondrial electron transport chain complex I, and Akt signaling. Moreover, in in vivo studies, it seems that high glucose induces, via Pax-2 (mainly localized in UB), acceleration of UB branching but not nephron formation. Taken together, these data demonstrate that high glucose alters UB branching morphogenesis. This occurs, at least in part, via reactive oxygen species generation, activation of Akt signaling, and upregulation of Pax-2 gene expression.

Vertebral formula and congenital abnormalities of the vertebral column in rabbits.

PubMed

Proks, P; Stehlik, L; Nyvltova, I; Necas, A; Vignoli, M; Jekl, V

2018-06-01

The aim of this retrospective study of 330 rabbits (164 males, 166 females) was to determine different vertebral formulas and prevalence of congenital vertebral anomalies in rabbits from radiographs of the cervical (C), thoracic (Th), lumbar (L) and sacral (S) segments of the vertebral column. The number of vertebrae in each segment of vertebral column, position of anticlinal vertebra and localisation and type of congenital abnormalities were recorded. In 280/330 rabbits (84.8%) with normal vertebral morphology, seven vertebral formulas were identified: C7/Th12/L7/S4 (252/330, 76.4%), C7/Th12/L6/S4 (11/330, 3.3%), C7/Th13/L7/S4 (8/330, 2.4%), C7/Th12/L7/S5 (4/330, 1.2%), C7/Th12/L8/S4 (3/330, 0.9%), C7/Th12/L7/S6 (1/330, 0.3%) and C7/Th11/L7/S4 (1/330, 0.3%). The anticlinal vertebra was identified as Th10 in 56.4% of rabbits and Th11 in 42.4% of rabbits. Congenital spinal abnormalities were identified in 50/330 (15.2%) rabbits, predominantly as a single pathology (n=44). Transitional vertebrae represented the most common abnormalities (n=41 rabbits) in the thoracolumbar (n=35) and lumbosacral segments (n=6). Five variants of thoracolumbar transitional vertebrae were identified. Cervical butterfly vertebrae were detected in three rabbits. One rabbit exhibited three congenital vertebral anomalies: cervical block vertebra, thoracic hemivertebra and thoracolumbar transitional vertebra. Five rabbits exhibited congenital vertebral abnormalities with concurrent malalignment, specifically cervical kyphosis/short vertebra (n=1), thoracic lordoscoliosis/thoracolumbar transitional vertebrae (n=1), thoracic kyphoscoliosis/wedge vertebrae (n=2) and thoracolumbar lordoscoliosis/thoracolumbar transitional vertebrae/lumbosacral transitional vertebrae (n=1). These findings suggest that vertebral columns in rabbits display a wide range of morphologies, with occasional congenital malformations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of combined teriparatide and zoledronic acid on posterior lumbar vertebral fusion in an aged ovariectomized rat model of osteopenia.

PubMed

Yishake, Mumingjiang; Yasen, Miersalijiang; Jiang, Libo; Liu, Wangmi; Xing, Rong; Chen, Qian; Lin, Hong; Dong, Jian

2018-03-01

There has been no study regarding the effect of a combination of teriparatide (TPTD) and zoledronic acid (ZA) on vertebral fusion. In this study, we investigate the effect of single and combined TPTD and ZA treatment on lumbar vertebral fusion in aged ovariectomized (OVX) rats. Sixty two-month-old female Sprague-Dawley rats were ovariectomized and underwent bilateral L4-L5 posterolateral intertransverse fusion after 10 months. The OVX rats received vehicle (control) treatment, or ZA (100 µg/kg, once), or TPTD (60 µg/kg/2 d for 42 d), or ZA + TPTD until they were euthanized at 6 weeks following lumbar vertebral fusion. The lumbar spine was harvested. Bone mineral density (BMD), bone fusion, bone volume (BV), and bone formation rate (BFR)were analyzed by dual-energy X-ray absorptiometry (DXA), radiography, micro-computed tomography, and histomorphometry. Compared with vehicle (control) treatment, ZA and TPTD monotherapy increased bone volume (BV) at fusion site, and ZA + TPTD combined therapy had an additive effect. Treatment with TPTD and ZA + TPTD increased the bone fusion rate when compared with the control group. ZA monotherapy did not alter the rate of bone fusion. The TPTD and ZA + TPTD treatment groups had increased mineral apposition rate (MAR), mineralizing surfaces/bone surface ((MS/BS), and BFR/BS compared with the OVX group. Our experiment confirm that the monotherapy with TPTD and combination therapy with ZA + TPTD in an OVX rat model of osteopenia following lumbar vertebral fusion surgery increased bone fusion mass and bone fusion rate, and ZA + TPTD combined therapy had an additive effect on bone fusion mass. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:937-944, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The incidence of secondary vertebral fracture of vertebral augmentation techniques versus conservative treatment for painful osteoporotic vertebral fractures: a systematic review and meta-analysis.

PubMed

Song, Dawei; Meng, Bin; Gan, Minfeng; Niu, Junjie; Li, Shiyan; Chen, Hao; Yuan, Chenxi; Yang, Huilin

2015-08-01

Percutaneous vertebroplasty (PVP) and balloon kyphoplasty (BKP) are minimally invasive and effective vertebral augmentation techniques for managing osteoporotic vertebral compression fractures (OVCFs). Recent meta-analyses have compared the incidence of secondary vertebral fractures between patients treated with vertebral augmentation techniques or conservative treatment; however, the inclusions were not thorough and rigorous enough, and the effects of each technique on the incidence of secondary vertebral fractures remain unclear. To perform an updated systematic review and meta-analysis of the studies with more rigorous inclusion criteria on the effects of vertebral augmentation techniques and conservative treatment for OVCF on the incidence of secondary vertebral fractures. PubMed, MEDLINE, EMBASE, SpringerLink, Web of Science, and the Cochrane Library database were searched for relevant original articles comparing the incidence of secondary vertebral fractures between vertebral augmentation techniques and conservative treatment for patients with OVCFs. Randomized controlled trials (RCTs) and prospective non-randomized controlled trials (NRCTs) were identified. The methodological qualities of the studies were evaluated, relevant data were extracted and recorded, and an appropriate meta-analysis was conducted. A total of 13 articles were included. The pooled results from included studies showed no statistically significant differences in the incidence of secondary vertebral fractures between patients treated with vertebral augmentation techniques and conservative treatment. Subgroup analysis comparing different study designs, durations of symptoms, follow-up times, races of patients, and techniques were conducted, and no significant differences in the incidence of secondary fractures were identified (P > 0.05). No obvious publication bias was detected by either Begg's test (P = 0.360 > 0.05) or Egger's test (P = 0.373 > 0.05). Despite current thinking in the

Rap1 GTPase is required for mouse lens epithelial maintenance and morphogenesis

PubMed Central

Maddala, Rupalatha; Nagendran, Tharkika; Lang, Richard A.; Morozov, Alexei; Rao, Ponugoti V.

2015-01-01

Rap1, a Ras-like small GTPase, plays a crucial role in cell-matrix adhesive interactions, cell-cell junction formation, cell polarity and migration. The role of Rap1 in vertebrate organ development and tissue architecture, however, remains elusive. We addressed this question in a mouse lens model system using a conditional gene targeting approach. While individual germline deficiency of either Rap1a or Rap1b did not cause overt defects in mouse lens, conditional double deficiency (Rap1 cKO) prior to lens placode formation led to an ocular phenotype including microphthalmia and lens opacification in embryonic mice. The embryonic Rap1 cKO mouse lens exhibited striking defects including loss of E-cadherin- and ZO-1-based cell-cell junctions, disruption of paxillin and β1-integrin-based cell adhesive interactions along with abnormalities in cell shape and apical-basal polarity of epithelium. These epithelial changes were accompanied by increased levels of α-smooth muscle actin, vimentin and N-cadherin, and expression of transcriptional suppressors of E-cadherin (Snai1, Slug and Zeb2), and a mesenchymal metabolic protein (Dihydropyrimidine dehydrogenase). Additionally, while lens differentiation was not overtly affected, increased apoptosis and dysregulated cell cycle progression were noted in epithelium and fibers in Rap1 cKO mice. Collectively these observations uncover a requirement for Rap1 in maintenance of lens epithelial phenotype and morphogenesis. PMID:26212757

Modulation of Morphogenesis in Candida albicans by Various Small Molecules ▿

PubMed Central

Shareck, Julie; Belhumeur, Pierre

2011-01-01

The pathogenic yeast Candida albicans, a member of the mucosal microbiota, is responsible for a large spectrum of infections, ranging from benign thrush and vulvovaginitis in both healthy and immunocompromised individuals to severe, life-threatening infections in immunocompromised patients. A striking feature of C. albicans is its ability to grow as budding yeast and as filamentous forms, including hyphae and pseudohyphae. The yeast-to-hypha transition contributes to the overall virulence of C. albicans and may even constitute a target for the development of antifungal drugs. Indeed, impairing morphogenesis in C. albicans has been shown to be a means to treat candidiasis. Additionally, a large number of small molecules such as farnesol, fatty acids, rapamycin, geldanamycin, histone deacetylase inhibitors, and cell cycle inhibitors have been reported to modulate the yeast-to-hypha transition in C. albicans. In this minireview, we take a look at molecules that modulate morphogenesis in this pathogenic yeast. When possible, we address experimental findings regarding their mechanisms of action and their therapeutic potential. We discuss whether or not modulating morphogenesis constitutes a strategy to treat Candida infections. PMID:21642508

Polycystin-1 Binds Par3/aPKC and Controls Convergent Extension During Renal Tubular Morphogenesis

PubMed Central

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-01-01

Several organs, including lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintanance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1 (PC-1), a large receptor of unknown function. Here we demonstrate that PC-1 plays an essential role in establishment of correct tubular diameter during nephron development. PC-1 associates with Par3 favoring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a program of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis and in renal cyst formation. Our data define PC-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis. PMID:24153433

Polycystin-1 binds Par3/aPKC and controls convergent extension during renal tubular morphogenesis

NASA Astrophysics Data System (ADS)

Castelli, Maddalena; Boca, Manila; Chiaravalli, Marco; Ramalingam, Harini; Rowe, Isaline; Distefano, Gianfranco; Carroll, Thomas; Boletta, Alessandra

2013-10-01

Several organs, including the lungs and kidneys, are formed by epithelial tubes whose proper morphogenesis ensures correct function. This is best exemplified by the kidney, where defective establishment or maintenance of tubular diameter results in polycystic kidney disease, a common genetic disorder. Most polycystic kidney disease cases result from loss-of-function mutations in the PKD1 gene, encoding Polycystin-1, a large receptor of unknown function. Here we demonstrate that PC-1 has an essential role in the establishment of correct tubular diameter during nephron development. Polycystin-1 associates with Par3 favouring the assembly of a pro-polarizing Par3/aPKC complex and it regulates a programme of cell polarity important for oriented cell migration and for a convergent extension-like process during tubular morphogenesis. Par3 inactivation in the developing kidney results in defective convergent extension and tubular morphogenesis, and in renal cyst formation. Our data define Polycystin-1 as central to cell polarization and to epithelial tube morphogenesis and homeostasis.

The Polarity Protein Partitioning-defective 1 (PAR-1) Regulates Dendritic Spine Morphogenesis through Phosphorylating Postsynaptic Density Protein 95 (PSD-95)*

PubMed Central

Wu, Qian; DiBona, Victoria L.; Bernard, Laura P.; Zhang, Huaye

2012-01-01

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95. PMID:22807451

The polarity protein partitioning-defective 1 (PAR-1) regulates dendritic spine morphogenesis through phosphorylating postsynaptic density protein 95 (PSD-95).

PubMed

Wu, Qian; DiBona, Victoria L; Bernard, Laura P; Zhang, Huaye

2012-08-31

The polarity protein PAR-1 plays an essential role in many cellular contexts, including embryogenesis, asymmetric cell division, directional migration, and epithelial morphogenesis. Despite its known importance in different cellular processes, the role of PAR-1 in neuronal morphogenesis is less well understood. In particular, its role in the morphogenesis of dendritic spines, which are sites of excitatory synaptic inputs, has been unclear. Here, we show that PAR-1 is required for normal spine morphogenesis in hippocampal neurons. We further show that PAR-1 functions through phosphorylating the synaptic scaffolding protein PSD-95 in this process. Phosphorylation at a conserved serine residue in the KXGS motif in PSD-95 regulates spine morphogenesis, and a phosphomimetic mutant of this site can rescue the defects of kinase-dead PAR-1. Together, our findings uncover a role of PAR-1 in spine morphogenesis in hippocampal neurons through phosphorylating PSD-95.

Adjacent vertebral body fracture following vertebroplasty with polymethylmethacrylate or calcium phosphate cement: biomechanical evaluation of the cadaveric spine.

PubMed

Nouda, Shinya; Tomita, Seiji; Kin, Akihiro; Kawahara, Kunihiko; Kinoshita, Mitsuo

2009-11-15

A biomechanical study using human cadaveric thoracolumbar spinal columns. To compare the effect of treatment by vertebroplasty (VP) with polymethylmethacrylate cement and VP with calcium phosphate cement on the creation of adjacent vertebral body fracture following VP. Adjacent vertebral body fractures have been reported as a complication following VP. Twenty-four spinal columns (T10-L2) from human cadavers were subjected to dual energy radiograph absorptiometry to assess bone mineral density. They were divided into the P group and C group, and experimental vertebral compression fractures were created at T12 vertebrae. T12 vertebrae were augmented with polymethylmethacrylate and calcium phosphate cement in the P group and C group, respectively. Each spinal column was compressed until a new fracture occurred at any vertebra, and the location of newly fractured vertebra and failure load was investigated. There was no significant difference in bone mineral density at each level within each group. In the P group, a new fracture occurred at T10 in 2 specimens, T11 in 8, and L1 in 2. In the C group, it occurred at T10 in 1 specimen, T11 in 2, L1 in 1, and T12 (treated vertebra) in 8. The failure loads of the spinal column were 1774.8+/-672.3 N and 1501.2+/-556.5 N in the P group and C group, respectively. There was no significant difference in the failure load of the spinal column between each group. New vertebral fractures occurred at the vertebra adjacent to augmented vertebrae in the P group and in the augmented vertebrae in the C group. The difference in the fractured site may be because of the difference in strength between the 2 bone filler materials. Therefore, the strength of bone filler materials is considered a risk factor in developing adjacent vertebral body fractures after VP.

MT2-MMP-dependent release of collagen IV NC1 domains regulates submandibular gland branching morphogenesis

PubMed Central

Rebustini, Ivan T.; Myers, Christopher; Lassiter, Keyonica S.; Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn; Pedchenko, Vadim; Hudson, Billy G.; Hoffman, Matthew P.

2009-01-01

Summary Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Importantly, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA-treatment, increasing MT-MMP and pro-proliferative gene expression via β1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA-treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. PMID:19853562

klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis

PubMed Central

Steed, Emily; Faggianelli, Nathalie; Roth, Stéphane; Ramspacher, Caroline; Concordet, Jean-Paul; Vermot, Julien

2016-01-01

The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis. PMID:27221222

The TINS Lecture. Understanding the roles of Otx1 and Otx2 in the control of brain morphogenesis.

PubMed

Acampora, D; Simeone, A

1999-03-01

The murine homologs of the orthodenticle (otd) gene of Drosophila, Otx1 and Otx2, have an important role in brain morphogenesis. Analysis of Otx1 and Otx2 null mice reveals that Otx1 is required primarily for corticogenesis and sense-organ development,while Otx2 is necessary for specification and maintenance of anterior neural plate as well as for proper gastrulation. Cross-phylum recoveries of Otx1 abnormalities by Drosophila otd, and vice versa, indicate that genetic functions required in mammalian-brain development evolved in a primitive ancestor of flies and mice. Knock-in mouse models in which Otx2 was replaced with Otx1, and vice versa, provide evidence that the existence of Otx1-/- and Otx2-/- divergent phenotypes largely reflects differences in expression patterns rather than in the biochemical activity of OTX1 and OTX2. In evolutionary terms, some of these findings lead us to hypothesize a fascinating and crucial role for Otx genes that contributes to the genetic program required for the specification of the development of the vertebrate head.

Adenosine Kinase Modulates Root Gravitropism and Cap Morphogenesis in Arabidopsis1[W][OA

PubMed Central

Young, Li-Sen; Harrison, Benjamin R.; U.M., Narayana Murthy; Moffatt, Barbara A.; Gilroy, Simon; Masson, Patrick H.

2006-01-01

Adenosine kinase (ADK) is a key enzyme that regulates intra- and extracellular levels of adenosine, thereby modulating methyltransferase reactions, production of polyamines and secondary compounds, and cell signaling in animals. Unfortunately, little is known about ADK's contribution to the regulation of plant growth and development. Here, we show that ADK is a modulator of root cap morphogenesis and gravitropism. Upon gravistimulation, soluble ADK levels and activity increase in the root tip. Mutation in one of two Arabidopsis (Arabidopsis thaliana) ADK genes, ADK1, results in cap morphogenesis defects, along with alterations in root sensitivity to gravistimulation and slower kinetics of root gravitropic curvature. The kinetics defect can be partially rescued by adding spermine to the growth medium, whereas the defects in cap morphogenesis and gravitropic sensitivity cannot. The root morphogenesis and gravitropism defects of adk1-1 are accompanied by altered expression of the PIN3 auxin efflux facilitator in the cap and decreased expression of the auxin-responsive DR5-GUS reporter. Furthermore, PIN3 fails to relocalize to the bottom membrane of statocytes upon gravistimulation. Consequently, adk1-1 roots cannot develop a lateral auxin gradient across the cap, necessary for the curvature response. Interestingly, adk1-1 does not affect gravity-induced cytoplasmic alkalinization of the root statocytes, suggesting either that ADK1 functions between cytoplasmic alkalinization and PIN3 relocalization in a linear pathway or that the pH and PIN3-relocalization responses to gravistimulation belong to distinct branches of the pathway. Our data are consistent with a role for ADK and the S-adenosyl-l-methionine pathway in the control of root gravitropism and cap morphogenesis. PMID:16891550

Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids.

PubMed

Linch, Mark; Sanz-Garcia, Marta; Rosse, Carine; Riou, Philippe; Peel, Nick; Madsen, Chris D; Sahai, Erik; Downward, Julian; Khwaja, Asim; Dillon, Christian; Roffey, Jon; Cameron, Angus J M; Parker, Peter J

2014-02-01

Protein kinase C iota (PKCι), a serine/threonine kinase required for cell polarity, proliferation and migration, is commonly up- or downregulated in cancer. PKCι is a human oncogene but whether this is related to its role in cell polarity and what repertoire of oncogenes acts in concert with PKCι is not known. We developed a panel of candidate oncogene expressing Madin-Darby canine kidney (MDCK) cells and demonstrated that H-Ras, ErbB2 and phosphatidylinositol 3-kinase transformation led to non-polar spheroid morphogenesis (dysplasia), whereas MDCK spheroids expressing c-Raf or v-Src were largely polarized. We show that small interfering RNA (siRNA)-targeting PKCι decreased the size of all spheroids tested and partially reversed the aberrant polarity phenotype in H-Ras and ErbB2 spheroids only. This indicates distinct requirements for PKCι and moreover that different thresholds of PKCι activity are required for these phenotypes. By manipulating PKCι function using mutant constructs, siRNA depletion or chemical inhibition, we have demonstrated that PKCι is required for polarization of parental MDCK epithelial cysts in a 3D matrix and that there is a threshold of PKCι activity above and below which, disorganized epithelial morphogenesis results. Furthermore, treatment with a novel PKCι inhibitor, CRT0066854, was able to restore polarized morphogenesis in the dysplastic H-Ras spheroids. These results show that tightly regulated PKCι is required for normal-polarized morphogenesis in mammalian cells and that H-Ras and ErbB2 cooperate with PKCι for loss of polarization and dysplasia. The identification of a PKCι inhibitor that can restore polarized morphogenesis has implications for the treatment of Ras and ErbB2 driven malignancies.

Morphogenesis in Plants: Modeling the Shoot Apical Meristem, and Possible Applications

NASA Technical Reports Server (NTRS)

Mjolsness, Eric; Gor, Victoria; Meyerowitz, Elliot; Mann, Tobias

1998-01-01

A key determinant of overall morphogenesis in flowering plants such as Arabidopsis thaliana is the shoot apical meristem (growing tip of a shoot). Gene regulation networks can be used to model this system. We exhibit a very preliminary two-dimensional model including gene regulation and intercellular signaling, but omitting cell division and dynamical geometry. The model can be trained to have three stable regions of gene expression corresponding to the central zone, peripheral zone, and rib meristem. We also discuss a space-engineering motivation for studying and controlling the morphogenesis of plants using such computational models.

Determinants of Microdamage in Elderly Human Vertebral Trabecular Bone

PubMed Central

Follet, Hélène; Farlay, Delphine; Bala, Yohann; Viguet-Carrin, Stéphanie; Gineyts, Evelyne; Burt-Pichat, Brigitte; Wegrzyn, Julien; Delmas, Pierre; Boivin, Georges; Chapurlat, Roland

2013-01-01

Previous studies have shown that microdamage accumulates in bone as a result of physiological loading and occurs naturally in human trabecular bone. The purpose of this study was to determine the factors associated with pre-existing microdamage in human vertebral trabecular bone, namely age, architecture, hardness, mineral and organic matrix. Trabecular bone cores were collected from human L2 vertebrae (n = 53) from donors 54–95 years of age (22 men and 30 women, 1 unknown) and previous cited parameters were evaluated. Collagen cross-link content (PYD, DPD, PEN and % of collagen) was measured on surrounding trabecular bone. We found that determinants of microdamage were mostly the age of donors, architecture, mineral characteristics and mature enzymatic cross-links. Moreover, linear microcracks were mostly associated with the bone matrix characteristics whereas diffuse damage was associated with architecture. We conclude that linear and diffuse types of microdamage seemed to have different determinants, with age being critical for both types. PMID:23457465

Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa.

PubMed

Bachmann, Katherine N; Schorr, Melanie; Bruno, Alexander G; Bredella, Miriam A; Lawson, Elizabeth A; Gill, Corey M; Singhal, Vibha; Meenaghan, Erinne; Gerweck, Anu V; Slattery, Meghan; Eddy, Kamryn T; Ebrahimi, Seda; Koman, Stuart L; Greenblatt, James M; Keane, Robert J; Weigel, Thomas; Misra, Madhusmita; Bouxsein, Mary L; Klibanski, Anne; Miller, Karen K

2017-01-01

Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including "atypical" AN [body mass index (BMI) ≥18.5 kg/m2]. To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum. Cross-sectional observational study. Clinical research center. 153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2). Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA). Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone. Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength. Copyright © 2017 by the Endocrine Society

Vertebral Volumetric Bone Density and Strength Are Impaired in Women With Low-Weight and Atypical Anorexia Nervosa

PubMed Central

Bachmann, Katherine N.; Schorr, Melanie; Bruno, Alexander G.; Bredella, Miriam A.; Lawson, Elizabeth A.; Gill, Corey M.; Singhal, Vibha; Meenaghan, Erinne; Gerweck, Anu V.; Slattery, Meghan; Eddy, Kamryn T.; Ebrahimi, Seda; Koman, Stuart L.; Greenblatt, James M.; Keane, Robert J.; Weigel, Thomas; Misra, Madhusmita; Bouxsein, Mary L.; Klibanski, Anne

2017-01-01

Context: Areal bone mineral density (BMD) is lower, particularly at the spine, in low-weight women with anorexia nervosa (AN). However, little is known about vertebral integral volumetric BMD (Int.vBMD) or vertebral strength across the AN weight spectrum, including “atypical” AN [body mass index (BMI) ≥18.5 kg/m2]. Objective: To investigate Int.vBMD and vertebral strength, and their determinants, across the AN weight spectrum Design: Cross-sectional observational study Setting: Clinical research center Participants: 153 women (age 18 to 45): 64 with low-weight AN (BMI <18.5 kg/m2; 58% amenorrheic), 44 with atypical AN (18.5≤BMI<23 kg/m2; 30% amenorrheic), 45 eumenorrheic controls (19.2≤BMI<25 kg/m2). Measures: Int.vBMD and cross-sectional area (CSA) by quantitative computed tomography of L4; estimated vertebral strength (derived from Int.vBMD and CSA) Results: Int.vBMD and estimated vertebral strength were lowest in low-weight AN, intermediate in atypical AN, and highest in controls. CSA did not differ between groups; thus, vertebral strength (calculated using Int.vBMD and CSA) was driven by Int.vBMD. In AN, Int.vBMD and vertebral strength were associated positively with current BMI and nadir lifetime BMI (independent of current BMI). Int.vBMD and vertebral strength were lower in AN with current amenorrhea and longer lifetime amenorrhea duration. Among amenorrheic AN, Int.vBMD and vertebral strength were associated positively with testosterone. Conclusions: Int.vBMD and estimated vertebral strength (driven by Int.vBMD) are impaired across the AN weight spectrum and are associated with low BMI and endocrine dysfunction, both current and previous. Women with atypical AN experience diminished vertebral strength, partially due to prior low-weight and/or amenorrhea. Lack of current low-weight or amenorrhea in atypical AN does not preclude compromise of vertebral strength. PMID:27732336

Regeneration, morphogenesis and self-organization.

PubMed

Goldman, Daniel

2014-07-01

The RIKEN Center for Developmental Biology in Kobe, Japan, hosted a meeting entitled 'Regeneration of Organs: Programming and Self-Organization' in March, 2014. Scientists from across the globe met to discuss current research on regeneration, organ morphogenesis and self-organization - and the links between these fields. A diverse range of experimental models and organ systems was presented, and the speakers aptly illustrated the unique power of each. This Meeting Review describes the major advances reported and themes emerging from this exciting meeting. © 2014. Published by The Company of Biologists Ltd.

Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.

PubMed

Barriga, Elias H; Franze, Kristian; Charras, Guillaume; Mayor, Roberto

2018-02-22

Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiates an epithelial-to-mesenchymal transition in neural crest cells and triggers their collective migration. To detect changes in their mechanical environment, neural crest cells use mechanosensation mediated by the integrin-vinculin-talin complex. By performing mechanical and molecular manipulations, we show that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrate that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results show that convergent extension of the mesoderm has a role as a mechanical coordinator of morphogenesis, and reveal a link between two apparently unconnected processes-gastrulation and neural crest migration-via changes in tissue mechanics. Overall, we demonstrate that changes in substrate stiffness can trigger collective cell migration by promoting epithelial-to-mesenchymal transition in vivo. More broadly, our results raise the idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.

Binding of Glutathione to Enterovirus Capsids Is Essential for Virion Morphogenesis

PubMed Central

Thibaut, Hendrik Jan; Thys, Bert; Canela, María-Dolores; Aguado, Leire; Wimmer, Eckard; Paul, Aniko; Pérez-Pérez, María-Jesús; van Kuppeveld, Frank J. M.; Neyts, Johan

2014-01-01

Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We report the discovery of TP219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds directly glutathione (GSH), thereby rapidly depleting intracellular GSH levels and that this interferes with virus morphogenesis without affecting viral RNA replication. The inhibitory effect on assembly was shown not to depend on an altered reducing environment. Using TP219, we show that GSH is an essential stabilizing cofactor during the transition of protomeric particles into pentameric particles. Sequential passaging of coxsackievirus B3 in the presence of low GSH-levels selected for GSH-independent mutants that harbored a surface-exposed methionine in VP1 at the interface between two protomers. In line with this observation, enteroviruses that already contained this surface-exposed methionine, such as EV71, did not rely on GSH for virus morphogenesis. Biochemical and microscopical analysis provided strong evidence for a direct interaction between GSH and wildtype VP1 and a role for this interaction in localizing assembly intermediates to replication sites. Consistently, the interaction between GSH and mutant VP1 was abolished resulting in a relocalization of the assembly intermediates to replication sites independent from GSH. This study thus reveals GSH as a novel stabilizing host factor essential for the production of infectious enterovirus progeny and provides new insights into the poorly understood process of morphogenesis. PMID:24722756

Review of aragonite and calcite crystal morphogenesis in thermal spring systems

NASA Astrophysics Data System (ADS)

Jones, Brian

2017-06-01

Aragonite and calcite crystals are the fundamental building blocks of calcareous thermal spring deposits. The diverse array of crystal morphologies found in these deposits, which includes monocrystals, mesocrystals, skeletal crystals, dendrites, and spherulites, are commonly precipitated under far-from-equilibrium conditions. Such crystals form through both abiotic and biotic processes. Many crystals develop through non-classical crystal growth models that involve the arrangement of nanocrystals in a precisely controlled crystallographic register. Calcite crystal morphogenesis has commonly been linked to a ;driving force;, which is a conceptual measure of the distance of the growth conditions from equilibrium conditions. Essentially, this scheme indicates that increasing levels of supersaturation and various other parameters that produce a progressive change from monocrystals and mesocrystals to skeletal crystals to crystallographic and non-crystallographic dendrites, to dumbbells, to spherulites. Despite the vast amount of information available from laboratory experiments and natural spring systems, the precise factors that control the driving force are open to debate. The fact that calcite crystal morphogenesis is still poorly understood is largely a reflection of the complexity of the factors that influence aragonite and calcite precipitation. Available information indicates that variations in calcite crystal morphogenesis can be attributed to physical and chemical parameters of the parent water, the presence of impurities, the addition of organic or inorganic additives to the water, the rate of crystal growth, and/or the presence of microbes and their associated biofilms. The problems in trying to relate crystal morphogenesis to specific environmental parameters arise because it is generally impossible to disentangle the controlling factor(s) from the vast array of potential parameters that may act alone or in unison with each other.

Anthropometric measurements and vertebral deformities. European Vertebral Osteoporosis Study (EVOS) Group.

PubMed

Johnell, O; O'Neill, T; Felsenberg, D; Kanis, J; Cooper, C; Silman, A J

1997-08-15

To investigate the association between anthropometric indices and morphometrically determined vertebral deformity, the authors carried out a cross-sectional study using data from the European Vertebral Osteoporosis Study (EVOS), a population-based study of vertebral osteoporosis in 36 European centers from 19 countries. A total of 16,047 EVOS subjects were included in this analysis, of whom 1,973 subjects (915 males, 1,058 females) (12.3%) aged 50 years or over had one or more vertebral deformities ("cases"). The cases were compared with the 14,074 subjects (6,539 males, 7,535 females) with morphometrically normal spines ("controls"). Data were collected on self-reported height at age 25 years and minimum weight after age 25 years, as well as on current measured height and weight. Body mass index (BMI) and height and weight change were calculated from these data. The relations between these variables and vertebral deformity were examined separately by sex with logistic regression adjusting for age, smoking, and physical activity. In females, there was a significant trend of decreasing risk with increasing quintile of current weight, current BMI, and weight gain since age 25 years. In males, subjects in the lightest quintile for these measures were at increased risk but there was no evidence of a trend. An ecologic analysis by country revealed a negative correlation between mean BMI and the prevalence of deformity in females but not in males. The authors conclude that low body weight is associated with presence of vertebral deformity.

Polarized protein transport and lumen formation during epithelial tissue morphogenesis.

PubMed

Blasky, Alex J; Mangan, Anthony; Prekeris, Rytis

2015-01-01

One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo.

Evolution and development of the vertebrate ear

NASA Technical Reports Server (NTRS)

Fritzsch, B.; Beisel, K. W.

2001-01-01

This review outlines major aspects of development and evolution of the ear, specifically addressing issues of cell fate commitment and the emerging molecular governance of these decisions. Available data support the notion of homology of subsets of mechanosensors across phyla (proprioreceptive mechanosensory neurons in insects, hair cells in vertebrates). It is argued that this conservation is primarily related to the specific transducing environment needed to achieve mechanosensation. Achieving this requires highly conserved transcription factors that regulate the expression of the relevant structural genes for mechanosensory transduction. While conserved at the level of some cell fate assignment genes (atonal and its mammalian homologue), the ear has also radically reorganized its development by implementing genes used for cell fate assignment in other parts of the developing nervous systems (e.g., neurogenin 1) and by evolving novel sets of genes specifically associated with the novel formation of sensory neurons that contact hair cells (neurotrophins and their receptors). Numerous genes have been identified that regulate morphogenesis, but there is only one common feature that emerges at the moment: the ear appears to have co-opted genes from a large variety of other parts of the developing body (forebrain, limbs, kidneys) and establishes, in combination with existing transcription factors, an environment in which those genes govern novel, ear-related morphogenetic aspects. The ear thus represents a unique mix of highly conserved developmental elements combined with co-opted and newly evolved developmental elements.

Evolution of endothelin receptors in vertebrates.

PubMed

Braasch, Ingo; Schartl, Manfred

2014-12-01

Endothelin receptors are G protein coupled receptors (GPCRs) of the β-group of rhodopsin receptors that bind to endothelin ligands, which are 21 amino acid long peptides derived from longer prepro-endothelin precursors. The most basal Ednr-like GPCR is found outside vertebrates in the cephalochordate amphioxus, but endothelin ligands are only present among vertebrates, including the lineages of jawless vertebrates (lampreys and hagfishes), cartilaginous vertebrates (sharks, rays, and chimaeras), and bony vertebrates (ray-finned fishes and lobe-finned vertebrates including tetrapods). A bona fide endothelin system is thus a vertebrate-specific innovation with important roles for regulating the cardiovascular system, renal and pulmonary processes, as well as for the development of the vertebrate-specific neural crest cell population and its derivatives. Expectedly, dysregulation of endothelin receptors and the endothelin system leads to a multitude of human diseases. Despite the importance of different types of endothelin receptors for vertebrate development and physiology, current knowledge on endothelin ligand-receptor interactions, on the expression of endothelin receptors and their ligands, and on the functional roles of the endothelin system for embryonic development and in adult vertebrates is very much biased towards amniote vertebrates. Recent analyses from a variety of vertebrate lineages, however, have shown that the endothelin system in lineages such as teleost fish and lampreys is more diverse and is divergent from the mammalian endothelin system. This diversity is mainly based on differential evolution of numerous endothelin system components among vertebrate lineages generated by two rounds of whole genome duplication (three in teleosts) during vertebrate evolution. Here we review current understanding of the evolutionary history of the endothelin receptor family in vertebrates supplemented with surveys on the endothelin receptor gene complement of

Synthesis and morphogenesis of organic and inorganic polymers by means of biominerals and biomimetic materials.

PubMed

Kijima, Misako; Oaki, Yuya; Munekawa, Yurika; Imai, Hiroaki

2013-02-11

We have studied the simultaneous synthesis and morphogenesis of polymer materials with hierarchical structures from nanoscopic to macroscopic scales. The morphologies of the original materials can be replicated to the polymer materials. In general, it is not easy to achieve the simultaneous synthesis and morphogenesis of polymer material even using host materials. In the present work, four biominerals and three biomimetic mesocrystal structures are used as the host materials or templates and polypyrrole, poly(3-hexylthiopehene), and silica were used as the precursors for the simultaneous syntheses and morphogenesis of polymer materials. The host materials with the hierarchical structure possess the nanospace for the incorporation of the monomers. After the incorporation of the monomers, the polymerization reaction proceeds in the nanospace with addition of the initiator agents. Then, the dissolution of the host materials leads to the formation and morphogenesis of the polymer materials. The scheme of the replication can be classified into the three types based on the structures of the host materials (types I-III). The type I template facilitates the hierarchical replication of the whole host material, type II mediates the hierarchical surface replication, and type III induces the formation of the two-dimensional nanosheets. Based on these results, the approach for the coupled synthesis and morphogenesis can be applied to a variety of combinations of the templates and polymer materials. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bone-density-specific fracture risk: A population-based study of the relationship between osteoporosis and vertebral fractures

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

Melton, L.J.; Wahner, H.W.; Richelson, L.S.

The search for a specific level of bone density that clearly distinguishes patients with osteoporosis from those without has been largely unsuccessful. A different, ''gradient of risk'' model was used to assess the effect of various degrees of osteoporosis on the prevalence of vertebral fractures. The authors measured spinal (L/sub 1/-L/sub 4/) bone mineral (BM) with dual photon absorptiometry in an age-stratified random sample of Rochester, Minnesota women greater than or equal to 35 years old to estimate the distribution of spinal BM in the population of adult woman. The authors also assessed BM among women in the sample whomore » had one or more vertebral fractures to estimate both the total number of women with vertebral fractures in the population and the distribution of spinal BM in such women. These population-based estimates were then used to calculate the prevalence rate of vertebral fracture at various levels of spinal BM. Women with spinal BM greater than or equal to 1.40 g/cm/sup 2/ were free of vertebral fractures. Among women with BM between 1.00 and 1.39 g/cm/sup 2/, the prevalence of vertebral fractures was about 7%. The prevalence rate increased as spinal BM decreased further. Among women with spinal BM<0.60 g/cm/sup 2/, all had at least one vertebral fracture (prevalence=100%). These data indicate that osteoporosis is a necessary cause of age-related vertebral fractures and, at certain low levels, is a sufficient cause of such fractures in conjunction with the activities of daily living.« less

Gonadal morphogenesis and gene expression in reptiles with temperature-dependent sex determination.

PubMed

Merchant-Larios, H; Díaz-Hernández, V; Marmolejo-Valencia, A

2010-01-01

In reptiles with temperature-dependent sexual determination, the thermosensitive period (TSP) is the interval in which the sex is defined during gonadal morphogenesis. One-shift experiments in a group of eggs define the onset and the end of the TSP as all and none responses, respectively. Timing for sex-undetermined (UG) and -determined gonads (DG) differs at male- (MPT) or female-producing temperatures (FPT). During the TSP a decreasing number of embryos respond to temperature shifts indicating that in this period embryos with both UG and DG exist. Although most UG correspond to undifferentiated gonads, some embryos extend UG after the onset of histological differentiation. Thus, temperature affects gonadal cells during the process of morphogenesis, but timing of commitment depends on individual embryos. A correlation between gonadal morphogenesis, TSP, and gene expression suggests that determination of the molecular pathways modulated by temperature in epithelial cells (surface epithelium and medullary cords) holds the key for a unifying hypothesis on temperature-dependent sex determination. (c) 2010 S. Karger AG, Basel.

Vertebral stabilization using positively threaded profile pins and polymethylmethacrylate, with or without laminectomy, for spinal canal stenosis and vertebral instability caused by congenital thoracic vertebral anomalies.

PubMed

Aikawa, Takeshi; Kanazono, Shinichi; Yoshigae, Yuki; Sharp, Nicholas J H; Muñana, Karen R

2007-07-01

To describe diagnostic findings, surgical technique, and outcome in dogs with thoracic spinal canal stenosis and vertebral instability secondary to congenital vertebral anomalies. Retrospective clinical study. Dogs (n=9) with thoracic spinal canal stenosis. Medical records (1995-1996; 2000-2006) of 9 dogs with a myelographic diagnosis of spinal canal stenosis and/or vertebral instability secondary to congenital vertebral anomaly that were surgically managed by vertebral stabilization with or without laminectomy were reviewed. Data on pre- and postoperative neurologic status, diagnostic findings, surgical techniques, and outcomes were retrieved. Follow-up evaluations were performed at 1, 2, and 6 months. Long-term outcome was assessed by means of clinical examination or owner telephone interviews. Spinal cord compression was confirmed by myelography, and in 2 dogs, dynamic compression by stress myelography. Eight dogs regained the ability to ambulate postoperatively. One dog with a partial recovery regained voluntary movement but did not become ambulatory. Spinal cord injury secondary to congenital vertebral anomaly may have a good outcome when treated by vertebral stabilization with or without laminectomy. Adequate stabilization of the vertebrae and improved neurologic outcome were achieved in most dogs. Vertebral stabilization using positively threaded profile pins and polymethylmethacrylate with or without laminectomy is an effective treatment for spinal canal stenosis and vertebral instability secondary to congenital thoracic vertebral anomalies.

A review of phosphate mineral nucleation in biology and geobiology.

PubMed

Omelon, Sidney; Ariganello, Marianne; Bonucci, Ermanno; Grynpas, Marc; Nanci, Antonio

2013-10-01

Relationships between geological phosphorite deposition and biological apatite nucleation have often been overlooked. However, similarities in biological apatite and phosphorite mineralogy suggest that their chemical formation mechanisms may be similar. This review serves to draw parallels between two newly described phosphorite mineralization processes, and proposes a similar novel mechanism for biologically controlled apatite mineral nucleation. This mechanism integrates polyphosphate biochemistry with crystal nucleation theory. Recently, the roles of polyphosphates in the nucleation of marine phosphorites were discovered. Marine bacteria and diatoms have been shown to store and concentrate inorganic phosphate (Pi) as amorphous, polyphosphate granules. Subsequent release of these P reserves into the local marine environment as Pi results in biologically induced phosphorite nucleation. Pi storage and release through an intracellular polyphosphate intermediate may also occur in mineralizing oral bacteria. Polyphosphates may be associated with biologically controlled apatite nucleation within vertebrates and invertebrates. Historically, biological apatite nucleation has been attributed to either a biochemical increase in local Pi concentration or matrix-mediated apatite nucleation control. This review proposes a mechanism that integrates both theories. Intracellular and extracellular amorphous granules, rich in both calcium and phosphorus, have been observed in apatite-biomineralizing vertebrates, protists, and atremate brachiopods. These granules may represent stores of calcium-polyphosphate. Not unlike phosphorite nucleation by bacteria and diatoms, polyphosphate depolymerization to Pi would be controlled by phosphatase activity. Enzymatic polyphosphate depolymerization would increase apatite saturation to the level required for mineral nucleation, while matrix proteins would simultaneously control the progression of new biological apatite formation.

Altered tooth morphogenesis after silencing the planar cell polarity core component, Vangl2.

PubMed

Wu, Zhaoming; Epasinghe, Don Jeevanie; He, Jinquan; Li, Liwen; Green, David W; Lee, Min-Jung; Jung, Han-Sung

2016-12-01

Vangl2, one of the core components of the planar cell polarity (PCP) pathway, has an important role in the regulation of morphogenesis in several tissues. Although the expression of Vangl2 has been detected in the developing tooth, its role in tooth morphogenesis is not known. In this study, we show that Vangl2 is expressed in the inner dental epithelium (IDE) and in the secondary enamel knots (SEKs) of bell stage tooth germs. Inhibition of Vangl2 expression by siRNA treatment in in vitro-cultured tooth germs resulted in retarded tooth germ growth with deregulated cell proliferation and apoptosis. After kidney transplantation of Vangl2 siRNA-treated tooth germs, teeth were observed to be small and malformed. We also show that Vangl2 is required to maintain the proper pattern of cell alignment in SEKs, which maybe important for the function of SEKs as signaling centers. These results suggest that Vangl2 plays an important role in the morphogenesis of teeth.

Substantial vertebral body osteophytes protect against severe vertebral fractures in compression

PubMed Central

Aubin, Carl-Éric; Chaumoître, Kathia; Mac-Thiong, Jean-Marc; Ménard, Anne-Laure; Petit, Yvan; Garo, Anaïs; Arnoux, Pierre-Jean

2017-01-01

Recent findings suggest that vertebral osteophytes increase the resistance of the spine to compression. However, the role of vertebral osteophytes on the biomechanical response of the spine under fast dynamic compression, up to failure, is unclear. Seventeen human spine specimens composed of three vertebrae (from T5-T7 to T11-L1) and their surrounding soft tissues were harvested from nine cadavers, aged 77 to 92 years. Specimens were imaged using quantitative computer tomography (QCT) for medical observation, classification of the intervertebral disc degeneration (Thomson grade) and measurement of the vertebral trabecular density (VTD), height and cross-sectional area. Specimens were divided into two groups (with (n = 9) or without (n = 8) substantial vertebral body osteophytes) and compressed axially at a dynamic displacement rate of 1 m/s, up to failure. Normalized force-displacement curves, videos and QCT images allowed characterizing failure parameters (force, displacement and energy at failure) and fracture patterns. Results were analyzed using chi-squared tests for sampling distributions and linear regression for correlations between VTD and failure parameters. Specimens with substantial vertebral body osteophytes present higher stiffness (2.7 times on average) and force at failure (1.8 times on average) than other segments. The presence of osteophytes significantly influences the location, pattern and type of fracture. VTD was a good predictor of the dynamic force and energy at failure for specimens without substantial osteophytes. This study also showed that vertebral body osteophytes provide a protective mechanism to the underlying vertebra against severe compression fractures. PMID:29065144

Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath

PubMed Central

Wang, Shou; Kryvi, Harald; Grotmol, Sindre; Wargelius, Anna; Krossøy, Christel; Epple, Mattias; Neues, Frank; Furmanek, Tomasz; Totland, Geir K

2013-01-01

We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord. PMID:23711083

Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis

PubMed Central

Cavodeassi, Florencia; Ivanovitch, Kenzo; Wilson, Stephen W.

2013-01-01

During forebrain morphogenesis, there is extensive reorganisation of the cells destined to form the eyes, telencephalon and diencephalon. Little is known about the molecular mechanisms that regulate region-specific behaviours and that maintain the coherence of cell populations undergoing specific morphogenetic processes. In this study, we show that the activity of the Eph/Ephrin signalling pathway maintains segregation between the prospective eyes and adjacent regions of the anterior neural plate during the early stages of forebrain morphogenesis in zebrafish. Several Ephrins and Ephs are expressed in complementary domains in the prospective forebrain and combinatorial abrogation of their activity results in incomplete segregation of the eyes and telencephalon and in defective evagination of the optic vesicles. Conversely, expression of exogenous Ephs or Ephrins in regions of the prospective forebrain where they are not usually expressed changes the adhesion properties of the cells, resulting in segregation to the wrong domain without changing their regional fate. The failure of eye morphogenesis in rx3 mutants is accompanied by a loss of complementary expression of Ephs and Ephrins, suggesting that this pathway is activated downstream of the regional fate specification machinery to establish boundaries between domains undergoing different programmes of morphogenesis. PMID:24026122

36th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2015 annual meeting.

PubMed

Gripp, Karen W; Adam, Margaret P; Hudgins, Louanne; Carey, John C

2016-07-01

The 36th Annual David W Smith Workshop on Malformations and Morphogenesis was held on August 14-19, 2015 at the Harbourtowne Conference Center in St. Michaels Maryland. The Workshop, which honors the legacy of David W Smith, brought together over 120 clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. As is the tradition of the meeting, the Workshop highlighted five themes besides mechanisms of morphogenesis: Rasopathies, Eye Malformations, Therapeutics, Prenatal Diagnosis, and Disorders of Sex Development. This Conference Report includes the abstracts presented at the 2015 Workshop. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Canonical TGF-β Signaling Negatively Regulates Neuronal Morphogenesis through TGIF/Smad Complex-Mediated CRMP2 Suppression.

PubMed

Nakashima, Hideyuki; Tsujimura, Keita; Irie, Koichiro; Ishizu, Masataka; Pan, Miao; Kameda, Tomonori; Nakashima, Kinichi

2018-05-16

Functional neuronal connectivity requires proper neuronal morphogenesis and its dysregulation causes neurodevelopmental diseases. Transforming growth factor-β (TGF-β) family cytokines play pivotal roles in development, but little is known about their contribution to morphological development of neurons. Here we show that the Smad-dependent canonical signaling of TGF-β family cytokines negatively regulates neuronal morphogenesis during brain development. Mechanistically, activated Smads form a complex with transcriptional repressor TG-interacting factor (TGIF), and downregulate the expression of a neuronal polarity regulator, collapsin response mediator protein 2. We also demonstrate that TGF-β family signaling inhibits neurite elongation of human induced pluripotent stem cell-derived neurons. Furthermore, the expression of TGF-β receptor 1, Smad4, or TGIF, which have mutations found in patients with neurodevelopmental disorders, disrupted neuronal morphogenesis in both mouse (male and female) and human (female) neurons. Together, these findings suggest that the regulation of neuronal morphogenesis by an evolutionarily conserved function of TGF-β signaling is involved in the pathogenesis of neurodevelopmental diseases. SIGNIFICANCE STATEMENT Canonical transforming growth factor-β (TGF-β) signaling plays a crucial role in multiple organ development, including brain, and mutations in components of the signaling pathway associated with several human developmental disorders. In this study, we found that Smads/TG-interacting factor-dependent canonical TGF-β signaling regulates neuronal morphogenesis through the suppression of collapsin response mediator protein-2 (CRMP2) expression during brain development, and that function of this signaling is evolutionarily conserved in the mammalian brain. Mutations in canonical TGF-β signaling factors identified in patients with neurodevelopmental disorders disrupt the morphological development of neurons. Thus, our

MicroRNA miR-328 Regulates Zonation Morphogenesis by Targeting CD44 Expression

PubMed Central

Wang, Chia-Hui; Lee, Daniel Y.; Deng, Zhaoqun; Jeyapalan, Zina; Lee, Shao-Chen; Kahai, Shireen; Lu, Wei-Yang; Zhang, Yaou; Yang, Burton B.

2008-01-01

Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion. PMID:18560585

MicroRNA miR-328 regulates zonation morphogenesis by targeting CD44 expression.

PubMed

Wang, Chia-Hui; Lee, Daniel Y; Deng, Zhaoqun; Jeyapalan, Zina; Lee, Shao-Chen; Kahai, Shireen; Lu, Wei-Yang; Zhang, Yaou; Yang, Burton B

2008-06-18

Morphogenesis is crucial to initiate physiological development and tumor invasion. Here we show that a microRNA controls zonation morphogenesis by targeting hyaluronan receptor CD44. We have developed a novel system to study microRNA functions by generating constructs expressing pre-miRNAs and mature miRNAs. Using this system, we have demonstrated that expression of miR-328 reduced cell adhesion, aggregation, and migration, and regulated formation of capillary structure. Protein analysis indicated that miR-328 repressed CD44 expression. Activities of luciferase constructs harboring the target site in CD44, but not the one containing mutation, were repressed by miR-328. Zonation morphogenesis appeared in cells transfected by miR-328: miR-328-transfected cells were present on the surface of zonating structures while the control cells stayed in the middle. MiR-328-mediated CD44 actions was validated by anti-CD44 antibody, hyaluronidase, CD44 siRNA, and CD44 expression constructs. In vivo experiments showed that CD44-silencing cells appeared as layers on the surfaces of nodules or zonating structures. Immuno-histochemistry also exhibited CD44-negative cells on the surface layers of normal rat livers and the internal zones of Portal veins. Our results demonstrate that miR-328 targets CD44, which is essential in regulating zonation morphogenesis: silencing of CD44 expression is essential in sealing the zonation structures to facilitate their extension and to inhibit complex expansion.

The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons.

PubMed

Braasch, Ingo; Gehrke, Andrew R; Smith, Jeramiah J; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M; Campbell, Michael S; Barrell, Daniel; Martin, Kyle J; Mulley, John F; Ravi, Vydianathan; Lee, Alison P; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E G; Sun, Yi; Hertel, Jana; Beam, Michael J; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H; Litman, Gary W; Litman, Ronda T; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F; Wang, Han; Taylor, John S; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M J; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T; Venkatesh, Byrappa; Holland, Peter W H; Guiguen, Yann; Bobe, Julien; Shubin, Neil H; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H

2016-04-01

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before teleost genome duplication (TGD). The slowly evolving gar genome has conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization and development (mediated, for example, by Hox, ParaHox and microRNA genes). Numerous conserved noncoding elements (CNEs; often cis regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles for such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses showed that the sums of expression domains and expression levels for duplicated teleost genes often approximate the patterns and levels of expression for gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes and the function of human regulatory sequences.

Efficacy on the risk of vertebral fracture with administration of once-weekly 17.5 mg risedronate in Japanese patients of established osteoporosis with prevalent vertebral fractures: a 156-week longitudinal observational study in daily practice.

PubMed

Soen, Satoshi; Umemura, Takashi; Ando, Tsuyoshi; Kamisaki, Toshiaki; Nishikawa, Masahiko; Muraoka, Ryoichi; Ikeda, Yoshinori; Takeda, Kyoko; Osawa, Mitsuharu; Nakamura, Toshitaka

2017-07-01

Currently, the only available evidence for the efficacy of once-weekly 17.5 mg risedronate in preventing vertebral fractures was obtained in a 48-week study in Japan. We performed a 156-week prospective, longitudinal, observational study to determine the efficacy of the 17.5 mg risedronate in preventing vertebral fractures. We included Japanese patients with established osteoporosis who were older than 50 years and had radiographically confirmed vertebral fractures. The primary endpoint was the incidence of vertebral fractures every 24 weeks, with the final interval spanning 36 weeks. We also calculated the change in bone mineral density of the lumbar spine (L 2-4 BMD) and urinary N-telopeptide of type I collagen (u-NTX), and assessed the incidence of adverse drug reactions and the drug adherence rate. Data from 241 patients were available for analysis of vertebral fracture prevention. The incidence rate of vertebral fractures decreased in a time-dependent manner (P = 0.0006; Poisson regression analysis). The risk ratio (fracture incidence per 100 person-years in the final 36 weeks versus that in the first 24 weeks) was 0.21 (95 % confidence interval 0.08-0.55). Compared to baseline values, L 2-4 BMD increased by 6.41 % at 156 weeks, while u-NTX decreased by 36 % at 24 weeks and was maintained thereafter (P < 0.0001). The incidence rate of adverse drug reactions was 9.18 %. Drug adherence rates assessed every 4 weeks were over 90 %. Our results indicate that 156 weeks of treatment with once-weekly 17.5 mg risedronate effectively reduced the risk of vertebral fracture in Japanese patients with established osteoporosis older than 50 years.

Direct activation of chordoblasts by retinoic acid is required for segmented centra mineralization during zebrafish spine development.

PubMed

Pogoda, Hans-Martin; Riedl-Quinkertz, Iris; Löhr, Heiko; Waxman, Joshua S; Dale, Rodney M; Topczewski, Jacek; Schulte-Merker, Stefan; Hammerschmidt, Matthias

2018-05-08

Zebrafish mutants with increased retinoic acid (RA) signaling due to the loss of the RA-inactivating enzyme Cyp26b1 develop a hyper-mineralized spine with gradually fusing vertebral body precursors (centra). However, the underlying cellular mechanisms remain incompletely understood. Here, we show that cells of the notochord epithelium named chordoblasts are sensitive to RA signaling. Chordoblasts are uniformly distributed along the anteroposterior axis and initially generate the continuous collagenous notochord sheath. However, subsequently and iteratively, subsets of these cells undergo further RA-dependent differentiation steps, acquire a stellate-like shape, downregulate expression of the collagen gene col2a1a , switch on cyp26b1 expression and trigger metameric sheath mineralization. This mineralization fails to appear upon chordoblast-specific cell ablation or RA signal transduction blockade. Together, our data reveal that, despite their different developmental origins, the activities and regulation of chordoblasts are very similar to those of osteoblasts, including their RA-induced transition from osteoid-producing cells to osteoid-mineralizing ones. Furthermore, our data point to a requirement for locally controlled RA activity within the chordoblast layer in order to generate the segmented vertebral column. © 2018. Published by The Company of Biologists Ltd.

The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures.

PubMed

Ma, Jinhui; Siminoski, Kerry; Alos, Nathalie; Halton, Jacqueline; Ho, Josephine; Lentle, Brian; Matzinger, MaryAnn; Shenouda, Nazih; Atkinson, Stephanie; Barr, Ronald; Cabral, David A; Couch, Robert; Cummings, Elizabeth A; Fernandez, Conrad V; Grant, Ronald M; Rodd, Celia; Sbrocchi, Anne Marie; Scharke, Maya; Rauch, Frank; Ward, Leanne M

2015-03-01

Our objectives were to assess the magnitude of the disparity in lumbar spine bone mineral density (LSBMD) Z-scores generated by different reference databases and to evaluate whether the relationship between LSBMD Z-scores and vertebral fractures (VF) varies by choice of database. Children with leukemia underwent LSBMD by cross-calibrated dual-energy x-ray absorptiometry, with Z-scores generated according to Hologic and Lunar databases. VF were assessed by the Genant method on spine radiographs. Logistic regression was used to assess the association between fractures and LSBMD Z-scores. Net reclassification improvement and area under the receiver operating characteristic curve were calculated to assess the predictive accuracy of LSBMD Z-scores for VF. For the 186 children from 0 to 18 years of age, 6 different age ranges were studied. The Z-scores generated for the 0 to 18 group were highly correlated (r ≥ 0.90), but the proportion of children with LSBMD Z-scores ≤-2.0 among those with VF varied substantially (from 38-66%). Odds ratios (OR) for the association between LSBMD Z-score and VF were similar regardless of database (OR = 1.92, 95% confidence interval 1.44, 2.56 to OR = 2.70, 95% confidence interval 1.70, 4.28). Area under the receiver operating characteristic curve and net reclassification improvement ranged from 0.71 to 0.75 and -0.15 to 0.07, respectively. Although the use of a LSBMD Z-score threshold as part of the definition of osteoporosis in a child with VF does not appear valid, the study of relationships between BMD and VF is valid regardless of the BMD database that is used.

Primary extracranial vertebral artery aneurysms.

PubMed

Morasch, Mark D; Phade, Sachin V; Naughton, Peter; Garcia-Toca, Manuel; Escobar, Guillermo; Berguer, Ramon

2013-05-01

Extracranial vertebral artery aneurysms are uncommon and are usually associated with trauma or dissection. Primary cervical vertebral aneurysms are even rarer and are not well described. The presentation and natural history are unknown and operative management can be difficult. Accessing aneurysms at the skull base can be difficult and, because the frail arteries are often afflicted with connective tissue abnormalities, direct repair can be particularly challenging. We describe the presentation and surgical management of patients with primary extracranial vertebral artery aneurysms. In this study we performed a retrospective, multi-institutional review of patients with primary aneurysms within the extracranial vertebral artery. Between January 2000 and January 2011, 7 patients, aged 12-56 years, were noted to have 9 primary extracranial vertebral artery aneurysms. All had underlying connective tissue or another hereditary disorder, including Ehler-Danlos syndrome (n=3), Marfan's disease (n=2), neurofibromatosis (n=1), and an unspecified connective tissue abnormality (n=1). Eight of 9 aneurysms were managed operatively, including an attempted bypass that ultimately required vertebral ligation; the contralateral aneurysm on this patient has not been treated. Open interventions included vertebral bypass with vein, external carotid autograft, and vertebral transposition to the internal carotid artery. Special techniques were used for handling the anastomoses in patients with Ehler-Danlos syndrome. Although endovascular exclusion was not performed in isolation, 2 hybrid procedures were performed. There were no instances of perioperative stroke or death. Primary extracranial vertebral artery aneurysms are rare and occur in patients with hereditary disorders. Operative intervention is warranted in symptomatic patients. Exclusion and reconstruction may be performed with open and hybrid techniques with low morbidity and mortality. Copyright © 2013 Elsevier Inc. All rights

Geranylgeranyl Diphosphate Synthase Modulates Fetal Lung Branching Morphogenesis Possibly through Controlling K-Ras Prenylation.

PubMed

Jia, Wen-Jun; Jiang, Shan; Tang, Qiao-Li; Shen, Di; Xue, Bin; Ning, Wen; Li, Chao-Jun

2016-06-01

G proteins play essential roles in regulating fetal lung development, and any defects in their expression or function (eg, activation or posttranslational modification) can lead to lung developmental malformation. Geranylgeranyl diphosphate synthase (GGPPS) can modulate protein prenylation that is required for protein membrane-anchoring and activation. Here, we report that GGPPS regulates fetal lung branching morphogenesis possibly through controlling K-Ras prenylation during fetal lung development. GGPPS was continuously expressed in lung epithelium throughout whole fetal lung development. Specific deletion of geranylgeranyl diphosphate synthase 1 (Ggps1) in lung epithelium during fetal lung development resulted in neonatal respiratory distress syndrome-like disease. The knockout mice died at postnatal day 1 of respiratory failure, and the lungs showed compensatory pneumonectasis, pulmonary atelectasis, and hyaline membranes. Subsequently, we proved that lung malformations in Ggps1-deficient mice resulted from the failure of fetal lung branching morphogenesis. Further investigation revealed Ggps1 deletion blocked K-Ras geranylgeranylation and extracellular signal-related kinase 1 or 2/mitogen-activated protein kinase signaling, which in turn disturbed fibroblast growth factor 10 regulation on fetal lung branching morphogenesis. Collectively, our data suggest that GGPPS is essential for maintaining fetal lung branching morphogenesis, which is possibly through regulating K-Ras prenylation. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Histology and affinity of anaspids, and the early evolution of the vertebrate dermal skeleton

PubMed Central

Keating, Joseph N.; Donoghue, Philip C. J.

2016-01-01

The assembly of the gnathostome bodyplan constitutes a formative episode in vertebrate evolutionary history, an interval in which the mineralized skeleton and its canonical suite of cell and tissue types originated. Fossil jawless fishes, assigned to the gnathostome stem-lineage, provide an unparalleled insight into the origin and evolution of the skeleton, hindered only by uncertainty over the phylogenetic position and evolutionary significance of key clades. Chief among these are the jawless anaspids, whose skeletal composition, a rich source of phylogenetic information, is poorly characterized. Here we survey the histology of representatives spanning anaspid diversity and infer their generalized skeletal architecture. The anaspid dermal skeleton is composed of odontodes comprising spheritic dentine and enameloid, overlying a basal layer of acellular parallel fibre bone containing an extensive shallow canal network. A recoded and revised phylogenetic analysis using equal and implied weights parsimony resolves anaspids as monophyletic, nested among stem-gnathostomes. Our results suggest the anaspid dermal skeleton is a degenerate derivative of a histologically more complex ancestral vertebrate skeleton, rather than reflecting primitive simplicity. Hypotheses that anaspids are ancestral skeletonizing lampreys, or a derived lineage of jawless vertebrates with paired fins, are rejected. PMID:26962140

Stronger back muscles reduce the incidence of vertebral fractures: a prospective 10 year follow-up of postmenopausal women.

PubMed

Sinaki, M; Itoi, E; Wahner, H W; Wollan, P; Gelzcer, R; Mullan, B P; Collins, D A; Hodgson, S F

2002-06-01

The long-term protective effect of stronger back muscles on the spine was determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years after they had completed a 2 year randomized, controlled trial. Twenty-seven subjects had performed progressive, resistive back-strengthening exercises for 2 years and 23 had served as controls. Bone mineral density, spine radiographs, back extensor strength, biochemical marker values, and level of physical activity were obtained for all subjects at baseline, 2 years, and 10 years. Mean back extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline, 66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10 years (8 years after cessation of the prescribed exercises). Mean BES in the control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10 years. The difference between the two groups was still statistically significant at 10 year follow-up (p = 0.001). The difference in bone mineral density, which was not significant between the two groups at baseline and 2 year follow-up, was significant at 10 year follow-up (p = 0.0004). The incidence of vertebral compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE group (chi-square test, p = 0.0290). The relative risk for compression fracture was 2.7 times greater in the C group than in the BE group. To our knowledge, this is the first study reported in the literature demonstrating the long-term effect of strong back muscles on the reduction of vertebral fractures in estrogen-deficient women.

Ngn3+ endocrine progenitor cells control the fate and morphogenesis of pancreatic ductal epithelium

PubMed Central

Magenheim, Judith; Klein, Allon M.; Stanger, Ben Z.; Ashery-Padan, Ruth; Sosa-Pineda, Beatriz; Gu, Guoqiang; Dor, Yuval

2013-01-01

Summary During pancreas development, endocrine and exocrine cells arise from a common multipotent progenitor pool. How these cell fate decisions are coordinated with tissue morphogenesis is poorly understood. Here we have examined ductal morphology, endocrine progenitor cell fate and Notch signaling in Ngn3−/− mice, which do not produce islet cells. Ngn3 deficiency results in reduced branching and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter activation throughout the ductal epithelium and reduced Notch signaling. Conversely, forced generation of surplus endocrine progenitor cells causes reduced duct caliber and an excessive number of tip cells. Thus, endocrine progenitor cells normally provide a feedback signal to adjacent multipotent ductal progenitor cells that activates Notch signaling, inhibits further endocrine differentiation and promotes proper morphogenesis. These results uncover a novel layer of regulation coordinating pancreas morphogenesis and endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta-cells from stem cells. PMID:21888903

Vertebral fractures assessed with dual-energy X-ray absorptiometry in patients with Addison's disease on glucocorticoid and mineralocorticoid replacement therapy.

PubMed

Camozzi, Valentina; Betterle, Corrado; Frigo, Anna Chiara; Zaccariotto, Veronica; Zaninotto, Martina; De Caneva, Erica; Lucato, Paola; Gomiero, Walter; Garelli, Silvia; Sabbadin, Chiara; Salvà, Monica; Costa, Miriam Dalla; Boscaro, Marco; Luisetto, Giovanni

2018-02-01

to assess bone damage and metabolic abnormalities in patients with Addison's disease given replacement doses of glucocorticoids and mineralocorticoids. A total of 87 patients and 81 age-matched and sex-matched healthy controls were studied. The following parameters were measured: urinary cortisol, serum calcium, phosphorus, creatinine, 24-h urinary calcium excretion, bone alkaline phosphatase, parathyroid hormone, serum CrossLaps, 25 hydroxyvitamin D, and 1,25 dihydroxyvitamin D. Clear vertebral images were obtained with dual-energy X-ray absorptiometry in 61 Addison's disease patients and 47 controls and assessed using Genant's classification. Nineteen Addison's disease patients (31.1%) had at least one morphometric vertebral fracture, as opposed to six controls (12.8%, odds ratio 3.09, 95% confidence interval 1.12-8.52). There were no significant differences in bone mineral density parameters at any site between patients and controls. In Addison's disease patients, there was a positive correlation between urinary cortisol and urinary calcium excretion. Patients with fractures had a longer history of disease than those without fractures. Patients taking fludrocortisone had a higher bone mineral density than untreated patients at all sites except the lumbar spine. Addison's disease patients have more fragile bones irrespective of any decrease in bone mineral density. Supra-physiological doses of glucocorticoids and longer-standing disease (with a consequently higher glucocorticoid intake) might be the main causes behind patients' increased bone fragility. Associated mineralocorticoid treatment seems to have a protective effect on bone mineral density.

Tissue-specific activities of the Fat1 cadherin cooperate to control neuromuscular morphogenesis

PubMed Central

2018-01-01

Muscle morphogenesis is tightly coupled with that of motor neurons (MNs). Both MNs and muscle progenitors simultaneously explore the surrounding tissues while exchanging reciprocal signals to tune their behaviors. We previously identified the Fat1 cadherin as a regulator of muscle morphogenesis and showed that it is required in the myogenic lineage to control the polarity of progenitor migration. To expand our knowledge on how Fat1 exerts its tissue-morphogenesis regulator activity, we dissected its functions by tissue-specific genetic ablation. An emblematic example of muscle under such morphogenetic control is the cutaneous maximus (CM) muscle, a flat subcutaneous muscle in which progenitor migration is physically separated from the process of myogenic differentiation but tightly associated with elongating axons of its partner MNs. Here, we show that constitutive Fat1 disruption interferes with expansion and differentiation of the CM muscle, with its motor innervation and with specification of its associated MN pool. Fat1 is expressed in muscle progenitors, in associated mesenchymal cells, and in MN subsets, including the CM-innervating pool. We identify mesenchyme-derived connective tissue (CT) as a cell type in which Fat1 activity is required for the non–cell-autonomous control of CM muscle progenitor spreading, myogenic differentiation, motor innervation, and for motor pool specification. In parallel, Fat1 is required in MNs to promote their axonal growth and specification, indirectly influencing muscle progenitor progression. These results illustrate how Fat1 coordinates the coupling of muscular and neuronal morphogenesis by playing distinct but complementary actions in several cell types. PMID:29768404

Mineralization of the vertebral bodies in Atlantic salmon (Salmo salar L.) is initiated segmentally in the form of hydroxyapatite crystal accretions in the notochord sheath.

PubMed

Wang, Shou; Kryvi, Harald; Grotmol, Sindre; Wargelius, Anna; Krossøy, Christel; Epple, Mattias; Neues, Frank; Furmanek, Tomasz; Totland, Geir K

2013-08-01

We performed a sequential morphological and molecular biological study of the development of the vertebral bodies in Atlantic salmon (Salmo salar L.). Mineralization starts in separate bony elements which fuse to form complete segmental rings within the notochord sheath. The nucleation and growth of hydroxyapatite crystals in both the lamellar type II collagen matrix of the notochord sheath and the lamellar type I collagen matrix derived from the sclerotome, were highly similar. In both matrices the hydroxyapatite crystals nucleate and accrete on the surface of the collagen fibrils rather than inside the fibrils, a process that may be controlled by a template imposed by the collagen fibrils. Apatite crystal growth starts with the formation of small plate-like structures, about 5 nm thick, that gradually grow and aggregate to form extensive multi-branched crystal arborizations, resembling dendritic growth. The hydroxyapatite crystals are always oriented parallel to the long axis of the collagen fibrils, and the lamellar collagen matrices provide oriented support for crystal growth. We demonstrate here for the first time by means of synchroton radiation based on X-ray diffraction that the chordacentra contain hydroxyapatite. We employed quantitative real-time PCR to study the expression of key signalling molecule transcripts expressed in the cellular core of the notochord. The results indicate that the notochord not only produces and maintains the notochord sheath but also expresses factors known to regulate skeletogenesis: sonic hedgehog (shh), indian hedgehog homolog b (ihhb), parathyroid hormone 1 receptor (pth1r) and transforming growth factor beta 1 (tgfb1). In conclusion, our study provides evidence for the process of vertebral body development in teleost fishes, which is initially orchestrated by the notochord. © 2013 Anatomical Society.

Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study

PubMed Central

Liang, Cheng-Loong; Wang, Hao-Kwan; Syu, Fei-Kai; Wang, Kuo-Wei; Lu, Kang; Liliang, Po-Chou

2015-01-01

Purpose Postvertebral augmentation vertebral compression fractures are common; repeated vertebral augmentation is usually performed for prompt pain relief. This study aimed to evaluate the incidence and risk factors of repeat vertebral augmentation. Methods We performed a retrospective, nationwide, population-based longitudinal observation study, using the National Health Insurance Research Database (NHIRD) of Taiwan. All patients who received vertebral augmentation for vertebral compression fractures were evaluated. The collected data included patient characteristics (demographics, comorbidities, and medication exposure) and repeat vertebral augmentation. Kaplan–Meier and stratified Cox proportional hazard regressions were performed for analyses. Results The overall incidence of repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients with the following characteristics were at greater risk for repeat vertebral augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10–2.36), advanced age (AOR=1.60; 95% CI: 1.32–2.08), diabetes mellitus (AOR=4.31; 95% CI: 4.05–5.88), cerebrovascular disease (AOR=4.09; 95% CI: 3.44–5.76), dementia (AOR=1.97; 95% CI: 1.69–2.33), blindness or low vision (AOR=3.72; 95% CI: 2.32–3.95), hypertension (AOR=2.58; 95% CI: 2.35–3.47), and hyperlipidemia (AOR=2.09; 95% CI: 1.67–2.22). Patients taking calcium/vitamin D (AOR=2.98; 95% CI: 1.83–3.93), bisphosphonates (AOR=2.11; 95% CI: 1.26–2.61), or calcitonin (AOR=4.59; 95% CI: 3.40–5.77) were less likely to undergo repeat vertebral augmentation; however, those taking steroids (AOR=7.28; 95% CI: 6.32–8.08), acetaminophen (AOR=3.54; 95% CI: 2.75–4.83), or nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR=6.14; 95% CI: 5.08–7.41) were more likely to undergo repeat vertebral augmentation. Conclusion We conclude that the incidence of repeat vertebral augmentation is rather high. An understanding of risk factors predicting repeat

Bone mineral density and vertebral fractures in patients with systemic lupus erythematosus: A systematic review and meta-regression.

PubMed

Mendoza-Pinto, Claudia; Rojas-Villarraga, Adriana; Molano-González, Nicolás; Jiménez-Herrera, Erick A; León-Vázquez, María de la Luz; Montiel-Jarquín, Álvaro; García-Carrasco, Mario; Cervera, Ricard

2018-01-01

Observational studies have indicated a high but heterogeneous prevalence of low bone mineral density (BMD) and vertebral fractures (VF) in patients with systemic lupus erythematosus (SLE). Therefore, the objectives of this systematic review and meta-regression were: 1) to compare BMD between SLE patients and healthy controls and 2) to evaluate the relationship between BMD and glucocorticoid therapy and VF in SLE patients. Articles were identified from electronic databases (PubMed, Embase, VHL, SciELO and the Cochrane Library). Prospective longitudinal and cross-sectional studies were considered for review. We evaluated the quality of the evidence included using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence. In total, 38 articles were identified and analyzed (3442 SLE cases and 6198 controls) in the analysis of BMD (9232 women and 408 men). There were significant differences in mean BMD between SLE patients and controls. BMD mean difference in cases/controls: -0.0566 95% CI (-0.071, -0.0439; p = < 0.0001). When only SLE patients were analyzed, the BMD did not significantly differ between patients who had or had not received glucocorticoid (GCT) therapy. 694 SLE patients were included in the analysis of VF (189 with VF vs. 505 without VF). Patients with VF had lower BMD than patients without VF (BMD mean difference without VF/with VF: 0.033 (95%CI: 0.006-0.060); p-value: 0.0156). Patients with SLE had lower BMD than healthy controls. Moreover, SLE patients with VF had lower BMD than patients without VF. However, our data did not show that GCT therapy had an impact on BMD.

IGF-1 Regulates Vertebral Bone Aging Through Sex-Specific and Time-Dependent Mechanisms.

PubMed

Ashpole, Nicole M; Herron, Jacquelyn C; Mitschelen, Matthew C; Farley, Julie A; Logan, Sreemathi; Yan, Han; Ungvari, Zoltan; Hodges, Erik L; Csiszar, Anna; Ikeno, Yuji; Humphrey, Mary Beth; Sonntag, William E

2016-02-01

suggest the age-related loss of vertebral bone density in females can be reduced by modifying circulating IGF-1 levels early in life. © 2015 American Society for Bone and Mineral Research.

Lower Jump Power Rather Than Muscle Mass Itself is Associated with Vertebral Fracture in Community-Dwelling Elderly Korean Women.

PubMed

Lee, Eun Young; Lee, Su Jin; Kim, Kyoung Min; Seo, Da Hea; Lee, Seung Won; Choi, Han Sol; Kim, Hyeon Chang; Youm, Yoosik; Kim, Chang Oh; Rhee, Yumie

2017-06-01

Sarcopenia is considered to be a risk factor for osteoporotic fracture, which is a major health problem in elderly women. In this study, we aimed to investigate the association of sarcopenia, with regard to muscle mass and function, with prevalent vertebral fracture in community-dwelling elderly women. We recruited 1281 women aged 64 to 87 years from the Korean Urban Rural Elderly cohort study. Muscle mass and function were measured using bioimpedance analysis and jumping mechanography. Skeletal muscle index (SMI) and jump power were used as an indicator of muscle mass and function, respectively. Among the participants, we observed 282 (18.9%) vertebral fractures and 564 (44.0%) osteoporosis. Although age, body mass index, and prevalence of osteoporosis increased as both SMI and jump power decreased, prevalence of vertebral fracture increased only when jump power decreased. In univariate analysis, compared with the highest quartile of jump power, the lowest quartile had a significant odds ratio of 2.80 (95% CI 1.79-4.36) for vertebral fracture. This association between jump power and vertebral fracture remained significant, with an odds ratio of 3.04 (95% CI 1.77-5.23), even after adjusting for other risk factors including age, bone mineral density, previous fracture, and cognitive function. In contrast, there was no association between SMI and vertebral fracture. Based on our results, low jump power, but not SMI, is associated with vertebral fracture in community-dwelling elderly Korean women. This finding suggests that jump power may have a more important role than muscle mass itself for osteoporotic fracture.

E- and P-cadherin expression during murine hair follicle morphogenesis and cycling.

PubMed

Müller-Röver, S; Tokura, Y; Welker, P; Furukawa, F; Wakita, H; Takigawa, M; Paus, R

1999-08-01

The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.

Notochord Morphogenesis in Mice: Current Understanding & Open Questions

PubMed Central

Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

2016-01-01

The notochord is the structure which defines chordates. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Interestingly, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. PMID:26845388

The spotted gar genome illuminates vertebrate evolution and facilitates human-to-teleost comparisons

PubMed Central

Braasch, Ingo; Gehrke, Andrew R.; Smith, Jeramiah J.; Kawasaki, Kazuhiko; Manousaki, Tereza; Pasquier, Jeremy; Amores, Angel; Desvignes, Thomas; Batzel, Peter; Catchen, Julian; Berlin, Aaron M.; Campbell, Michael S.; Barrell, Daniel; Martin, Kyle J.; Mulley, John F.; Ravi, Vydianathan; Lee, Alison P.; Nakamura, Tetsuya; Chalopin, Domitille; Fan, Shaohua; Wcisel, Dustin; Cañestro, Cristian; Sydes, Jason; Beaudry, Felix E. G.; Sun, Yi; Hertel, Jana; Beam, Michael J.; Fasold, Mario; Ishiyama, Mikio; Johnson, Jeremy; Kehr, Steffi; Lara, Marcia; Letaw, John H.; Litman, Gary W.; Litman, Ronda T.; Mikami, Masato; Ota, Tatsuya; Saha, Nil Ratan; Williams, Louise; Stadler, Peter F.; Wang, Han; Taylor, John S.; Fontenot, Quenton; Ferrara, Allyse; Searle, Stephen M. J.; Aken, Bronwen; Yandell, Mark; Schneider, Igor; Yoder, Jeffrey A.; Volff, Jean-Nicolas; Meyer, Axel; Amemiya, Chris T.; Venkatesh, Byrappa; Holland, Peter W. H.; Guiguen, Yann; Bobe, Julien; Shubin, Neil H.; Di Palma, Federica; Alföldi, Jessica; Lindblad-Toh, Kerstin; Postlethwait, John H.

2016-01-01

To connect human biology to fish biomedical models, we sequenced the genome of spotted gar (Lepisosteus oculatus), whose lineage diverged from teleosts before the teleost genome duplication (TGD). The slowly evolving gar genome conserved in content and size many entire chromosomes from bony vertebrate ancestors. Gar bridges teleosts to tetrapods by illuminating the evolution of immunity, mineralization, and development (e.g., Hox, ParaHox, and miRNA genes). Numerous conserved non-coding elements (CNEs, often cis-regulatory) undetectable in direct human-teleost comparisons become apparent using gar: functional studies uncovered conserved roles of such cryptic CNEs, facilitating annotation of sequences identified in human genome-wide association studies. Transcriptomic analyses revealed that the sum of expression domains and levels from duplicated teleost genes often approximate patterns and levels of gar genes, consistent with subfunctionalization. The gar genome provides a resource for understanding evolution after genome duplication, the origin of vertebrate genomes, and the function of human regulatory sequences. PMID:26950095

Association of osteolytic lesions, bone mineral loss and trabecular sclerosis with prevalent vertebral fractures in patients with multiple myeloma.

PubMed

Borggrefe, J; Giravent, S; Campbell, G; Thomsen, F; Chang, D; Franke, M; Günther, A; Heller, M; Wulff, A

2015-11-01

In patients with multiple myeloma (MM), computed tomography is widely used for staging and to detect fractures. Detecting patients at severe fracture risk is of utmost importance. However the criteria for impaired stability of vertebral bodies are not yet clearly defined. We investigated the performance of parameters that can be detected by the radiologist for discrimination of patients with and without fractures. We analyzed 128 whole body low-dose CT of MM patients. In all scans a QCT calibration phantom was integrated into the positioning mat (Image Analysis Phantom(®)). A QCT-software (Structural Insight) performed the volumetric bone mineral density (vBMD) measurements. Description of fracture risk was provided from the clinical radiological report. Suspected progressive disease (PD) was reported by the referring clinicians. Two radiologists that were blinded to study outcome reported on the following parameters based on predefined criteria: reduced radiodensity in the massa lateralis of the os sacrum (RDS), trabecular thickening and sclerosis of three or more vertebrae (TTS), extraosseous MM manifestations (EOM), visible small osteolytic lesions up to a length of 8mm (SO) and osteolytic lesions larger than 8mm (LO). Prevalent vertebral fractures (PVF) were defined by Genant criteria. Age-adjusted standardized odds ratios (sOR) per standard deviation change were derived from logistic regression analysis and area under the curve (AUC) from receiver operating characteristics (ROC) analyses were calculated. ROC curves were compared using the DeLong method. 45% of the 128 patients showed PVF (29 of 75 men, 24 of 53 women). Patients with PVF were not significantly older than patients without fractures (64.6 ± 9.2 vs. 63.3 ± 12.3 years: mean ± SD, p=0.5). The prevalence of each parameter did not differ significantly by sex. Significant fracture discrimination for age adjusted single models was provided by the parameters vBMD (OR 3.5 [1.4-8.8], AUC=0.64 ± 0

Rapid onset aggressive vertebral haemangioma.

PubMed

Cheung, Nicholas K; Doorenbosch, Xenia; Christie, John G

2011-03-01

Vertebral haemangiomas are generally benign asymptomatic vascular tumours seen commonly in the adult population. Presentations in paediatric populations are extremely rare, which can result in rapid onset of neurological symptoms. We present a highly unusual case of an aggressive paediatric vertebral haemangioma causing significant cord compression. A 13-year-old boy presented with only 2 weeks duration of progressive gait disturbance, truncal ataxia and loss of bladder control. Magnetic resonance imaging (MRI) of the spine revealed a large vascular epidural mass extending between T6 and T8 vertebral bodies. Associated displacement and compression of the spinal cord was present. A highly vascular bony lesion was found during surgery. Histopathology identified this tumour to be a vertebral haemangioma. We present an extremely unusual acute presentation of a paediatric vertebral haemangioma. This study highlights the need for early diagnosis, MRI for investigation and urgent surgical management. © Springer-Verlag 2011

Dynamics of vascular branching morphogenesis: The effect of blood and tissue flow

NASA Astrophysics Data System (ADS)

Nguyen, Thi-Hanh; Eichmann, Anne; Le Noble, Ferdinand; Fleury, Vincent

2006-06-01

Vascularization of embryonic organs or tumors starts from a primitive lattice of capillaries. Upon perfusion, this lattice is remodeled into branched arteries and veins. Adaptation to mechanical forces is implied to play a major role in arterial patterning. However, numerical simulations of vessel adaptation to haemodynamics has so far failed to predict any realistic vascular pattern. We present in this article a theoretical modeling of vascular development in the yolk sac based on three features of vascular morphogenesis: the disconnection of side branches from main branches, the reconnection of dangling sprouts (“dead ends”), and the plastic extension of interstitial tissue, which we have observed in vascular morphogenesis. We show that the effect of Poiseuille flow in the vessels can be modeled by aggregation of random walkers. Solid tissue expansion can be modeled by a Poiseuille (parabolic) deformation, hence by deformation under hits of random walkers. Incorporation of these features, which are of a mechanical nature, leads to realistic modeling of vessels, with important biological consequences. The model also predicts the outcome of simple mechanical actions, such as clamping of vessels or deformation of tissue by the presence of obstacles. This study offers an explanation for flow-driven control of vascular branching morphogenesis.

Tissue architecture, cell traction, deformable scaffolds, and the forces that shape the embryo during morphogenesis.

NASA Astrophysics Data System (ADS)

Davidson, Lance

2005-03-01

Morphogenesis is the process of constucting form and shape. Morphogenesis during early development of the embryo involves orchestrated movements of cells and tissues. These morphogenetic movements establish the body plan and organs of the early embryo. The rates and trajectories of these movements depend on three physical features of the early embryo: 1) the forces generated by cells, 2) the mechanical properties of the tissues, and 3) the architecture of the tissues. These three mechanical features of the embryo are some of the earliest phenotypic features generated by the genome. We are taking an interdisciplinary approach combining biophysical, cell biological, and classical embryological techniques to understand the mechanics of morphogenesis. Using nanoNewton-sensitive force transducers we can apply forces and measure time dependent elastic modulii of tissue fragments 100 micrometers across. Using traction-force microscopy we can measure forces generated by cells on their environment. We use drugs and chimeric proteins to investigate the localization and function of molecular complexes responsible for force generation and the modulus. We use microsurgery to take-apart and construct novel tissues to investigate the role of geometry and architecture in the mechanics of morphogenesis. Together with simulation techniques these quantitative approaches will provide us with a practical nuts-and-bolts understanding of how the genome encodes the shapes and forms of life.

Extra-embryonic tissue spreading directs early embryo morphogenesis in killifish

PubMed Central

Reig, Germán; Cerda, Mauricio; Sepúlveda, Néstor; Flores, Daniela; Castañeda, Victor; Tada, Masazumi; Härtel, Steffen; Concha, Miguel L.

2017-01-01

The spreading of mesenchymal-like cell layers is critical for embryo morphogenesis and tissue repair, yet we know little of this process in vivo. Here we take advantage of unique developmental features of the non-conventional annual killifish embryo to study the principles underlying tissue spreading in a simple cellular environment, devoid of patterning signals and major morphogenetic cell movements. Using in vivo experimentation and physical modelling we reveal that the extra-embryonic epithelial enveloping cell layer, thought mainly to provide protection to the embryo, directs cell migration and the spreading of embryonic tissue during early development. This function relies on the ability of embryonic cells to couple their autonomous random motility to non-autonomous signals arising from the expansion of the extra-embryonic epithelium, mediated by cell membrane adhesion and tension. Thus, we present a mechanism of extra-embryonic control of embryo morphogenesis that couples the mechanical properties of adjacent tissues in the early killifish embryo. PMID:28580937

Cement Leakage in Percutaneous Vertebral Augmentation for Osteoporotic Vertebral Compression Fractures: Analysis of Risk Factors.

PubMed

Xie, Weixing; Jin, Daxiang; Ma, Hui; Ding, Jinyong; Xu, Jixi; Zhang, Shuncong; Liang, De

2016-05-01

The risk factors for cement leakage were retrospectively reviewed in 192 patients who underwent percutaneous vertebral augmentation (PVA). To discuss the factors related to the cement leakage in PVA procedure for the treatment of osteoporotic vertebral compression fractures. PVA is widely applied for the treatment of osteoporotic vertebral fractures. Cement leakage is a major complication of this procedure. The risk factors for cement leakage were controversial. A retrospective review of 192 patients who underwent PVA was conducted. The following data were recorded: age, sex, bone density, number of fractured vertebrae before surgery, number of treated vertebrae, severity of the treated vertebrae, operative approach, volume of injected bone cement, preoperative vertebral compression ratio, preoperative local kyphosis angle, intraosseous clefts, preoperative vertebral cortical bone defect, and ratio and type of cement leakage. To study the correlation between each factor and cement leakage ratio, bivariate regression analysis was employed to perform univariate analysis, whereas multivariate linear regression analysis was employed to perform multivariate analysis. The study included 192 patients (282 treated vertebrae), and cement leakage occurred in 100 vertebrae (35.46%). The vertebrae with preoperative cortical bone defects generally exhibited higher cement leakage ratio, and the leakage is typically type C. Vertebrae with intact cortical bones before the procedure tend to experience type S leakage. Univariate analysis showed that patient age, bone density, number of fractured vertebrae before surgery, and vertebral cortical bone were associated with cement leakage ratio (P<0.05). Multivariate analysis showed that the main factors influencing bone cement leakage are bone density and vertebral cortical bone defect, with standardized partial regression coefficients of -0.085 and 0.144, respectively. High bone density and vertebral cortical bone defect are

The lamprey: a jawless vertebrate model system for examining origin of the neural crest and other vertebrate traits.

PubMed

Green, Stephen A; Bronner, Marianne E

2014-01-01

Lampreys are a group of jawless fishes that serve as an important point of comparison for studies of vertebrate evolution. Lampreys and hagfishes are agnathan fishes, the cyclostomes, which sit at a crucial phylogenetic position as the only living sister group of the jawed vertebrates. Comparisons between cyclostomes and jawed vertebrates can help identify shared derived (i.e. synapomorphic) traits that might have been inherited from ancestral early vertebrates, if unlikely to have arisen convergently by chance. One example of a uniquely vertebrate trait is the neural crest, an embryonic tissue that produces many cell types crucial to vertebrate features, such as the craniofacial skeleton, pigmentation of the skin, and much of the peripheral nervous system (Gans and Northcutt, 1983). Invertebrate chordates arguably lack unambiguous neural crest homologs, yet have cells with some similarities, making comparisons with lampreys and jawed vertebrates essential for inferring characteristics of development in early vertebrates, and how they may have evolved from nonvertebrate chordates. Here we review recent research on cyclostome neural crest development, including research on lamprey gene regulatory networks and differentiated neural crest fates. Copyright © 2014 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis.

PubMed

Edens, Brittany M; Yan, Jianhua; Miller, Nimrod; Deng, Han-Xiang; Siddique, Teepu; Ma, Yongchao C

2017-05-02

The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways.

Nanoforms: a new type of protein-associated mineralization

NASA Astrophysics Data System (ADS)

Vali, Hojatollah; McKee, Marc D.; Çiftçioglu, Neva; Sears, S. Kelly; Plows, Fiona L.; Chevet, Eric; Ghiabi, Pegah; Plavsic, Marc; Kajander, E. Olavi; Zare, Richard N.

2001-01-01

Controversy surrounds the interpretation of various nano-phenomena as being living organisms. Incubation of fetal bovine serum under standard cell culture conditions results in the formation of free entities in solution, here referred to as nanoforms. These nanoforms, when examined by transmission electron microscopy, have a distinct ovoid morphology ranging in size from tens to hundreds of nanometers. They are composed of hydroxyapatite and proteins and constitute a novel form of protein-associated mineralization. No detectable cell structure resembling bacteria is apparent. However, immunodetection of the proteins associated with the nanoforms, by two specific monoclonal antibodies, suggests a possible biogenic origin. The significance of nanoforms for the recognition of biological activity in ancient geological systems is discussed. The mode of mineralization in nanoforms is also compared to matrix-mediated calcification in vertebrates.

Determinants of prevalent vertebral fractures and progressive bone loss in long-term hemodialysis patients.

PubMed

Mares, Jan; Ohlidalova, Kristina; Opatrna, Sylvie; Ferda, Jiri

2009-01-01

Skeletal fractures are common in hemodialysis (HD) patients. However, consensus regarding technique and site of bone examination has not been reached in HD patients. Seventy-two patients (44% females) aged 65 (1.4) years, treated with HD for 43 (4.6) months were examined with quantitative computed tomography and 53 of them re-examined after 1 year. Bone mineral density (BMD) of lumbar spine was established separately for cortical and trabecular bone, prevalent vertebral fractures were determined. Data are given as mean (standard error). At least one vertebral fracture was discovered in 15 (21%) patients. In a logistic regression model, fractures were best predicted by cortical BMD: OR 0.96 (CI 0.94, 0.99), p < 0.005. With a multiple regression analysis, time on dialysis was found to be independently correlated to cortical BMD (R = 0.35, p < 0.005). On follow-up, a decrease of BMD was detected, which occurred only in the cortical region and was significantly greater in females than in males: -7% (1.7) versus 1.2% (1.9), p < 0.005. A time-dependent loss of vertebral cortical bone occurs in HD patients, especially in females. This decrement may impose an increased risk of fractures on long-term dialysis patients.

Transcriptional regulation of neuronal polarity and morphogenesis in the mammalian brain

PubMed Central

de la Torre-Ubieta, Luis; Bonni, Azad

2012-01-01

The highly specialized morphology of a neuron, typically consisting of a long axon and multiple branching dendrites, lies at the core of the principle of dynamic polarization, whereby information flows from dendrites toward the soma and to the axon. For more than a century neuroscientists have been fascinated by how shape is important for neuronal function and how neurons acquire their characteristic morphology. During the past decade, substantial progress has been made in our understanding of the molecular underpinnings of neuronal polarity and morphogenesis. In these studies, transcription factors have emerged as key players governing multiple aspects of neuronal morphogenesis from neuronal polarization and migration to axon growth and pathfinding to dendrite growth and branching to synaptogenesis. In this review, we will highlight the role of transcription factors in shaping neuronal morphology with emphasis on recent literature in mammalian systems. PMID:21982366

Reverse engineering the mechanical and molecular pathways in stem cell morphogenesis.

PubMed

Lu, Kai; Gordon, Richard; Cao, Tong

2015-03-01

The formation of relevant biological structures poses a challenge for regenerative medicine. During embryogenesis, embryonic cells differentiate into somatic tissues and undergo morphogenesis to produce three-dimensional organs. Using stem cells, we can recapitulate this process and create biological constructs for therapeutic transplantation. However, imperfect imitation of nature sometimes results in in vitro artifacts that fail to recapitulate the function of native organs. It has been hypothesized that developing cells may self-organize into tissue-specific structures given a correct in vitro environment. This proposition is supported by the generation of neo-organoids from stem cells. We suggest that morphogenesis may be reverse engineered to uncover its interacting mechanical pathway and molecular circuitry. By harnessing the latent architecture of stem cells, novel tissue-engineering strategies may be conceptualized for generating self-organizing transplants. Copyright © 2013 John Wiley & Sons, Ltd.

Iodine-enhanced micro-CT imaging: methodological refinements for the study of the soft-tissue anatomy of post-embryonic vertebrates.

PubMed

Gignac, Paul M; Kley, Nathan J

2014-05-01

The now widespread use of non-destructive X-ray computed tomography (CT) and micro-CT (µCT) has greatly augmented our ability to comprehensively detail and quantify the internal hard-tissue anatomy of vertebrates. However, the utility of X-ray imaging for gaining similar insights into vertebrate soft-tissue anatomy has yet to be fully realized due to the naturally low X-ray absorption of non-mineralized tissues. In this study, we show how a wide diversity of soft-tissue structures within the vertebrate head-including muscles, glands, fat deposits, perichondria, dural venous sinuses, white and gray matter of the brain, as well as cranial nerves and associated ganglia-can be rapidly visualized in their natural relationships with extraordinary levels of detail using iodine-enhanced (i-e) µCT imaging. To date, Lugol's iodine solution (I2 KI) has been used as a contrast agent for µCT imaging of small invertebrates, vertebrate embryos, and certain isolated parts of larger, post-embryonic vertebrates. These previous studies have all yielded promising results, but visualization of soft tissues in smaller invertebrate and embryonic vertebrate specimens has generally been more complete than that for larger, post-embryonic vertebrates. Our research builds on these previous studies by using high-energy µCT together with more highly concentrated I2 KI solutions and longer staining times to optimize the imaging and differentiation of soft tissues within the heads of post-embryonic archosaurs (Alligator mississippiensis and Dromaius novaehollandiae). We systematically quantify the intensities of tissue staining, demonstrate the range of anatomical structures that can be visualized, and generate a partial three-dimensional reconstruction of alligator cephalic soft-tissue anatomy. © 2014 Wiley Periodicals, Inc.

Testing Skills in Vertebrates

ERIC Educational Resources Information Center

Funk, Mildred Sears; Tosto, Pat

2007-01-01

In this article, the authors present a project that gives students examples of basic skills that many vertebrate species develop as they grow and function in their ecosystem. These activities involve information gathering about surroundings, learning how to use objects, and tracking and searching skills. Different vertebrate species may acquire…

Newt tail regeneration: a model for gravity-dependent morphogenesis and clues to the molecular mechanisms involved.

NASA Astrophysics Data System (ADS)

Radugina, Elena A.; Almeida, Eduardo; Grigoryan, Eleonora

Gravity alterations are widely recognized to influence living systems. They may cause temporary or permanent effects on physiology and development at different levels, from gene expression to morphogenesis. However, the molecular mechanisms underlying these effects are often unclear, and adequate model systems to study them are required. To address this problem we developed a new experimental model of how gravity affects morphogenesis during tail regeneration in the newt Pleurodeles waltl. The effects of increased gravity on newt tail morphogenesis were first documented in two joint Russian-US NASA spaceflight experiments in the Russian Foton-M2 (2005) and Foton-M3 (2007) missions. In these experiments the shape of newt tail regenerate was found to depend on the gravity level, being dorso-ventrally symmetrical in microgravity and in neutrally-buoyant aquarium controls, versus hook-like and bent downward in 1g controls. These 1g controls were conducted in spaceflight habitats using a water-saturated PVA sponge mat. These results were reproducible in multiple spaceflight, and ground laboratory studies, both in the US at NASA ARC and in Russia at IDB RAS, and were characterized in detail using morphometry and histology approaches. The role of hypergravity in shaping morphogenesis was confirmed at NASA ARC with an experiment in the ISS Testbed 8-foot diameter centrifuge operating at 2g. Animals that experienced two-week centrifugation (the period of time used in the Foton flights) developed the same hook-like regenerates as 1g controls, and morphometric analysis revealed no significant difference between 1g and 2g groups, however both were significantly different from aquarium controls. We hypothesize that exposure to 1g or 2g during tail morphogenesis constitutes excessive loading for newts that are adapted to microgravity-like conditions in their aquatic habitat. Because Heat Shock Proteins (HSPs) are stress-induced molecules that respond to a broad variety of

Insights into the diagenetic environment of fossil marine vertebrates of the Pisco Formation (late Miocene, Peru) from mineralogical and Sr-isotope data

NASA Astrophysics Data System (ADS)

Gioncada, A.; Petrini, R.; Bosio, G.; Gariboldi, K.; Collareta, A.; Malinverno, E.; Bonaccorsi, E.; Di Celma, C.; Pasero, M.; Urbina, M.; Bianucci, G.

2018-01-01

The late Miocene Pisco Formation of Peru is an outstanding example of richness and high-quality preservation of fossil marine vertebrates. In order to reconstruct the fossilization path, we present new textural, mineralogical and Sr-isotope data of diagenetic minerals formed in correspondence of fossil specimens such as marine vertebrates and mollusks. These fossil specimens were found at Cerro los Quesos, in the Ica Desert, within the diatomaceous strata of the Pisco Formation. Dolomite, gypsum, anhydrite and Mn minerals are the main phases found, while the calcium carbonate originally forming the mollusk valves is replaced by gypsum. An early formation of dolomite and of Mn minerals, triggered by the modifications of the geochemical environment due to organic matter degradation, is suggested by the textural relationships and is confirmed by the Sr isotopic ratio of dolomite, which agrees with that of seawater at the time of sedimentation. Instead, gypsum Sr isotopic ratios indicate a pre-Miocene seawater-derived brine circulating within the sedimentary sequence as a source for Sr. Oxidation of diagenetic sulfide causing a lowering of the pH of porewater is proposed as an explanation for Ca-carbonate dissolution. The diagenetic chemical environment was, nevertheless, favorable to bone preservation.

Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: A Systematic Review

PubMed Central

Pron, Gaylene; Holubowich, Corinne; Kaulback, Kellee

2016-01-01

Background Cancers that metastasize to the spine and primary cancers such as multiple myeloma can result in vertebral compression fractures or instability. Conservative strategies, including bed rest, bracing, and analgesic use, can be ineffective, resulting in continued pain and progressive functional disability limiting mobility and self-care. Surgery is not usually an option for cancer patients in advanced disease states because of their poor medical health or functional status and limited life expectancy. The objectives of this review were to evaluate the effectiveness and safety of percutaneous image-guided vertebral augmentation techniques, vertebroplasty and kyphoplasty, for palliation of cancer-related vertebral compression fractures. Methods We performed a systematic literature search for studies on vertebral augmentation of cancer-related vertebral compression fractures published from January 1, 2000, to October 2014; abstracts were screened by a single reviewer. For those studies meeting the eligibility criteria, full-text articles were obtained. Owing to the heterogeneity of the clinical reports, we performed a narrative synthesis based on an analytical framework constructed for the type of cancer-related vertebral fractures and the diversity of the vertebral augmentation interventions. Results The evidence review identified 3,391 citations, of which 111 clinical reports (4,235 patients) evaluated the effectiveness of vertebroplasty (78 reports, 2,545 patients) or kyphoplasty (33 reports, 1,690 patients) for patients with mixed primary spinal metastatic cancers, multiple myeloma, or hemangiomas. Overall the mean pain intensity scores often reported within 48 hours of vertebral augmentation (kyphoplasty or vertebroplasty), were significantly reduced. Analgesic use, although variably reported, usually involved parallel decreases, particularly in opioids, and mean pain-related disability scores were also significantly improved. In a randomized controlled

Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: A Systematic Review.

PubMed

2016-01-01

Cancers that metastasize to the spine and primary cancers such as multiple myeloma can result in vertebral compression fractures or instability. Conservative strategies, including bed rest, bracing, and analgesic use, can be ineffective, resulting in continued pain and progressive functional disability limiting mobility and self-care. Surgery is not usually an option for cancer patients in advanced disease states because of their poor medical health or functional status and limited life expectancy. The objectives of this review were to evaluate the effectiveness and safety of percutaneous image-guided vertebral augmentation techniques, vertebroplasty and kyphoplasty, for palliation of cancer-related vertebral compression fractures. We performed a systematic literature search for studies on vertebral augmentation of cancer-related vertebral compression fractures published from January 1, 2000, to October 2014; abstracts were screened by a single reviewer. For those studies meeting the eligibility criteria, full-text articles were obtained. Owing to the heterogeneity of the clinical reports, we performed a narrative synthesis based on an analytical framework constructed for the type of cancer-related vertebral fractures and the diversity of the vertebral augmentation interventions. The evidence review identified 3,391 citations, of which 111 clinical reports (4,235 patients) evaluated the effectiveness of vertebroplasty (78 reports, 2,545 patients) or kyphoplasty (33 reports, 1,690 patients) for patients with mixed primary spinal metastatic cancers, multiple myeloma, or hemangiomas. Overall the mean pain intensity scores often reported within 48 hours of vertebral augmentation (kyphoplasty or vertebroplasty), were significantly reduced. Analgesic use, although variably reported, usually involved parallel decreases, particularly in opioids, and mean pain-related disability scores were also significantly improved. In a randomized controlled trial comparing kyphoplasty

A model for neurite growth and neuronal morphogenesis.

PubMed

Li, G H; Qin, C D

1996-02-01

A model is presented for tensile regulation of neuritic growth. It is proposed that the neurite tension can be determined by Hooke's law and determines the growth rate of neurites. The growth of a neurite is defined as the change in its unstretched length. Neuritic growth rate is assumed to increase in proportion to tension magnitude over a certain threshold [Dennerll et al., J. Cell Biol. 107: 665-674 (1988)]. The movement of branch nodes also contributes to the neuronal morphogenesis. It is supposed that the rate of a branch-node displacement is in proportion to the resultant neuritic tension exerted on this node. To deal with the growth-cone movement, it is further supposed that the environment exerts a traction force on the growth cone and the rate of growth-cone displacement is determined by the vector sum of the neuritic tension and the traction force. A group of differential equations are used to describe the model. The key point of the model is that the traction force and the neuritic tension are in opposition to generate a temporal contrast-enhancing mechanism. Results of a simulation study suggest that the model can explain some phenomena related to neuronal morphogenesis.

The Bio-Logic and machinery of plant morphogenesis.

PubMed

Niklas, Karl J

2003-04-01

Morphogenesis (the development of organic form) requires signal-trafficking and cross-talking across all levels of organization to coordinate the operation of metabolic and genomic networked systems. Many biologists are currently converging on the pictorial conventions of computer scientists to render biological signaling as logic circuits supervising the operation of one or more signal-activated metabolic or gene networks. This approach can redact and simplify complex morphogenetic phenomena and allows for their aggregation into diagrams of larger, more "global" networked systems. This conceptualization is discussed in terms of how logic circuits and signal-activated subsystems work, and it is illustrated for examples of increasingly more complex morphogenetic phenomena, e.g., auxin-mediated cell expansion, entry into the mitotic cell cycle phases, and polar/lateral intercellular auxin transport. For each of these phenomena, a posited circuit/subsystem diagram draws rapid attention to missing components, either in the logic circuit or in the subsystem it supervises. These components must be identified experimentally if each of these basic phenomena is to be fully understood. Importantly, the power of the circuit/subsystem approach to modeling developmental phenomena resides not in its pictorial appeal but in the mathematical tools that are sufficiently strong to reveal and quantify the synergistics of networked systems and thus foster a better understanding of morphogenesis.

Vertebral body innervation: Implications for pain.

PubMed

Buonocore, Michelangelo; Aloisi, Anna Maria; Barbieri, Massimo; Gatti, Anna Maria; Bonezzi, Cesare

2010-03-01

Vertebral fractures often cause intractable pain. To define the involvement of vertebral body innervation in pain, we collected specimens from male and female patients during percutaneous kyphoplasty, a procedure used for reconstruction of the vertebral body. Specimens were taken from 31 patients (9 men and 22 women) suffering high-intensity pain before surgery. In total, 1,876 histological preparations were obtained and analysed. Immunohistochemical techniques were used to locate the nerves in the specimens. The nerve fibres were labelled by indirect immunofluorescence with the primary antibody directed against Protein Gene Product 9.5 (PGP 9.5), a pan-neuronal marker; another primary antibody directed against type IV collagen (Col IV) was used to identify vessels and to determine their relationship with vertebral nerve fibres. The mean percentage of samples in which it was possible to identify nerve fibres was 35% in men and 29% in women. The percentages varied depending on the spinal level considered and the sex of the subject, nerve fibres being mostly present around vessels (95%). In conclusion, there is scarce innervation of the vertebral bodies, with a clear prevalence of fibres located around vessels. It seems unlikely that this pattern of vertebral body innervation is involved in vertebral pain or in pain relief following kyphoplasty.

Collagen type XI alpha1 may be involved in the structural plasticity of the vertebral column in Atlantic salmon (Salmo salar L.).

PubMed

Wargelius, A; Fjelldal, P G; Nordgarden, U; Grini, A; Krossøy, C; Grotmol, S; Totland, G K; Hansen, T

2010-04-01

Atlantic salmon (Salmo salar L.) vertebral bone displays plasticity in structure, osteoid secretion and mineralization in response to photoperiod. Other properties of the vertebral bone, such as mineral content and mechanical strength, are also associated with common malformations in farmed Atlantic salmon. The biological mechanisms that underlie these changes in bone physiology are unknown, and in order to elucidate which factors might be involved in this process, microarray assays were performed on vertebral bone of Atlantic salmon reared under natural or continuous light. Eight genes were upregulated in response to continuous light treatment, whereas only one of them was upregulated in a duplicate experiment. The transcriptionally regulated gene was predicted to code for collagen type XI alpha1, a protein known to be involved in controlling the diameter of fibrillar collagens in mammals. Furthermore, the gene was highly expressed in the vertebrae, where spatial expression was found in trabecular and compact bone osteoblasts and in the chordoblasts of the notochordal sheath. When we measured the expression level of the gene in the tissue compartments of the vertebrae, the collagen turned out to be 150 and 25 times more highly expressed in the notochord and compact bone respectively, relative to the expression in the trabecular bone. Gene expression was induced in response to continuous light, and reduced in compressed vertebrae. The downregulation in compressed vertebrae was due to reduced expression in the compact bone, while expression in the trabecular bone and the notochord was unaffected. These data support the hypothesis that this gene codes for a presumptive collagen type XI alpha1, which may be involved in the regulatory pathway leading to structural adaptation of the vertebral architecture.

A minimally invasive vertebral hemangioma.

PubMed

Van den Broeck, S; Mailleux, P; Joris, J P

2010-01-01

We describe a very unusual vertebral hemangioma presenting with a mixture of aggressive-like pattern (epidural extension, T1 hyposignal) and quiescent, inactive lesion (fatty infiltration), in association with a spiculated calcified epidural component.This paper emphasizes that CT and/or MR findings are accurate enough to make formal assessment of vertebral hemangioma, preventing patient's anguish and moreover unnecessary treatment. Furthermore this attractive case proposes a poorly known characteristic of vertebral hemangioma which is usually encountered and described only in skull hemangiomas.

Globally threatened vertebrates on islands with invasive species

PubMed Central

Spatz, Dena R.; Zilliacus, Kelly M.; Holmes, Nick D.; Butchart, Stuart H. M.; Genovesi, Piero; Ceballos, Gerardo; Tershy, Bernie R.; Croll, Donald A.

2017-01-01

Global biodiversity loss is disproportionately rapid on islands, where invasive species are a major driver of extinctions. To inform conservation planning aimed at preventing extinctions, we identify the distribution and biogeographic patterns of highly threatened terrestrial vertebrates (classified by the International Union for Conservation of Nature) and invasive vertebrates on ~465,000 islands worldwide by conducting a comprehensive literature review and interviews with more than 500 experts. We found that 1189 highly threatened vertebrate species (319 amphibians, 282 reptiles, 296 birds, and 292 mammals) breed on 1288 islands. These taxa represent only 5% of Earth’s terrestrial vertebrates and 41% of all highly threatened terrestrial vertebrates, which occur in <1% of islands worldwide. Information about invasive vertebrates was available for 1030 islands (80% of islands with highly threatened vertebrates). Invasive vertebrates were absent from 24% of these islands, where biosecurity to prevent invasions is a critical management tool. On the 76% of islands where invasive vertebrates were present, management could benefit 39% of Earth’s highly threatened vertebrates. Invasive mammals occurred in 97% of these islands, with Rattus sp. as the most common invasive vertebrate (78%; 609 islands). Our results provide an important baseline for identifying islands for invasive species eradication and other island conservation actions that reduce biodiversity loss. PMID:29075662

Globally threatened vertebrates on islands with invasive species.

PubMed

Spatz, Dena R; Zilliacus, Kelly M; Holmes, Nick D; Butchart, Stuart H M; Genovesi, Piero; Ceballos, Gerardo; Tershy, Bernie R; Croll, Donald A

2017-10-01

Global biodiversity loss is disproportionately rapid on islands, where invasive species are a major driver of extinctions. To inform conservation planning aimed at preventing extinctions, we identify the distribution and biogeographic patterns of highly threatened terrestrial vertebrates (classified by the International Union for Conservation of Nature) and invasive vertebrates on ~465,000 islands worldwide by conducting a comprehensive literature review and interviews with more than 500 experts. We found that 1189 highly threatened vertebrate species (319 amphibians, 282 reptiles, 296 birds, and 292 mammals) breed on 1288 islands. These taxa represent only 5% of Earth's terrestrial vertebrates and 41% of all highly threatened terrestrial vertebrates, which occur in <1% of islands worldwide. Information about invasive vertebrates was available for 1030 islands (80% of islands with highly threatened vertebrates). Invasive vertebrates were absent from 24% of these islands, where biosecurity to prevent invasions is a critical management tool. On the 76% of islands where invasive vertebrates were present, management could benefit 39% of Earth's highly threatened vertebrates. Invasive mammals occurred in 97% of these islands, with Rattus sp. as the most common invasive vertebrate (78%; 609 islands). Our results provide an important baseline for identifying islands for invasive species eradication and other island conservation actions that reduce biodiversity loss.

Hormonally active phytochemicals and vertebrate evolution.

PubMed

Lambert, Max R; Edwards, Thea M

2017-06-01

Living plants produce a diversity of chemicals that share structural and functional properties with vertebrate hormones. Wildlife species interact with these chemicals either through consumption of plant materials or aquatic exposure. Accumulating evidence shows that exposure to these hormonally active phytochemicals (HAPs) often has consequences for behavior, physiology, and fecundity. These fitness effects suggest there is potential for an evolutionary response by vertebrates to HAPs. Here, we explore the toxicological HAP-vertebrate relationship in an evolutionary framework and discuss the potential for vertebrates to adapt to or even co-opt the effects of plant-derived chemicals that influence fitness. We lay out several hypotheses about HAPs and provide a path forward to test whether plant-derived chemicals influence vertebrate reproduction and evolution. Studies of phytochemicals with direct impacts on vertebrate reproduction provide an obvious and compelling system for studying evolutionary toxicology. Furthermore, an understanding of whether animal populations evolve in response to HAPs could provide insightful context for the study of rapid evolution and how animals cope with chemical agents in the environment.

To grow or not to grow: Hair morphogenesis and human genetic hair disorders

PubMed Central

Duverger, Olivier; Morasso, Maria I.

2014-01-01

Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. PMID:24361867

To grow or not to grow: hair morphogenesis and human genetic hair disorders.

PubMed

Duverger, Olivier; Morasso, Maria I

2014-01-01

Mouse models have greatly helped in elucidating the molecular mechanisms involved in hair formation and regeneration. Recent publications have reviewed the genes involved in mouse hair development based on the phenotype of transgenic, knockout and mutant animal models. While much of this information has been instrumental in determining molecular aspects of human hair development and cycling, mice exhibit a specific pattern of hair morphogenesis and hair distribution throughout the body that cannot be directly correlated to human hair. In this mini-review, we discuss specific aspects of human hair follicle development and present an up-to-date summary of human genetic disorders associated with abnormalities in hair follicle morphogenesis, structure or regeneration. Published by Elsevier Ltd.

Physics of Bacterial Morphogenesis

PubMed Central

Sun, Sean X.; Jiang, Hongyuan

2011-01-01

Summary: Bacterial cells utilize three-dimensional (3D) protein assemblies to perform important cellular functions such as growth, division, chemoreception, and motility. These assemblies are composed of mechanoproteins that can mechanically deform and exert force. Sometimes, small-nucleotide hydrolysis is coupled to mechanical deformations. In this review, we describe the general principle for an understanding of the coupling of mechanics with chemistry in mechanochemical systems. We apply this principle to understand bacterial cell shape and morphogenesis and how mechanical forces can influence peptidoglycan cell wall growth. We review a model that can potentially reconcile the growth dynamics of the cell wall with the role of cytoskeletal proteins such as MreB and crescentin. We also review the application of mechanochemical principles to understand the assembly and constriction of the FtsZ ring. A number of potential mechanisms are proposed, and important questions are discussed. PMID:22126993

Stenting for symptomatic vertebral artery stenosis: The Vertebral Artery Ischaemia Stenting Trial.

PubMed

Markus, Hugh S; Larsson, Susanna C; Kuker, Wilhelm; Schulz, Ursula G; Ford, Ian; Rothwell, Peter M; Clifton, Andrew

2017-09-19

To compare in the Vertebral Artery Ischaemia Stenting Trial (VIST) the risks and benefits of vertebral angioplasty and stenting with best medical treatment (BMT) alone for symptomatic vertebral artery stenosis. VIST was a prospective, randomized, open-blinded endpoint clinical trial performed in 14 hospitals in the United Kingdom. Participants with symptomatic vertebral stenosis ≥50% were randomly assigned (1:1) to vertebral angioplasty/stenting plus BMT or to BMT alone with randomization stratified by site of stenosis (extracranial vs intracranial). Because of slow recruitment and cessation of funding, recruitment was stopped after 182 participants. Follow-up was a minimum of ≥1 year for each participant. Three patients did not contribute any follow-up data and were excluded, leaving 91 patients in the stent group and 88 in the medical group. Mean follow-up was 3.5 (interquartile range 2.1-4.7) years. Of 61 patients who were stented, stenosis was extracranial in 48 (78.7%) and intracranial in 13 (21.3%). No periprocedural complications occurred with extracranial stenting; 2 strokes occurred during intracranial stenting. The primary endpoint of fatal or nonfatal stroke occurred in 5 patients in the stent group vs 12 in the medical group (hazard ratio 0.40, 95% confidence interval 0.14-1.13, p = 0.08), with an absolute risk reduction of 25 strokes per 1,000 person-years. The hazard ratio for stroke or TIA was 0.50 ( p = 0.05). Stenting in extracranial stenosis appears safe with low complication rates. Large phase 3 trials are required to determine whether stenting reduces stroke risk. ISRCTN95212240. This study provides Class I evidence that for patients with symptomatic vertebral stenosis, angioplasty with stenting does not reduce the risk of stroke. However, the study lacked the precision to exclude a benefit from stenting. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

DRhoGEF2 and Diaphanous Regulate Contractile Force during Segmental Groove Morphogenesis in the Drosophila Embryo

PubMed Central

Mulinari, Shai; Barmchi, Mojgan Padash

2008-01-01

Morphogenesis of the Drosophila embryo is associated with dynamic rearrangement of the actin cytoskeleton mediated by small GTPases of the Rho family. These GTPases act as molecular switches that are activated by guanine nucleotide exchange factors. One of these factors, DRhoGEF2, plays an important role in the constriction of actin filaments during pole cell formation, blastoderm cellularization, and invagination of the germ layers. Here, we show that DRhoGEF2 is equally important during morphogenesis of segmental grooves, which become apparent as tissue infoldings during mid-embryogenesis. Examination of DRhoGEF2-mutant embryos indicates a role for DRhoGEF2 in the control of cell shape changes during segmental groove morphogenesis. Overexpression of DRhoGEF2 in the ectoderm recruits myosin II to the cell cortex and induces cell contraction. At groove regression, DRhoGEF2 is enriched in cells posterior to the groove that undergo apical constriction, indicating that groove regression is an active process. We further show that the Formin Diaphanous is required for groove formation and strengthens cell junctions in the epidermis. Morphological analysis suggests that Dia regulates cell shape in a way distinct from DRhoGEF2. We propose that DRhoGEF2 acts through Rho1 to regulate acto-myosin constriction but not Diaphanous-mediated F-actin nucleation during segmental groove morphogenesis. PMID:18287521

Prevalence of osteoporosis, vertebral fractures and hypovitaminosis D in postmenopausal women living in a rural environment.

PubMed

Gómez-de-Tejada Romero, María-Jesús; Navarro Rodríguez, María-del-Carmen; Saavedra Santana, Pedro; Quesada Gómez, José-Manuel; Jódar Gimeno, Esteban; Sosa Henríquez, Manuel

2014-03-01

First, to study the difference between two groups of postmenopausal women living in different population centres (rural vs urban) in the prevalence of osteoporosis, fragility fractures and factors which may influence them: hypovitaminosis D, bone mineral density, coexistence of other diseases which predispose to their appearance; secondly, to observe the influence of low socioeconomic status, categorised as poverty. 1229 postmenopausal women were studied, of whom 390 (31.7%), were living in rural areas and 839 (68.3%), in urban areas. Data regarding risk factors related to osteoporosis were obtained, and, among other biochemical measures, 25 hydroxyvitamin D and parathyroid hormone were determined. Bone densitometry was carried out in the lumbar spine and proximal femur, as well as lateral X-rays of the dorsal and lumbar spine. The women who lived in rural areas were older, shorter, heavier and had a higher body mass index than those from urban areas. Among the women from rural areas there was a higher prevalence of poverty, and higher levels of obesity, arterial hypertension and diabetes mellitus were observed, as well as a higher prevalence of densitometric osteoporosis. The rural women had lower values of bone mineral density in the lumbar spine and a higher prevalence of vertebral fractures and hypovitaminosis D. The variables which were associated independently with living in rural areas were poverty, obesity, vertebral fractures, BMD in the lumbar spine and levels of 25 hydroxyvitamin D. In our study, postmenopausal women who live in rural populations have more poverty, lower values of vitamin D, lower BMD in the lumbar spine and a higher prevalence of vertebral fractures and of osteoporosis. The higher prevalence of obesity, arterial hypertension and diabetes mellitus observed in these women may be adjuvant factors, all fostered by their socioeconomic state of poverty. Copyright © 2014. Published by Elsevier Ireland Ltd.

Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis.

PubMed

Gansner, John M; Madsen, Erik C; Mecham, Robert P; Gitlin, Jonathan D

2008-10-01

Recent studies demonstrate that lysyl oxidase cuproenzymes are critical for zebrafish notochord formation, but the molecular mechanisms of copper-dependent notochord morphogenesis are incompletely understood. We, therefore, conducted a forward genetic screen for zebrafish mutants that exhibit notochord sensitivity to lysyl oxidase inhibition, yielding a mutant with defects in notochord and vascular morphogenesis, puff daddygw1 (pfdgw1). Meiotic mapping and cloning reveal that the pfdgw1 phenotype results from disruption of the gene encoding the extracellular matrix protein fibrillin-2, and the spatiotemporal expression of fibrillin-2 is consistent with the pfdgw1 phenotype. Furthermore, each aspect of the pfdgw1 phenotype is recapitulated by morpholino knockdown of fibrillin-2. Taken together, the data reveal a genetic interaction between fibrillin-2 and the lysyl oxidases in notochord formation and demonstrate the importance of fibrillin-2 in specific early developmental processes in zebrafish. Copyright (c) 2008 Wiley-Liss, Inc.

A novel ALS-associated variant in UBQLN4 regulates motor axon morphogenesis

PubMed Central

Edens, Brittany M; Yan, Jianhua; Miller, Nimrod; Deng, Han-Xiang; Siddique, Teepu; Ma, Yongchao C

2017-01-01

The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in UBQLN4 that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated UBQLN4 variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a UBQLN4 substrate. Inhibition of beta-catenin function rescues the UBQLN4 variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways. DOI: http://dx.doi.org/10.7554/eLife.25453.001 PMID:28463112

Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: An Economic Analysis.

PubMed

2016-01-01

Untreated vertebral compression fractures can have serious clinical consequences and impose a considerable impact on patients' quality of life and on caregivers. Since non-surgical management of these fractures has limited effectiveness, vertebral augmentation procedures are gaining acceptance in clinical practice for pain control and fracture stabilization. The objective of this analysis was to determine the cost-effectiveness and budgetary impact of kyphoplasty or vertebroplasty compared with non-surgical management for the treatment of vertebral compression fractures in patients with cancer. We performed a systematic review of health economic studies to identify relevant studies that compare the cost-effectiveness of kyphoplasty or vertebroplasty with non-surgical management for the treatment of vertebral compression fractures in adults with cancer. We also performed a primary cost-effectiveness analysis to assess the clinical benefits and costs of kyphoplasty or vertebroplasty compared with non-surgical management in the same population. We developed a Markov model to forecast benefits and harms of treatments, and corresponding quality-adjusted life years and costs. Clinical data and utility data were derived from published sources, while costing data were derived using Ontario administrative sources. We performed sensitivity analyses to examine the robustness of the results. In addition, a 1-year budget impact analysis was performed using data from Ontario administrative sources. Two scenarios were explored: (a) an increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario, maintaining the current proportion of kyphoplasty versus vertebroplasty; and (b) no increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario but an increase in the proportion of kyphoplasties versus vertebroplasties. The base case considered each of kyphoplasty and vertebroplasty

Vertebral Augmentation Involving Vertebroplasty or Kyphoplasty for Cancer-Related Vertebral Compression Fractures: An Economic Analysis

PubMed Central

2016-01-01

Background Untreated vertebral compression fractures can have serious clinical consequences and impose a considerable impact on patients' quality of life and on caregivers. Since non-surgical management of these fractures has limited effectiveness, vertebral augmentation procedures are gaining acceptance in clinical practice for pain control and fracture stabilization. The objective of this analysis was to determine the cost-effectiveness and budgetary impact of kyphoplasty or vertebroplasty compared with non-surgical management for the treatment of vertebral compression fractures in patients with cancer. Methods We performed a systematic review of health economic studies to identify relevant studies that compare the cost-effectiveness of kyphoplasty or vertebroplasty with non-surgical management for the treatment of vertebral compression fractures in adults with cancer. We also performed a primary cost-effectiveness analysis to assess the clinical benefits and costs of kyphoplasty or vertebroplasty compared with non-surgical management in the same population. We developed a Markov model to forecast benefits and harms of treatments, and corresponding quality-adjusted life years and costs. Clinical data and utility data were derived from published sources, while costing data were derived using Ontario administrative sources. We performed sensitivity analyses to examine the robustness of the results. In addition, a 1-year budget impact analysis was performed using data from Ontario administrative sources. Two scenarios were explored: (a) an increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario, maintaining the current proportion of kyphoplasty versus vertebroplasty; and (b) no increase in the total number of vertebral augmentation procedures performed among patients with cancer in Ontario but an increase in the proportion of kyphoplasties versus vertebroplasties. Results The base case considered each of

Prospective Single-Site Experience with Radiofrequency-Targeted Vertebral Augmentation for Osteoporotic Vertebral Compression Fracture

PubMed Central

Moser, Franklin G.; Maya, Marcel M.; Blaszkiewicz, Laura; Scicli, Andrea; Miller, Larry E.; Block, Jon E.

2013-01-01

Vertebral augmentation procedures are widely used to treat osteoporotic vertebral compression fractures (VCFs). We report our initial experience with radiofrequency-targeted vertebral augmentation (RF-TVA) in 20 patients aged 50 to 90 years with single-level, symptomatic osteoporotic VCF between T10 and L5, back pain severity > 4 on a 0 to 10 scale, Oswestry Disability Index ≥ 21%, 20% to 90% vertebral height loss compared to adjacent vertebral body, and fracture age < 6 months. After treatment, patients were followed through hospital discharge and returned for visits after 1 week, 1 month, and 3 months. Back pain severity improved 66% (P < 0.001), from 7.9 (95% CI: 7.1 to 8.6) at pretreatment to 2.7 (95% CI: 1.5 to 4.0) at 3 months. Back function improved 46% (P < 0.001), from 74 (95% CI: 69% to 79%) at pretreatment to 40 (95% CI: 33% to 47%) at 3 months. The percentage of patients regularly consuming pain medication was 70% at pretreatment and only 21% at 3 months. No adverse events related to the device or procedure were reported. RF-TVA reduces back pain severity, improves back function, and reduces pain medication requirements with no observed complications in patients with osteoporotic VCF. PMID:24228187

Zic1 and Zic4 regulate zebrafish roof plate specification and hindbrain ventricle morphogenesis

PubMed Central

Elsen, Gina E.; Choi, Louis; Millen, Kathleen; Grinblat, Yevgenya; Prince, Victoria E.

2008-01-01

During development, the lumen of the neural tube develops into a system of brain cavities or ventricles, which play important roles in normal CNS function. We have established that the formation of the hindbrain (4th) ventricle in zebrafish is dependent upon the pleiotropic functions of the genes implicated in human Dandy Walker Malformation, Zic1 and Zic4. Using morpholino knockdown we show that zebrafish Zic1 and Zic4 are required for normal morphogenesis of the 4th ventricle. In Zic1 and/or Zic4 morphants the ventricle does not open properly, but remains completely or partially fused from the level of rhombomere (r) 2 towards the posterior. In the absence of Zic function early hindbrain regionalization and neural crest development remain unaffected, but dorsal hindbrain progenitor cell proliferation is significantly reduced. Importantly, we find that Zic1 and Zic4 are required for development of the dorsal roof plate. In Zic morphants expression of roof plate markers, including lmx1b.1 and lmx1b.2, is disrupted. We further demonstrate that zebrafish Lmx1b function is required for both hindbrain roof plate development and 4th ventricle morphogenesis, confirming that roof plate formation is a critical component of ventricle development. Finally, we show that dorsal rhombomere boundary signaling centers depend on Zic1 and Zic4 function and on roof plate signals, and provide evidence that these boundary signals are also required for ventricle morphogenesis. In summary, we conclude that Zic1 and Zic4 control zebrafish 4th ventricle morphogenesis by regulating multiple mechanisms including cell proliferation and fate specification in the dorsal hindbrain. PMID:18191121

Why do chimpanzees hunt? Considering the benefits and costs of acquiring and consuming vertebrate versus invertebrate prey.

PubMed

Tennie, Claudio; O'Malley, Robert C; Gilby, Ian C

2014-06-01

Understanding the benefits and costs of acquiring and consuming different forms of animal matter by primates is critical for identifying the selective pressures responsible for increased meat consumption in the hominin lineage. Chimpanzees (Pan troglodytes) are unusual among primates in the amount of vertebrate prey they consume. Still, surprisingly little is known about the nutritional benefits of eating meat for this species. In order to understand why chimpanzees eat vertebrates, it is critical to consider the relative benefits and costs of other types of faunivory - including invertebrates. Although we lack specific nutritional data on the flesh and organs of chimpanzee prey, the macronutrient profiles of insects and wild vertebrate meat are generally comparable on a gram-to-gram basis. There are currently very few data on the micronutrient (vitamin and mineral) content of meat consumed by chimpanzees. With few exceptions, the advantages of hunting vertebrate prey include year-round availability, rapid acquisition of larger packages and reduced handling/processing time (once prey are encountered or detected). The disadvantages of hunting vertebrate prey include high potential acquisition costs per unit time (energy expenditure and risk of injury) and greater contest competition with conspecifics. Acquiring an equivalent mass of invertebrates (to match even a small scrap of meat) is possible, but typically takes more time. Furthermore, in contrast to vertebrate prey, some insect resources are effectively available only at certain times of the year. Here we identify the critical data needed to test our hypothesis that meat scraps may have a higher (or at least comparable) net benefit:cost ratio than insect prey. This would support the 'meat scrap' hypothesis as an explanation for why chimpanzees hunt in groups even when doing so does not maximize an individual's energetic gain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Calcium isotope fractionation between soft and mineralized tissues as a monitor of calcium use in vertebrates.

PubMed

Skulan, J; DePaolo, D J

1999-11-23

Calcium from bone and shell is isotopically lighter than calcium of soft tissue from the same organism and isotopically lighter than source (dietary) calcium. When measured as the (44)Ca/(40)Ca isotopic ratio, the total range of variation observed is 5.5 per thousand, and as much as 4 per thousand variation is found in a single organism. The observed intraorganismal calcium isotopic variations and the isotopic differences between tissues and diet indicate that isotopic fractionation occurs mainly as a result of mineralization. Soft tissue calcium becomes heavier or lighter than source calcium during periods when there is net gain or loss of mineral mass, respectively. These results suggest that variations of natural calcium isotope ratios in tissues may be useful for assessing the calcium and mineral balance of organisms without introducing isotopic tracers.

Calcium isotope fractionation between soft and mineralized tissues as a monitor of calcium use in vertebrates

PubMed Central

Skulan, Joseph; DePaolo, Donald J.

1999-01-01

Calcium from bone and shell is isotopically lighter than calcium of soft tissue from the same organism and isotopically lighter than source (dietary) calcium. When measured as the 44Ca/40Ca isotopic ratio, the total range of variation observed is 5.5‰, and as much as 4‰ variation is found in a single organism. The observed intraorganismal calcium isotopic variations and the isotopic differences between tissues and diet indicate that isotopic fractionation occurs mainly as a result of mineralization. Soft tissue calcium becomes heavier or lighter than source calcium during periods when there is net gain or loss of mineral mass, respectively. These results suggest that variations of natural calcium isotope ratios in tissues may be useful for assessing the calcium and mineral balance of organisms without introducing isotopic tracers. PMID:10570137

The ERM protein Moesin is essential for neuronal morphogenesis and long-term memory in Drosophila.

PubMed

Freymuth, Patrick S; Fitzsimons, Helen L

2017-08-29

Moesin is a cytoskeletal adaptor protein that plays an important role in modification of the actin cytoskeleton. Rearrangement of the actin cytoskeleton drives both neuronal morphogenesis and the structural changes in neurons that are required for long-term memory formation. Moesin has been identified as a candidate memory gene in Drosophila, however, whether it is required for memory formation has not been evaluated. Here, we investigate the role of Moesin in neuronal morphogenesis and in short- and long-term memory formation in the courtship suppression assay, a model of associative memory. We found that both knockdown and overexpression of Moesin led to defects in axon growth and guidance as well as dendritic arborization. Moreover, reduction of Moesin expression or expression of a constitutively active phosphomimetic in the adult Drosophila brain had no effect on short term memory, but prevented long-term memory formation, an effect that was independent of its role in development. These results indicate a critical role for Moesin in both neuronal morphogenesis and long-term memory formation.

Plant Growth and Morphogenesis under Different Gravity Conditions: Relevance to Plant Life in Space.

PubMed

Hoson, Takayuki

2014-05-16

The growth and morphogenesis of plants are entirely dependent on the gravitational acceleration of earth. Under microgravity conditions in space, these processes are greatly modified. Recent space experiments, in combination with ground-based studies, have shown that elongation growth is stimulated and lateral expansion suppressed in various shoot organs and roots under microgravity conditions. Plant organs also show automorphogenesis in space, which consists of altered growth direction and spontaneous curvature in the dorsiventral (back and front) directions. Changes in cell wall properties are responsible for these modifications of growth and morphogenesis under microgravity conditions. Plants live in space with interesting new sizes and forms.

Prevalence of vertebral fracture and densitometric osteoporosis in Spanish adult men: The Camargo Cohort Study.

PubMed

Olmos, José M; Hernández, José L; Martínez, Josefina; Pariente, Emilio; Castillo, Jesús; Prieto-Alhambra, Daniel; González-Macías, Jesús

2018-01-01

The aim of this study was to assess the prevalence of densitometric osteoporosis and vertebral fractures in Spanish men aged ≥50 years, and to study how the relationship between them may change depending on how osteoporosis is diagnosed. A community-based population of 1003 men aged ≥50 years was studied. Bone mineral density (BMD) was measured by DXA at the lumbar spine, femoral neck and total hip. Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs. The prevalence of osteoporosis was estimated with both the World Health Organization (WHO) (T-score of <-2.5 at the femoral neck, calculated using the young white female normal reference database) and the National Osteoporosis Foundation (NOF) criteria (T-score of <-2.5 at the femoral neck, total hip or lumbar spine, calculated using the young white male normal reference database). The prevalence of osteoporosis using the WHO criterion was 1.1% and using the NOF criterion was 13%, while that of vertebral fractures was 21.3%. The area under the curve (AUC) for the relationship between BMD and vertebral fracture prevalence was 0.64. The odds ratio for osteoporosis using the WHO definition was 2.57 (p = 0.13), and 1.78 (p = 0.007) using the NOF definition. Vertebral fracture prevalence rose with age. The prevalence of osteoporosis increased only moderately in men aged >70 years with the WHO criterion, and showed no change using the NOF definition. The prevalence of osteoporosis in Spanish men using the WHO definition is too small to have any meaningful clinical use. Although the figure is higher using the NOF definition, it would seem that population-based studies of BMD in men are of questionable value.

Gastrulation and pre-gastrulation morphogenesis, inductions, and gene expression: similarities and dissimilarities between urodelean and anuran embryos.

PubMed

Kaneda, Teruo; Motoki, Jun-ya Doi

2012-09-01

Studies of meso-endoderm and neural induction and subsequent body plan formation have been analyzed using mainly amphibians as the experimental model. Xenopus is currently the predominant model, because it best enables molecular analysis of these induction processes. However, much of the embryological information on these inductions (e.g., those of the Spemann-Mangold organizer), and on the morphogenetic movements of inductively interacting tissues, derives from research on non-model amphibians, especially urodeles. Although the final body pattern is strongly conserved in vertebrates, and although many of the same developmental genes are expressed, it has become evident that there are individually diverse modes of morphogenesis and timing of developmental events. Whether or not this diversity represents essential differences in the early induction processes remains unclear. The aim of this review is to compare the gastrulation process, induction processes, and gene expressions between a urodele, mainly Cynops pyrrhogaster, and an anura, Xenopus laevis, thereby to clarify conserved and diversified aspects. Cynops gastrulation differs significantly from that of Xenopus in that specification of the regions of the Xenopus dorsal marginal zone (DMZ) are specified before the onset of gastrulation, as marked by blastopore formation, whereas the equivalent state of specification does not occur in Cynops until the middle of gastrulation. Detailed comparison of the germ layer structure and morphogenetic movements during the pre-gastrula and gastrula stages shows that the entire gastrulation process should be divided into two phases of notochord induction and neural induction. Cynops undergoes these processes sequentially after the onset of gastrulation, whereas Xenopus undergoes notochord induction during a series of pre-gastrulation movements, and its traditionally defined period of gastrulation only includes the neural induction phase. Comparing the structure, fate

The posterior skeletal thorax: rib-vertebral angle and axial vertebral rotation asymmetries in adolescent idiopathic scoliosis.

PubMed

Burwell, R G; Aujla, R K; Freeman, B J C; Dangerfield, P H; Cole, A A; Kirby, A S; Polak, F J; Pratt, R K; Moulton, A

2008-01-01

The deformity of the ribcage in thoracic adolescent idiopathic scoliosis (AIS) is viewed by most as being secondary to the spinal deformity, though a few consider it primary or involved in curve aggravation. Those who consider it primary ascribe pathogenetic significance to rib-vertebra angle asymmetry. In thoracic AIS, supra-apical rib-vertebra angle differences (RVADs) are reported to be associated with the severity of the Cobb angle. In this paper we attempt to evaluate rib and spinal pathomechanisms in thoracic and thnoracolumbar AIS using spinal radiographs and real-time ultrasound. On the radiographs by costo-vertebral angle asymmetries (rib-vertebral angle differences RVADs, and rib-spinal angle differences RSADs), apical vertebral rotation (AV) and apical vertebral translation (AVT) were measured; and by ultrasound, spine-rib rotation differences (SRRDs) were estimated. RVADs are largest at two and three vertebral levels above the apex where they correlate significantly and positively with Cobb angle and AVT but not AVR. In right thoracic AIS, the cause(s) of the RVA asymmetries is unknown: it may result from trunk muscle imbalance, or from ribs adjusting passively within the constraint of the fourth column of the spine to increasing spinal curvature from whatever cause. Several possible mechanisms may drive axial vertebral rotation including, biplanar spinal asymmetry, relative anterior spinal overgrowth, dorsal shear forces in the presence of normal vertebral axial rotation, asymmetry of rib linear growth, trunk muscle imbalance causing rib-vertebra angle asymmetry weakening the spinal rotation-defending system of bipedal gait, and CNS mechanisms.

Importance of MAP Kinases during Protoperithecial Morphogenesis in Neurospora crassa

PubMed Central

Jeffree, Chris E.; Oborny, Radek; Boonyarungsrit, Patid; Read, Nick D.

2012-01-01

In order to produce multicellular structures filamentous fungi combine various morphogenetic programs that are fundamentally different from those used by plants and animals. The perithecium, the female sexual fruitbody of Neurospora crassa, differentiates from the vegetative mycelium in distinct morphological stages, and represents one of the more complex multicellular structures produced by fungi. In this study we defined the stages of protoperithecial morphogenesis in the N. crassa wild type in greater detail than has previously been described; compared protoperithecial morphogenesis in gene-deletion mutants of all nine mitogen-activated protein (MAP) kinases conserved in N. crassa; confirmed that all three MAP kinase cascades are required for sexual development; and showed that the three different cascades each have distinctly different functions during this process. However, only MAP kinases equivalent to the budding yeast pheromone response and cell wall integrity pathways, but not the osmoregulatory pathway, were essential for vegetative cell fusion. Evidence was obtained for MAP kinase signaling cascades performing roles in extracellular matrix deposition, hyphal adhesion, and envelopment during the construction of fertilizable protoperithecia. PMID:22900028

CIRSE Guidelines on Percutaneous Vertebral Augmentation

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

Tsoumakidou, Georgia, E-mail: gtsoumakidou@yahoo.com; Too, Chow Wei, E-mail: spyder55@gmail.com; Koch, Guillaume, E-mail: guillaume.koch@gmail.com

Vertebral compression fracture (VCF) is an important cause of severe debilitating back pain, adversely affecting quality of life, physical function, psychosocial performance, mental health and survival. Different vertebral augmentation procedures (VAPs) are used in order to consolidate the VCFs, relief pain,and whenever posible achieve vertebral body height restoration. In the present review we give the indications, contraindications, safety profile and outcomes of the existing percutaneous VAPs.

Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

PubMed

Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

2017-12-29

Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure.

Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns Tell Us?

PubMed Central

Schweickert, Axel; Ott, Tim; Kurz, Sabrina; Tingler, Melanie; Maerker, Markus; Fuhl, Franziska; Blum, Martin

2017-01-01

Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure. PMID:29367579

Light adaptation and the evolution of vertebrate photoreceptors.

PubMed

Morshedian, Ala; Fain, Gordon L

2017-07-15

Lamprey are cyclostomes, a group of vertebrates that diverged from lines leading to jawed vertebrates (including mammals) in the late Cambrian, 500 million years ago. It may therefore be possible to infer properties of photoreceptors in early vertebrate progenitors by comparing lamprey to other vertebrates. We show that lamprey rods and cones respond to light much like rods and cones in amphibians and mammals. They operate over a similar range of light intensities and adapt to backgrounds and bleaches nearly identically. These correspondences are pervasive and detailed; they argue for the presence of rods and cones very early in the evolution of vertebrates with properties much like those of rods and cones in existing vertebrate species. The earliest vertebrates were agnathans - fish-like organisms without jaws, which first appeared near the end of the Cambrian radiation. One group of agnathans became cyclostomes, which include lamprey and hagfish. Other agnathans gave rise to jawed vertebrates or gnathostomes, the group including all other existing vertebrate species. Because cyclostomes diverged from other vertebrates 500 million years ago, it may be possible to infer some of the properties of the retina of early vertebrate progenitors by comparing lamprey to other vertebrates. We have previously shown that rods and cones in lamprey respond to light much like photoreceptors in other vertebrates and have a similar sensitivity. We now show that these affinities are even closer. Both rods and cones adapt to background light and to bleaches in a manner almost identical to other vertebrate photoreceptors. The operating range in darkness is nearly the same in lamprey and in amphibian or mammalian rods and cones; moreover background light shifts response-intensity curves downward and to the right over a similar range of ambient intensities. Rods show increment saturation at about the same intensity as mammalian rods, and cones never saturate. Bleaches decrease

Pregnancy-associated osteoporosis presenting severe vertebral fractures.

PubMed

Ozturk, Cihat; Atamaz, Funda Calis; Akkurt, Halil; Akkoc, Yesim

2014-01-01

The syndrome of pregnancy-associated osteoporosis (PAO) is a rare disorder which occurs either in late pregnancy or early post-partum period leading to fragility fracture(s), most commonly in the vertebral bodies. We presented two cases with PAO who had compression fractures at multiple levels involving five vertebrae in one case and 10 vertebrae in the other. Their spinal bone mineral density values were below -2.5 standard deviations. Anti-osteoporotic treatments with nasal calcitonin 400 IU/day, vitamin D 300.000 IU single dose, calcium 1000 mg/day, vitamin D 880 IU/day were initiated. In one case, kyphoplasty was performed by a spinal surgeon. In addition to a thoracolumbosacral orthosis, a rehabilitation program including muscle strengthening, range of motion, relaxation and weight-bearing exercises was started for both cases. These cases emphasize that all pregnant women with complaints of back/lumbar pain should be carefully evaluated. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Embryonic origin of the gnathostome vertebral skeleton

PubMed Central

Gillis, J. Andrew

2017-01-01

The vertebral column is a key component of the jawed vertebrate (gnathostome) body plan, but the primitive embryonic origin of this skeleton remains unclear. In tetrapods, all vertebral components (neural arches, haemal arches and centra) derive from paraxial mesoderm (somites). However, in teleost fishes, vertebrae have a dual embryonic origin, with arches derived from somites, but centra formed, in part, by secretion of bone matrix from the notochord. Here, we test the embryonic origin of the vertebral skeleton in a cartilaginous fish (the skate, Leucoraja erinacea) which serves as an outgroup to tetrapods and teleosts. We demonstrate, by cell lineage tracing, that both arches and centra are somite-derived. We find no evidence of cellular or matrix contribution from the notochord to the skate vertebral skeleton. These findings indicate that the earliest gnathostome vertebral skeleton was exclusively of somitic origin, with a notochord contribution arising secondarily in teleosts. PMID:29167367

The evolution of vertebral formulae in Hominoidea.

PubMed

Thompson, Nathan E; Almécija, Sergio

2017-09-01

Primate vertebral formulae have long been investigated because of their link to locomotor behavior and overall body plan. Knowledge of the ancestral vertebral formulae in the hominoid tree of life is necessary to interpret the pattern of evolution among apes, and to critically evaluate the morphological adaptations involved in the transition to hominin bipedalism. Though many evolutionary hypotheses have been proposed based on living and fossil species, the application of quantitative phylogenetic methods for thoroughly reconstructing ancestral vertebral formulae and formally testing patterns of vertebral evolution is lacking. To estimate the most probable scenarios of hominoid vertebral evolution, we utilized an iterative ancestral state reconstruction approach to determine likely ancestral vertebral counts in apes, humans, and other anthropoid out-groups. All available ape and hominin fossil taxa with an inferred regional vertebral count were included in the analysis. Sensitivity iterations were performed both by changing the phylogenetic position of fossil taxa with a contentious placement, and by changing the inferred number of vertebrae in taxa with uncertain morphology. Our ancestral state reconstruction results generally support a short-backed hypothesis of human evolution, with a Pan-Homo last common ancestor possessing a vertebral formulae of 7:13:4:6 (cervical:thoracic:lumbar:sacral). Our results indicate that an initial reduction in lumbar vertebral count and increase in sacral count is a synapomorphy of crown hominoids (supporting an intermediate-backed hypothesis for the origins of the great ape-human clade). Further reduction in lumbar count occurs independently in orangutans and African apes. Our results highlight the complexity and homoplastic nature of vertebral count evolution, and give little support to the long-backed hypothesis of human evolution. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bacterial Community Morphogenesis Is Intimately Linked to the Intracellular Redox State

PubMed Central

Okegbe, Chinweike; Price-Whelan, Alexa; Sakhtah, Hassan; Hunter, Ryan C.; Newman, Dianne K.

2013-01-01

Many microbial species form multicellular structures comprising elaborate wrinkles and concentric rings, yet the rules governing their architecture are poorly understood. The opportunistic pathogen Pseudomonas aeruginosa produces phenazines, small molecules that act as alternate electron acceptors to oxygen and nitrate to oxidize the intracellular redox state and that influence biofilm morphogenesis. Here, we show that the depth occupied by cells within colony biofilms correlates well with electron acceptor availability. Perturbations in the environmental provision, endogenous production, and utilization of electron acceptors affect colony development in a manner consistent with redox control. Intracellular NADH levels peak before the induction of colony wrinkling. These results suggest that redox imbalance is a major factor driving the morphogenesis of P. aeruginosa biofilms and that wrinkling itself is an adaptation that maximizes oxygen accessibility and thereby supports metabolic homeostasis. This type of redox-driven morphological change is reminiscent of developmental processes that occur in metazoans. PMID:23292774

The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza1

PubMed Central

Rich, Mélanie K.

2015-01-01

Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex symbiotic interface over which nutrients are exchanged between the plant host and the AM fungus. Dozens of genes in the host are required for the establishment and functioning of the interaction, among them nutrient transporters that mediate the uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated in a genetic mutant screen a petunia (Petunia hybrida) GIBBERELLIC ACID INSENSITIVE, REPRESSOR of GIBBERELLIC ACID INSENSITIVE, and SCARECROW (GRAS)-type transcription factor, ATYPICAL ARBUSCULE (ATA), that acts as the central regulator of AM-related genes and is required for the morphogenesis of arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants revealed an additional role of ATA in restricting mycorrhizal colonization of the root meristem. The lack of ATA, which represents the ortholog of REQUIRED FOR ARBUSCULAR MYCORRHIZA1 in Medicago truncatula, renders the interaction completely ineffective, hence demonstrating the central role of AM-related genes for arbuscule development and function. PMID:25971550

Notochord morphogenesis in mice: Current understanding & open questions.

PubMed

Balmer, Sophie; Nowotschin, Sonja; Hadjantonakis, Anna-Katerina

2016-05-01

The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Chondroitin 6-O-sulfotransferases are required for morphogenesis of the notochord in the ascidian embryo.

PubMed

Nakamura, Jun; Yoshida, Keita; Sasakura, Yasunori; Fujiwara, Shigeki

2014-12-01

Chondroitin sulfate (CS) is a sulfated polysaccharide chain that binds to various core proteins to form proteoglycans. The amount and position of sulfate groups in CS are variable among different tissues, and are determined by specific sulfotransferases. Although the ascidians are the closest relatives of vertebrates, the functions of their sulfotransferases have not been studied. The genome of the ascidian Ciona intestinalis contains eight genes encoding proteins similar to chondroitin 6-O-sulfotransferases (C6STs), which appear to have independently diverged in the ascidian lineage during evolution. Among them, Ci-C6ST-like1 and Ci-C6ST-like7 were predominantly expressed in the developing notochord. In addition, they were weakly expressed in the neural tube. The disruption of either one of them affected the convergent extension movement of notochordal cells. Presumptive notochord cells coming from both sides of the embryo did not intercalate. The results suggest that both of them are necessary. In some cases, the anterior neural tube failed to close. Forced expression of Ci-C6ST-like1 or Ci-C6ST-like7 in the notochord restored the normal intercalation of notochordal cells, indicating that the effects of morpholino oligos are specific. Ci-C6ST-like1 and Ci-C6ST-like7 are required for the morphogenesis of the notochord in the ascidian embryo. © 2014 Wiley Periodicals, Inc.

Lymphatic regulation in nonmammalian vertebrates.

PubMed

Hedrick, Michael S; Hillman, Stanley S; Drewes, Robert C; Withers, Philip C

2013-08-01

All vertebrate animals share in common the production of lymph through net capillary filtration from their closed circulatory system into their tissues. The balance of forces responsible for net capillary filtration and lymph formation is described by the Starling equation, but additional factors such as vascular and interstitial compliance, which vary markedly among vertebrates, also have a significant impact on rates of lymph formation. Why vertebrates show extreme variability in rates of lymph formation and how nonmammalian vertebrates maintain plasma volume homeostasis is unclear. This gap hampers our understanding of the evolution of the lymphatic system and its interaction with the cardiovascular system. The evolutionary origin of the vertebrate lymphatic system is not clear, but recent advances suggest common developmental factors for lymphangiogenesis in teleost fishes, amphibians, and mammals with some significant changes in the water-land transition. The lymphatic system of anuran amphibians is characterized by large lymphatic sacs and two pairs of lymph hearts that return lymph into the venous circulation but no lymph vessels per se. The lymphatic systems of reptiles and some birds have lymph hearts, and both groups have extensive lymph vessels, but their functional role in both lymph movement and plasma volume homeostasis is almost completely unknown. The purpose of this review is to present an evolutionary perspective in how different vertebrates have solved the common problem of the inevitable formation of lymph from their closed circulatory systems and to point out the many gaps in our knowledge of this evolutionary progression.

Nanotechnology for treating osteoporotic vertebral fractures

PubMed Central

Gao, Chunxia; Wei, Donglei; Yang, Huilin; Chen, Tao; Yang, Lei

2015-01-01

Osteoporosis is a serious public health problem affecting hundreds of millions of aged people worldwide, with severe consequences including vertebral fractures that are associated with significant morbidity and mortality. To augment or treat osteoporotic vertebral fractures, a number of surgical approaches including minimally invasive vertebroplasty and kyphoplasty have been developed. However, these approaches face problems and difficulties with efficacy and long-term stability. Recent advances and progress in nanotechnology are opening up new opportunities to improve the surgical procedures for treating osteoporotic vertebral fractures. This article reviews the improvements enabled by new nanomaterials and focuses on new injectable biomaterials like bone cements and surgical instruments for treating vertebral fractures. This article also provides an introduction to osteoporotic vertebral fractures and current clinical treatments, along with the rationale and efficacy of utilizing nanomaterials to modify and improve biomaterials or instruments. In addition, perspectives on future trends with injectable bone cements and surgical instruments enhanced by nanotechnology are provided. PMID:26316746

Vertebral architecture in the earliest stem tetrapods.

PubMed

Pierce, Stephanie E; Ahlberg, Per E; Hutchinson, John R; Molnar, Julia L; Sanchez, Sophie; Tafforeau, Paul; Clack, Jennifer A

2013-02-14

The construction of the vertebral column has been used as a key anatomical character in defining and diagnosing early tetrapod groups. Rhachitomous vertebrae--in which there is a dorsally placed neural arch and spine, an anteroventrally placed intercentrum and paired, posterodorsally placed pleurocentra--have long been considered the ancestral morphology for tetrapods. Nonetheless, very little is known about vertebral anatomy in the earliest stem tetrapods, because most specimens remain trapped in surrounding matrix, obscuring important anatomical features. Here we describe the three-dimensional vertebral architecture of the Late Devonian stem tetrapod Ichthyostega using propagation phase-contrast X-ray synchrotron microtomography. Our scans reveal a diverse array of new morphological, and associated developmental and functional, characteristics, including a possible posterior-to-anterior vertebral ossification sequence and the first evolutionary appearance of ossified sternal elements. One of the most intriguing features relates to the positional relationships between the vertebral elements, with the pleurocentra being unexpectedly sutured or fused to the intercentra that directly succeed them, indicating a 'reverse' rhachitomous design. Comparison of Ichthyostega with two other stem tetrapods, Acanthostega and Pederpes, shows that reverse rhachitomous vertebrae may be the ancestral condition for limbed vertebrates. This study fundamentally revises our current understanding of vertebral column evolution in the earliest tetrapods and raises questions about the presumed vertebral architecture of tetrapodomorph fish and later, more crownward, tetrapods.

Alternative approaches for vertebrate ecotoxicity tests in the ...

EPA Pesticide Factsheets

The need for alternative approaches to the use of vertebrate animals for hazard assessing chemicals and pollutants has become of increasing importance. It is now the first consideration when initiating a vertebrate ecotoxicity test, to ensure that unnecessary use of vertebrate organisms is minimised wherever possible. For some regulatory purposes, the use of vertebrate organisms for environmental risk assessments (ERA) has even been banned, and in other situations the numbers of organisms tested has been dramatically reduced, or the severity of the procedure refined. However, there is still a long way to go to achieve replacement of vertebrate organisms to generate environmental hazard data. The development of animal alternatives is not just based on ethical considerations but also to reduce the cost of performing vertebrate ecotoxicity tests and in some cases to provide better information aimed at improving ERAs. The present focus paper provides an overview of the considerable advances that have been made towards alternative approaches for ecotoxicity assessments over the last few decades. The need for alternative approaches to the use of vertebrate animals for hazard assessing chemicals and pollutants has become of increasing importance. It is now the first consideration when initiating a vertebrate ecotoxicity test, to ensure that unnecessary use of vertebrate organisms is minimised wherever possible. For some regulatory purposes, the use of vertebrate organi

Reconstruction of the vertebrate ancestral genome reveals dynamic genome reorganization in early vertebrates.

PubMed

Nakatani, Yoichiro; Takeda, Hiroyuki; Kohara, Yuji; Morishita, Shinichi

2007-09-01

Although several vertebrate genomes have been sequenced, little is known about the genome evolution of early vertebrates and how large-scale genomic changes such as the two rounds of whole-genome duplications (2R WGD) affected evolutionary complexity and novelty in vertebrates. Reconstructing the ancestral vertebrate genome is highly nontrivial because of the difficulty in identifying traces originating from the 2R WGD. To resolve this problem, we developed a novel method capable of pinning down remains of the 2R WGD in the human and medaka fish genomes using invertebrate tunicate and sea urchin genes to define ohnologs, i.e., paralogs produced by the 2R WGD. We validated the reconstruction using the chicken genome, which was not considered in the reconstruction step, and observed that many ancestral proto-chromosomes were retained in the chicken genome and had one-to-one correspondence to chicken microchromosomes, thereby confirming the reconstructed ancestral genomes. Our reconstruction revealed a contrast between the slow karyotype evolution after the second WGD and the rapid, lineage-specific genome reorganizations that occurred in the ancestral lineages of major taxonomic groups such as teleost fishes, amphibians, reptiles, and marsupials.

Vertebral sclerosis in adults.

PubMed Central

Russell, A S; Percy, J S; Lentle, B C

1979-01-01

Narrowing of the intervertebral disc space with sclerosis of the adjacent vertebral bodies may occur as a consequence of infection, neoplasia, trauma, or rheumatic disease. Some patients have been described with backache and these radiological appearances without any primary cause being apparent. The lesions were almost always of 1 or, at most, 2 vertebrae and most frequently involved the inferior margin of L4. We describe 3 patients with far more extensive vertebral involvement and present the clinical, radiological, scintiscan, and histological findings. The only patient we have seen with the better known, isolated L4/5 lesion was shown on biopsy to have staphylococcal osteomyelitis. For this reason we would still recommend a biopsy of all such sclerotic vertebral lesions if they occur in the absence of other rheumatic disease. Images PMID:434941

Behavioral fever in ectothermic vertebrates.

PubMed

Rakus, Krzysztof; Ronsmans, Maygane; Vanderplasschen, Alain

2017-01-01

Fever is an evolutionary conserved defense mechanism which is present in both endothermic and ectothermic vertebrates. Ectotherms in response to infection can increase their body temperature by moving to warmer places. This process is known as behavioral fever. In this review, we summarize the current knowledge on the mechanisms of induction of fever in mammals. We further discuss the evolutionary conserved mechanisms existing between fever of mammals and behavioral fever of ectothermic vertebrates. Finally, the experimental evidences supporting an adaptive value of behavioral fever expressed by ectothermic vertebrates are summarized. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Morphogenesis in formative process in vitro from Rehmannia glutinosa].

PubMed

Xue, Jian-ping; Zhang, Ai-min; Liu, Jun; Xu, Xue-feng

2004-01-01

To study the morphogenesis in formative process of tuberous root in vitro from Rehmannia glutinosa and compare the anatomical shape of tuberous root with nature term R. glutinosa. Tuberous roots of different vegetal phase were cut and dyed, then made into paraffin cuts and observed microscope. In anatomical shape, nature R. glutinosa and tuberous root were the same, which showed that no structural variation occurred in tuberous root induced process.

Interference by 2,3,7,8-tetrachlorodibenzo-p-dioxin with cultured mouse submandibular gland branching morphogenesis involves reduced epidermal growth factor receptor signaling

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

Kiukkonen, Anu; Sahlberg, Carin; Partanen, Anna-Maija

2006-05-01

Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to mouse embryonic teeth, sharing features of early development with salivary glands in common, involves enhanced apoptosis and depends on the expression of epidermal growth factor (EGF) receptor. EGF receptor signaling, on the other hand, is essential for salivary gland branching morphogenesis. To see if TCDD impairs salivary gland morphogenesis and if the impairment is associated with EGF receptor signaling, we cultured mouse (NMRI) E13 submandibular glands with TCDD or TCDD in combination with EGF or fibronectin (FN), both previously found to enhance branching morphogenesis. Explants were examined stereomicroscopically and processed to paraffin sections. TCDD exposuremore » impaired epithelial branching and cleft formation, resulting in enlarged buds. The glands were smaller than normal. EGF and FN alone concentration-dependently stimulated or inhibited branching morphogenesis but when co-administered with TCDD, failed to compensate for its effect. TCDD induced cytochrome P4501A1 expression in the glandular epithelium, indicating activation of the aryl hydrocarbon receptor. TCDD somewhat increased epithelial apoptosis as observed by terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling method but the increase could not be correlated with morphological changes. The frequency of proliferating cells was not altered. Corresponding to the reduced cleft sites in TCDD-exposed explants, FN immunoreactivity in the epithelium was reduced. The results show that TCDD, comparably with EGF and FN at morphogenesis-inhibiting concentrations, impaired salivary gland branching morphogenesis in vitro. Together with the failure of EGF and FN at morphogenesis-stimulating concentrations to compensate for the effect of TCDD this implies that TCDD toxicity to developing salivary gland involves reduced EGF receptor signaling.« less

Functional Role of the microRNA-200 Family in Breast Morphogenesis and Neoplasia

PubMed Central

Hilmarsdottir, Bylgja; Briem, Eirikur; Bergthorsson, Jon Thor; Magnusson, Magnus Karl; Gudjonsson, Thorarinn

2014-01-01

Branching epithelial morphogenesis is closely linked to epithelial-to-mesenchymal transition (EMT), a process important in normal development and cancer progression. The miR-200 family regulates epithelial morphogenesis and EMT through a negative feedback loop with the ZEB1 and ZEB2 transcription factors. miR-200 inhibits expression of ZEB1/2 mRNA, which in turn can down-regulate the miR-200 family that further results in down-regulation of E-cadherin and induction of a mesenchymal phenotype. Recent studies show that the expression of miR-200 genes is high during late pregnancy and lactation, thereby indicating that these miRs are important for breast epithelial morphogenesis and differentiation. miR-200 genes have been studied intensively in relation to breast cancer progression and metastasis, where it has been shown that miR-200 members are down-regulated in basal-like breast cancer where the EMT phenotype is prominent. There is growing evidence that the miR-200 family is up-regulated in distal breast metastasis indicating that these miRs are important for colonization of metastatic breast cancer cells through induction of mesenchymal to epithelial transition. The dual role of miR-200 in primary and metastatic breast cancer is of interest for future therapeutic interventions, making it important to understand its role and interacting partners in more detail. PMID:25216122

A contribution with review to the description of mineralization of bone and other calcified tissues in vivo

NASA Technical Reports Server (NTRS)

Christoffersen, J.; Landis, W. J.

1991-01-01

This manuscript considers certain aspects of mineral deposition in bone and other vertebrate calcifying tissues in order to examine physical, chemical, and biological factors important in the mineralization process. The paper in a discussion format principally presents a new data and the formulation of concepts based on such data as well as a summary of background material as necessary review. Mineralization is found to occur at spatially independent sites throughout the organic extracellular tissue matrices. Matrix vesicles and collagen fibrils each may serve as independent nucleation centers for mineral with vesicle mineralization being local and collagen mineralization dominating the tissues as a whole. Collagen fibril organization is suggested to be such that hole zones are aligned in three dimensions, creating extensive channels for mineral accommodation. Nucleation occurs initially in hole zones and crystal growth leads to the development of plate-like mineral particles whose orientation, disposition, and sizes within fibrils are detailed. Effects of diffusion, crystallinity, and critical nucleation and growth events are described with respect to their influence on mineral deposition in bulk and local regions of tissue matrices.

Regulation of cellulase expression, sporulation, and morphogenesis by velvet family proteins in Trichoderma reesei.

PubMed

Liu, Kuimei; Dong, Yanmei; Wang, Fangzhong; Jiang, Baojie; Wang, Mingyu; Fang, Xu

2016-01-01

Homologs of the velvet protein family are encoded by the ve1, vel2, and vel3 genes in Trichoderma reesei. To test their regulatory functions, the velvet protein-coding genes were disrupted, generating Δve1, Δvel2, and Δvel3 strains. The phenotypic features of these strains were examined to identify their functions in morphogenesis, sporulation, and cellulase expression. The three velvet-deficient strains produced more hyphal branches, indicating that velvet family proteins participate in the morphogenesis in T. reesei. Deletion of ve1 and vel3 did not affect biomass accumulation, while deletion of vel2 led to a significantly hampered growth when cellulose was used as the sole carbon source in the medium. The deletion of either ve1 or vel2 led to the sharp decrease of sporulation as well as a global downregulation of cellulase-coding genes. In contrast, although the expression of cellulase-coding genes of the ∆vel3 strain was downregulated in the dark, their expression in light condition was unaffected. Sporulation was hampered in the ∆vel3 strain. These results suggest that Ve1 and Vel2 play major roles, whereas Vel3 plays a minor role in sporulation, morphogenesis, and cellulase expression.

Differentiated roles for MreB-actin isologues and autolytic enzymes in Bacillus subtilis morphogenesis.

PubMed

Domínguez-Cuevas, Patricia; Porcelli, Ida; Daniel, Richard A; Errington, Jeff

2013-09-01

Cell morphogenesis in most bacteria is governed by spatiotemporal growth regulation of the peptidoglycan cell wall layer. Much is known about peptidoglycan synthesis but regulation of its turnover by hydrolytic enzymes is much less well understood. Bacillus subtilis has a multitude of such enzymes. Two of the best characterized are CwlO and LytE: cells lacking both enzymes have a lethal block in cell elongation. Here we show that activity of CwlO is regulated by an ABC transporter, FtsEX, which is required for cell elongation, unlike cell division as in Escherichia coli. Actin-like MreB proteins are thought to play a key role in orchestrating cell wall morphogenesis. B. subtilis has three MreB isologues with partially differentiated functions. We now show that the three MreB isologues have differential roles in regulation of the CwlO and LytE systems and that autolysins control different aspects of cell morphogenesis. The results add major autolytic activities to the growing list of functions controlled by MreB isologues in bacteria and provide new insights into the different specialized functions of essential cell wall autolysins. © 2013 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.

The association between genetic variants of RUNX2, ADIPOQ and vertebral fracture in Korean postmenopausal women.

PubMed

Kim, Kyong-Chol; Chun, Hyejin; Lai, ChaoQiang; Parnell, Laurence D; Jang, Yangsoo; Lee, Jongho; Ordovas, Jose M

2015-03-01

Contrary to the traditional belief that obesity acts as a protective factor for bone, recent epidemiologic studies have shown that body fat might be a risk factor for osteoporosis and bone fracture. Accordingly, we evaluated the association between the phenotypes of osteoporosis or vertebral fracture and variants of obesity-related genes, peroxisome proliferator-activated receptor-gamma (PPARG), runt-related transcription factor 2 (RUNX2), leptin receptor (LEPR), and adiponectin (ADIPOQ). In total, 907 postmenopausal healthy women, aged 60-79 years, were included in this study. BMD and biomarkers of bone health and adiposity were measured. We genotyped for four single nucleotide polymorphisms (SNPs) from four genes (PPARG, RUNX2, LEPR, ADIPOQ). A general linear model for continuous dependent variables and a logistic regression model for categorical dependent variables were used to analyze the statistical differences among genotype groups. Compared with the TT subjects at rs7771980 in RUNX2, C-carrier (TC + CC) subjects had a lower vertebral fracture risk after adjusting for age, smoking, alcohol, total calorie intake, total energy expenditure, total calcium intake, total fat intake, weight, body fat. Odds ratio (OR) and 95% interval (CI) for the vertebral fracture risk was 0.55 (95% CI 0.32-0.94). After adjusting for multiple variables, the prevalence of vertebral fracture was highest in GG subjects at rs1501299 in ADIPOQ (p = 0.0473). A high calcium intake (>1000 mg/day) contributed to a high bone mineral density (BMD) in GT + TT subjects at rs1501299 in ADIPOQ (p for interaction = 0.0295). Even if the mechanisms between obesity-related genes and bone health are not fully established, the results of our study revealed the association of certain SNPs from obesity-related genes with BMD or vertebral fracture risk in postmenopausal Korean women.

Department of Vertebrate Zoology, NMNH

Science.gov Websites

Research & Collections About Us Get Involved Calendar Department ofVertebrate Zoology Red-eyed Libraries Staff Contact Us NMNH Home › Research & Collections › Department of Vertebrate Zoology the study of animals with backbones. Research in the department covers fishes, amphibians, reptiles

Growth and morphogenesis of embryonic mouse organs on non-coated and extracellular matrix-coated Biopore membrane

NASA Technical Reports Server (NTRS)

Hardman, P.; Klement, B. J.; Spooner, B. S.

1993-01-01

Embryonic mouse salivary glands, pancreata, and kidneys were isolated from embryos of appropriate gestational age by microdissection, and were cultured on Biopore membrane either non-coated or coated with type I collagen or Matrigel. As expected, use of Biopore membrane allowed high quality photomicroscopy of the living organs. In all organs extensive mesenchymal spreading was observed in the presence of type I collagen or Matrigel. However, differences were noted in the effects of extracellular matrix (ECM) coatings on epithelial growth and morphogenesis: salivary glands were minimally affected, pancreas morphogenesis was adversely affected, and kidney growth and branching apparently was enhanced. It is suggested that these differences in behaviour reflect differences in the strength of interactions between the mesenchymal cells and their surrounding endogenous matrix, compared to the exogenous ECM macromolecules. This method will be useful for culture of these and other embryonic organs. In particular, culture of kidney rudiments on ECM-coated Biopore offers a great improvement over previously used methods which do not allow morphogenesis to be followed in vitro.

Quantum morphogenesis: A variation on Thom's catastrophe theory

NASA Astrophysics Data System (ADS)

Aerts, Dirk; Czachor, Marek; Gabora, Liane; Kuna, Maciej; Posiewnik, Andrzej; Pykacz, Jarosław; Syty, Monika

2003-05-01

Noncommutative propositions are characteristic of both quantum and nonquantum (sociological, biological, and psychological) situations. In a Hilbert space model, states, understood as correlations between all the possible propositions, are represented by density matrices. If systems in question interact via feedback with environment, their dynamics is nonlinear. Nonlinear evolutions of density matrices lead to the phenomenon of morphogenesis that may occur in noncommutative systems. Several explicit exactly solvable models are presented, including “birth and death of an organism” and “development of complementary properties.”

Variation of canine vertebral bone architecture in computed tomography

PubMed Central

Cheon, Byunggyu; Park, Seungjo; Lee, Sang-kwon; Park, Jun-Gyu; Cho, Kyoung-Oh

2018-01-01

Focal vertebral bone density changes were assessed in vertebral computed tomography (CT) images obtained from clinically healthy dogs without diseases that affect bone density. The number, location, and density of lesions were determined. A total of 429 vertebral CT images from 20 dogs were reviewed, and 99 focal vertebral changes were identified in 14 dogs. Focal vertebral bone density changes were mainly found in thoracic vertebrae (29.6%) as hyperattenuating (86.9%) lesions. All focal vertebral changes were observed at the vertebral body, except for a single hyperattenuating change in one thoracic transverse process. Among the hyperattenuating changes, multifocal changes (53.5%) were more common than single changes (46.5%). Most of the hypoattenuating changes were single (92.3%). Eight dogs, 40% of the 20 dogs in the study and 61.6% of the 13 dogs showing focal vertebral changes in the thoracic vertebra, had hyperattenuating changes at the 7th or 8th thoracic vertebra. Our results indicate that focal changes in vertebral bone density are commonly identified on vertebral CT images in healthy dogs, and these changes should be taken into consideration on interpretation of CT images. PMID:28693309

Tissue Motion and Assembly During Early Cardiovascular Morphogenesis

NASA Astrophysics Data System (ADS)

Rongish, Brenda

2010-03-01

Conventional dogma in the field of cardiovascular developmental biology suggests that cardiac precursor cells migrate to the embryonic midline to form a tubular heart. These progenitors are believed to move relative to their extracellular matrix (ECM); responding to stimulatory and inhibitory cues in their environment. The tubular heart that is formed by 30 hours post fertilization is comprised of two concentric layers: the muscular myocardium and the endothelial-like endocardium, which are separated by a thick layer of ECM believed to be secreted predominantly by the myocardial cells. Here we describe the origin and motility of fluorescently tagged endocardial precursors in transgenic (Tie1-YFP) quail embryos (R. Lansford, Caltech) using epifluorescence time-lapse imaging. To visualize the environment of migrating endocardial progenitors, we labeled two ECM components, fibronectin and fibrillin-2, via in vivo microinjection of fluorochrome-conjugated monoclonal antibodies. Dynamic imaging was performed at stages encompassing tubular heart assembly and early looping. We established the motion of endocardial precursor cells and presumptive cardiac ECM fibrils using both object tracking and particle image velocimetry (image cross correlation). We determined the relative importance of directed cell autonomous motility versus passive tissue movements in endocardial morphogenesis. The data show presumptive endocardial cells and cardiac ECM fibrils are swept passively into the anterior and posterior poles of the elongating tubular heart. These quantitative data indicate the contribution of cell autonomous motility displayed by endocardial precursors is limited. Thus, tissue motion drives most of the cell displacements during endocardial morphogenesis.

Metamerism in cephalochordates and the problem of the vertebrate head.

PubMed

Onai, Takayuki; Adachi, Noritaka; Kuratani, Shigeru

2017-01-01

The vertebrate head characteristically exhibits a complex pattern with sense organs, brain, paired eyes and jaw muscles, and the brain case is not found in other chordates. How the extant vertebrate head has evolved remains enigmatic. Historically, there have been two conflicting views on the origin of the vertebrate head, segmental and non-segmental views. According to the segmentalists, the vertebrate head is organized as a metameric structure composed of segments equivalent to those in the trunk; a metamere in the vertebrate head was assumed to consist of a somite, a branchial arch and a set of cranial nerves, considering that the head evolved from rostral segments of amphioxus-like ancestral vertebrates. Non-segmentalists, however, considered that the vertebrate head was not segmental. In that case, the ancestral state of the vertebrate head may be non-segmented, and rostral segments in amphioxus might have been secondarily gained, or extant vertebrates might have evolved through radical modifications of amphioxus-like ancestral vertebrate head. Comparative studies of mesodermal development in amphioxus and vertebrate gastrula embryos have revealed that mesodermal gene expressions become segregated into two domains anteroposteriorly to specify the head mesoderm and trunk mesoderm only in vertebrates; in this segregation, key genes such as delta and hairy, involved in segment formation, are expressed in the trunk mesoderm, but not in the head mesoderm, strongly suggesting that the head mesoderm of extant vertebrates is not segmented. Taken together, the above finding possibly adds a new insight into the origin of the vertebrate head; the vertebrate head mesoderm would have evolved through an anteroposterior polarization of the paraxial mesoderm if the ancestral vertebrate had been amphioxus-like.

Giga-voxel computational morphogenesis for structural design

NASA Astrophysics Data System (ADS)

Aage, Niels; Andreassen, Erik; Lazarov, Boyan S.; Sigmund, Ole

2017-10-01

In the design of industrial products ranging from hearing aids to automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer-aided design approaches. The computer-aided approach known as topology optimization enables unrestricted design freedom and shows great promise with regard to weight savings, but its applicability has so far been limited to the design of single components or simple structures, owing to the resolution limits of current optimization methods. Here we report a computational morphogenesis tool, implemented on a supercomputer, that produces designs with giga-voxel resolution—more than two orders of magnitude higher than previously reported. Such resolution provides insights into the optimal distribution of material within a structure that were hitherto unachievable owing to the challenges of scaling up existing modelling and optimization frameworks. As an example, we apply the tool to the design of the internal structure of a full-scale aeroplane wing. The optimized full-wing design has unprecedented structural detail at length scales ranging from tens of metres to millimetres and, intriguingly, shows remarkable similarity to naturally occurring bone structures in, for example, bird beaks. We estimate that our optimized design corresponds to a reduction in mass of 2-5 per cent compared to currently used aeroplane wing designs, which translates into a reduction in fuel consumption of about 40-200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems, antennas, nano-optics and micro-systems.

Giga-voxel computational morphogenesis for structural design.

PubMed

Aage, Niels; Andreassen, Erik; Lazarov, Boyan S; Sigmund, Ole

2017-10-04

In the design of industrial products ranging from hearing aids to automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer-aided design approaches. The computer-aided approach known as topology optimization enables unrestricted design freedom and shows great promise with regard to weight savings, but its applicability has so far been limited to the design of single components or simple structures, owing to the resolution limits of current optimization methods. Here we report a computational morphogenesis tool, implemented on a supercomputer, that produces designs with giga-voxel resolution-more than two orders of magnitude higher than previously reported. Such resolution provides insights into the optimal distribution of material within a structure that were hitherto unachievable owing to the challenges of scaling up existing modelling and optimization frameworks. As an example, we apply the tool to the design of the internal structure of a full-scale aeroplane wing. The optimized full-wing design has unprecedented structural detail at length scales ranging from tens of metres to millimetres and, intriguingly, shows remarkable similarity to naturally occurring bone structures in, for example, bird beaks. We estimate that our optimized design corresponds to a reduction in mass of 2-5 per cent compared to currently used aeroplane wing designs, which translates into a reduction in fuel consumption of about 40-200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems, antennas, nano-optics and micro-systems.

Vertebral hemangiomas: their demographical characteristics, location along the spine and position within the vertebral body.

PubMed

Slon, Viviane; Stein, Dan; Cohen, Haim; Sella-Tunis, Tatiana; May, Hila; Hershkovitz, Israel

2015-10-01

Vertebral hemangiomas (VHs) are the most common form of benign tumors in the spine. The aim of this research was to study the prevalence of VHs in the human population, their distribution along the spine and their location in the vertebral body. The presence of VHs was assessed in full spine CT scans of 196 adults. Demographic data were gathered from medical records. VHs were present in 26.0% of the individuals studied, a rate significantly higher (χ2=43.338, p<0.001) than the prevalence reported in the literature (10.7%). Multiple VHs (≥2) appeared in 7.2% of the population studied. VHs prevalence is sex-independent, appearing in 28.6% of females and 23.5% of males (χ2=0.663, p=0.416); and age-dependent: the mean age of affected individuals (65.8 years) was significantly higher (p<0.001) than unaffected individuals (56.2 years). VH size was also age-dependent (p=0.023). No vertebra was significantly more prone to be affected by a hemangioma. T11 and T12 show the highest prevalence of VHs (3.57% of vertebrae affected). VHs were found in similar percentages in the anterior and posterior parts of the vertebral body (52.8 vs. 47.2%, respectively); and at its center and periphery (50.1 and 49.9%, respectively). VHs usually appeared at mid-height of the vertebral body or slightly higher. The reported prevalence of VHs is dependent on the demographic structure of the population studied, the size of the VHs and the method used to identify them. Overall, the phenomenon is more frequent than usually reported. VHs may appear at all vertebral levels and in all areas of the vertebral body.

The Petunia GRAS Transcription Factor ATA/RAM1 Regulates Symbiotic Gene Expression and Fungal Morphogenesis in Arbuscular Mycorrhiza.

PubMed

Rich, Mélanie K; Schorderet, Martine; Bapaume, Laure; Falquet, Laurent; Morel, Patrice; Vandenbussche, Michiel; Reinhardt, Didier

2015-07-01

Arbuscular mycorrhiza (AM) is a mutual symbiosis that involves a complex symbiotic interface over which nutrients are exchanged between the plant host and the AM fungus. Dozens of genes in the host are required for the establishment and functioning of the interaction, among them nutrient transporters that mediate the uptake of mineral nutrients delivered by the fungal arbuscules. We have isolated in a genetic mutant screen a petunia (Petunia hybrida) Gibberellic Acid Insensitive, Repressor of Gibberellic Acid Insensitive, and Scarecrow (GRAS)-type transcription factor, Atypical Arbuscule (ATA), that acts as the central regulator of AM-related genes and is required for the morphogenesis of arbuscules. Forced mycorrhizal inoculations from neighboring wild-type plants revealed an additional role of ATA in restricting mycorrhizal colonization of the root meristem. The lack of ATA, which represents the ortholog of Required For Arbuscular Mycorrhiza1 in Medicago truncatula, renders the interaction completely ineffective, hence demonstrating the central role of AM-related genes for arbuscule development and function. © 2015 American Society of Plant Biologists. All Rights Reserved.

An integrated miRNA functional screening and target validation method for organ morphogenesis.

PubMed

Rebustini, Ivan T; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A; Maas, Richard L

2016-03-16

The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

The Expanding Diversity of RNA Viruses in Vertebrates.

PubMed

Wang, Wenqiang; Han, Guan-Zhu

2018-06-01

The diversity of RNA viruses in vertebrates remains largely unexplored. The discovery of 214 novel vertebrate-associated RNA viruses will likely help us to understand the diversity and evolution of RNA viruses in vertebrates. Copyright © 2018 Elsevier Ltd. All rights reserved.

SACE_0012, a TetR-family transcriptional regulator, affects the morphogenesis of Saccharopolyspora erythraea.

PubMed

Yin, Xiaojuan; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

2013-12-01

Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR, the relative transcription of SACE_7115, the amfC homolog for an aerial mycelium formation protein, was dramatically increased in SACE_0012 mutant, whereas erythromycin biosynthetic gene eryA, a pleiotropic regulatory gene bldD, and the genes SACE_2141, SACE_6464, SACE_6040, that are the homologs to the sporulation regulators WhiA, WhiB, WhiG, were not differentially expressed. SACE_0012 disruption could not restore its defect of aerial development in bldD mutant, and also did not further accelerate the mycelium formation in the mutant of SACE_7040 gene, that was previously identified to be a morphogenesis repressor. Furthermore, the transcriptional level of SACE_0012 had not markedly changed in bldD and SACE_7040 mutant over A226. Taken together, these results suggest that SACE_0012 is a negative regulator of S. erythraea morphogenesis by mainly increasing the transcription of amfC gene, independently of the BldD regulatory system.

Morphogenesis and gravity in a whole amphibian embryo and in isolated blastomeres of sea urchins.

PubMed

Izumi-Kurotani, Akemi; Kiyomoto, Masato

2003-01-01

Fertilization and subsequent embryogenesis of newts occurred normally under microgravity in two Astronewt flight experiments. By accumulation of the results from the amphibian flight experiments including 'Astronewt', it is considered that gravity has rather small effects on the early development of amphibian eggs. However, some temporary abnormalities, which recover in the course of the further developmental process, have been observed. Some regulations may occur in whole embryos. For a thorough knowledge about the role of gravity in morphogenesis, we need to investigate the gravitational effects on a single cell in a whole embryo. We propose a new experimental system with sea urchin embryos and micromeres for further studies at a cellular level of the effects of gravity on morphogenesis.

Vestibular blueprint in early vertebrates.

PubMed

Straka, Hans; Baker, Robert

2013-11-19

Central vestibular neurons form identifiable subgroups within the boundaries of classically outlined octavolateral nuclei in primitive vertebrates that are distinct from those processing lateral line, electrosensory, and auditory signals. Each vestibular subgroup exhibits a particular morpho-physiological property that receives origin-specific sensory inputs from semicircular canal and otolith organs. Behaviorally characterized phenotypes send discrete axonal projections to extraocular, spinal, and cerebellar targets including other ipsi- and contralateral vestibular nuclei. The anatomical locations of vestibuloocular and vestibulospinal neurons correlate with genetically defined hindbrain compartments that are well conserved throughout vertebrate evolution though some variability exists in fossil and extant vertebrate species. The different vestibular subgroups exhibit a robust sensorimotor signal processing complemented with a high degree of vestibular and visual adaptive plasticity.

Unusual vertebral artery origins: examples and related pathology.

PubMed

Koenigsberg, Robert A; Pereira, Lorianne; Nair, Bronwyn; McCormick, Daniel; Schwartzman, Robert

2003-06-01

Anomalies of the vertebral arteries are uncommon, but important to recognize in the diagnosis and catheter based evaluation and treatment of patients suffering cerebrovascular disease. This article illustrates our experience with such anomalies. These include the vertebral artery arising as the fourth and most distal branch of the aortic arch, as a right subclavian artery branch arising distal to the right thyrocervical trunk, as a right common carotid artery branch in a patient with an aberrant right subclavian artery, and a case of left vertebral artery proximal duplication, with both aortic and left subclavian vertebral arteries present in the same patient; the latter join to form a single distal cervical vertebral artery. Copyright 2003 Wiley-Liss, Inc.

Effect of teriparatide on pregnancy and lactation-associated osteoporosis with multiple vertebral fractures.

PubMed

Choe, Eun Yeong; Song, Je Eun; Park, Kyeong Hye; Seok, Hannah; Lee, Eun Jig; Lim, Sung-Kil; Rhee, Yumie

2012-09-01

Pregnancy and lactation-associated osteoporosis (PLO) is very rare, but it can cause severe vertebral compression fractures with disabling back pain. PLO patients have commonly been treated with antiresorptive agents against high bone turnover. There are, however, some concerns regarding the use of bisphosphonates: (1) PLO occurs during the first pregnancy with a high possibility of recurrence during the second pregnancy, (2) long-term outcomes of bisphosphonates in PLO are lacking, and (3) there is a possibility of bisphosphonates accumulated in the bones crossing the placenta. Therefore, alternative therapies must be considered. We analyzed the effect of teriparatide (TPTD), the human recombinant parathyroid hormone (1-34), for 18 months in three women with PLO. Multiple vertebral fractures with severe back pain appeared within 6 months after their first childbirth. Two of them had a family history of osteoporosis. Lactation was discontinued immediately after diagnosis of PLO. Calcium carbonate, cholecalciferol, and TPTD were prescribed. The back pain immediately resolved. Bone mineral density (BMD) increased by 14.5-25.0% (mean 19.5%) at the lumbar spine and by 9.5-16.7% (mean 13.1%) at the femoral neck, after 18 months of treatment. The final Z scores in these PLO patients were nearly normalized. Two women had a second baby without any complication. BMD significantly improved after 18 months of treatment with TPTD without further fractures. In conclusion, TPTD should be considered to avoid long-term morbidity in young patients with PLO and is highly encouraged for use in PLO patients with multiple vertebral fractures.

Conjoined twins: morphogenesis of the heart and a review.

PubMed

Gilbert-Barness, Enid; Debich-Spicer, Diane; Opitz, John M

2003-08-01

Five cases of conjoined twins have been studied. These included three thoracopagus twins, one monocephalus diprosopus (prosop = face), and one dicephalus dipus dibrachus. The thoracopagus twins were conjoined only from the upper thorax to the umbilicus with a normal foregut. These three cases shared a single complex multiventricular heart, one with a four chambered heart with one atrium and one ventricle belonging to each twin with complex venous and arterial connection; two had a seven chambered heart with four atria and three ventricles. The mono-cephalus diprosopus twins had a single heart with tetralogy of Fallot. The dicephalus twins had two separate axial skeletons to the sacrum, two separate hearts were connected between the right atria with a shared inferior vena cava. Thoracopagus twinning is associated with complex cardiac malformations. The cardiac anlagen in cephalopagus or diprosopus are diverted and divided along with the entire rostral end of the embryonic disc and result in two relatively normal shared hearts. However, in thoracopagus twins the single heart is multiventricular and suggests very early union with fusion of the cardiac anlagen before significant differentiation. Cardiac morphogenesis in conjoined twins therefore appears to depend on the site of the conjoined fusion and the temporal and spatial influence that determines morphogenesis as well as abnormally oriented embryonic axes. Copyright 2003 Wiley-Liss, Inc.

Evolutionary stasis in pollen morphogenesis due to natural selection.

PubMed

Matamoro-Vidal, Alexis; Prieu, Charlotte; Furness, Carol A; Albert, Béatrice; Gouyon, Pierre-Henri

2016-01-01

The contribution of developmental constraints and selective forces to the determination of evolutionary patterns is an important and unsolved question. We test whether the long-term evolutionary stasis observed for pollen morphogenesis (microsporogenesis) in eudicots is due to developmental constraints or to selection on a morphological trait shaped by microsporogenesis: the equatorial aperture pattern. Most eudicots have three equatorial apertures but several taxa have independently lost the equatorial pattern and have microsporogenesis decoupled from aperture pattern determination. If selection on the equatorial pattern limits variation, we expect to see increased variation in microsporogenesis in the nonequatorial clades. Variation of microsporogenesis was studied using phylogenetic comparative analyses in 83 species dispersed throughout eudicots including species with and without equatorial apertures. The species that have lost the equatorial pattern have highly variable microsporogenesis at the intra-individual and inter-specific levels regardless of their pollen morphology, whereas microsporogenesis remains stable in species with the equatorial pattern. The observed burst of variation upon loss of equatorial apertures shows that there are no strong developmental constraints precluding variation in microsporogenesis, and that the stasis is likely to be due principally to selective pressure acting on pollen morphogenesis because of its implication in the determination of the equatorial aperture pattern. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Mis-expression of grainyhead-like transcription factors in zebrafish leads to defects in enveloping layer (EVL) integrity, cellular morphogenesis and axial extension.

PubMed

Miles, Lee B; Darido, Charbel; Kaslin, Jan; Heath, Joan K; Jane, Stephen M; Dworkin, Sebastian

2017-12-14

The grainyhead-like (grhl) transcription factors play crucial roles in craniofacial development, epithelial morphogenesis, neural tube closure, and dorso-ventral patterning. By utilising the zebrafish to differentially regulate expression of family members grhl2b and grhl3, we show that both genes regulate epithelial migration, particularly convergence-extension (CE) type movements, during embryogenesis. Genetic deletion of grhl3 via CRISPR/Cas9 results in failure to complete epiboly and pre-gastrulation embryonic rupture, whereas morpholino (MO)-mediated knockdown of grhl3 signalling leads to aberrant neural tube morphogenesis at the midbrain-hindbrain boundary (MHB), a phenotype likely due to a compromised overlying enveloping layer (EVL). Further disruptions of grhl3-dependent pathways (through co-knockdown of grhl3 with target genes spec1 and arhgef19) confirm significant MHB morphogenesis and neural tube closure defects. Concomitant MO-mediated disruption of both grhl2b and grhl3 results in further extensive CE-like defects in body patterning, notochord and somite morphogenesis. Interestingly, over-expression of either grhl2b or grhl3 also leads to numerous phenotypes consistent with disrupted cellular migration during gastrulation, including embryo dorsalisation, axial duplication and impaired neural tube migration leading to cyclopia. Taken together, our study ascribes novel roles to the Grhl family in the context of embryonic development and morphogenesis.

Three-dimensional morphogenesis of MDCK cells induced by cellular contractile forces on a viscous substrate

PubMed Central

Imai, Misako; Furusawa, Kazuya; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

2015-01-01

Substrate physical properties are essential for many physiological events such as embryonic development and 3D tissue formation. Physical properties of the extracellular matrix such as viscoelasticity and geometrical constraints are understood as factors that affect cell behaviour. In this study, we focused on the relationship between epithelial cell 3D morphogenesis and the substrate viscosity. We observed that Madin-Darby Canine Kidney (MDCK) cells formed 3D structures on a viscous substrate (Matrigel). The structures appear as a tulip hat. We then changed the substrate viscosity by genipin (GP) treatment. GP is a cross-linker of amino groups. Cells cultured on GP-treated-matrigel changed their 3D morphology in a substrate viscosity-dependent manner. Furthermore, to elucidate the spatial distribution of the cellular contractile force, localization of mono-phosphorylated and di-phosphorylated myosin regulatory light chain (P-MRLCs) was visualized by immunofluorescence. P-MRLCs localized along the periphery of epithelial sheets. Treatment with Y-27632, a Rho-kinase inhibitor, blocked the P-MRLCs localization at the edge of epithelial sheets and halted 3D morphogenesis. Our results indicate that the substrate viscosity, the substrate deformation, and the cellular contractile forces induced by P-MRLCs play crucial roles in 3D morphogenesis. PMID:26374384

The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes

PubMed Central

Di-Poï, Nicolas; Milinkovitch, Michel C.

2016-01-01

Most mammals, birds, and reptiles are readily recognized by their hairs, feathers, and scales, respectively. However, the lack of fossil intermediate forms between scales and hairs and substantial differences in their morphogenesis and protein composition have fueled the controversy pertaining to their potential common ancestry for decades. Central to this debate is the apparent lack of an “anatomical placode” (that is, a local epidermal thickening characteristic of feathers’ and hairs’ early morphogenesis) in reptile scale development. Hence, scenarios have been proposed for the independent development of the anatomical placode in birds and mammals and parallel co-option of similar signaling pathways for their morphogenesis. Using histological and molecular techniques on developmental series of crocodiles and snakes, as well as of unique wild-type and EDA (ectodysplasin A)–deficient scaleless mutant lizards, we show for the first time that reptiles, including crocodiles and squamates, develop all the characteristics of an anatomical placode: columnar cells with reduced proliferation rate, as well as canonical spatial expression of placode and underlying dermal molecular markers. These results reveal a new evolutionary scenario where hairs, feathers, and scales of extant species are homologous structures inherited, with modification, from their shared reptilian ancestor’s skin appendages already characterized by an anatomical placode and associated signaling molecules. PMID:28439533

Three-dimensional morphogenesis of MDCK cells induced by cellular contractile forces on a viscous substrate.

PubMed

Imai, Misako; Furusawa, Kazuya; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

2015-09-16

Substrate physical properties are essential for many physiological events such as embryonic development and 3D tissue formation. Physical properties of the extracellular matrix such as viscoelasticity and geometrical constraints are understood as factors that affect cell behaviour. In this study, we focused on the relationship between epithelial cell 3D morphogenesis and the substrate viscosity. We observed that Madin-Darby Canine Kidney (MDCK) cells formed 3D structures on a viscous substrate (Matrigel). The structures appear as a tulip hat. We then changed the substrate viscosity by genipin (GP) treatment. GP is a cross-linker of amino groups. Cells cultured on GP-treated-matrigel changed their 3D morphology in a substrate viscosity-dependent manner. Furthermore, to elucidate the spatial distribution of the cellular contractile force, localization of mono-phosphorylated and di-phosphorylated myosin regulatory light chain (P-MRLCs) was visualized by immunofluorescence. P-MRLCs localized along the periphery of epithelial sheets. Treatment with Y-27632, a Rho-kinase inhibitor, blocked the P-MRLCs localization at the edge of epithelial sheets and halted 3D morphogenesis. Our results indicate that the substrate viscosity, the substrate deformation, and the cellular contractile forces induced by P-MRLCs play crucial roles in 3D morphogenesis.

The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes.

PubMed

Di-Poï, Nicolas; Milinkovitch, Michel C

2016-06-01

Most mammals, birds, and reptiles are readily recognized by their hairs, feathers, and scales, respectively. However, the lack of fossil intermediate forms between scales and hairs and substantial differences in their morphogenesis and protein composition have fueled the controversy pertaining to their potential common ancestry for decades. Central to this debate is the apparent lack of an "anatomical placode" (that is, a local epidermal thickening characteristic of feathers' and hairs' early morphogenesis) in reptile scale development. Hence, scenarios have been proposed for the independent development of the anatomical placode in birds and mammals and parallel co-option of similar signaling pathways for their morphogenesis. Using histological and molecular techniques on developmental series of crocodiles and snakes, as well as of unique wild-type and EDA (ectodysplasin A)-deficient scaleless mutant lizards, we show for the first time that reptiles, including crocodiles and squamates, develop all the characteristics of an anatomical placode: columnar cells with reduced proliferation rate, as well as canonical spatial expression of placode and underlying dermal molecular markers. These results reveal a new evolutionary scenario where hairs, feathers, and scales of extant species are homologous structures inherited, with modification, from their shared reptilian ancestor's skin appendages already characterized by an anatomical placode and associated signaling molecules.

A Case of Duplicated Right Vertebral Artery.

PubMed

Motomura, Mayuko; Watanabe, Koichi; Tabira, Yoko; Iwanaga, Joe; Matsuuchi, Wakako; Yoshida, Daichi; Saga, Tsuyoshi; Yamaki, Koh-Ichi

2018-04-27

We encountered a case of duplicated right vertebral artery during an anatomical dissection course for medical students in 2015. Two vertebral arteries were found in the right neck of a 91-year-old female cadaver. The proximal leg of the arteries arose from the area between the right subclavian artery and the right common carotid artery that diverged from the brachiocephalic artery. The distal leg arose from the right subclavian artery as expected. The proximal leg entered the transverse foramen of the fourth cervical vertebra and the distal leg entered the transverse foramen of the sixth cervical vertebra. The two right vertebral arteries joined to form one artery just after the origin of the right vertebral artery of the brachiocephalic artery entered the transverse foramen of the fourth cervical vertebra. This artery then traveled up in the transverse foramina and became the basilar artery, joining with the left vertebral artery. We discuss the embryological origin of this case and review previously reported cases.

hmmr mediates anterior neural tube closure and morphogenesis in the frog Xenopus.

PubMed

Prager, Angela; Hagenlocher, Cathrin; Ott, Tim; Schambony, Alexandra; Feistel, Kerstin

2017-10-01

Development of the central nervous system requires orchestration of morphogenetic processes which drive elevation and apposition of the neural folds and their fusion into a neural tube. The newly formed tube gives rise to the brain in anterior regions and continues to develop into the spinal cord posteriorly. Conspicuous differences between the anterior and posterior neural tube become visible already during neural tube closure (NTC). Planar cell polarity (PCP)-mediated convergent extension (CE) movements are restricted to the posterior neural plate, i.e. hindbrain and spinal cord, where they propagate neural fold apposition. The lack of CE in the anterior neural plate correlates with a much slower mode of neural fold apposition anteriorly. The morphogenetic processes driving anterior NTC have not been addressed in detail. Here, we report a novel role for the breast cancer susceptibility gene and microtubule (MT) binding protein Hmmr (Hyaluronan-mediated motility receptor, RHAMM) in anterior neurulation and forebrain development in Xenopus laevis. Loss of hmmr function resulted in a lack of telencephalic hemisphere separation, arising from defective roof plate formation, which in turn was caused by impaired neural tissue narrowing. hmmr regulated polarization of neural cells, a function which was dependent on the MT binding domains. hmmr cooperated with the core PCP component vangl2 in regulating cell polarity and neural morphogenesis. Disrupted cell polarization and elongation in hmmr and vangl2 morphants prevented radial intercalation (RI), a cell behavior essential for neural morphogenesis. Our results pinpoint a novel role of hmmr in anterior neural development and support the notion that RI is a major driving force for anterior neurulation and forebrain morphogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Regulation of lung branching morphogenesis by bombesin-like peptides and neutral endopeptidase.

PubMed

Aguayo, S M; Schuyler, W E; Murtagh, J J; Roman, J

1994-06-01

The expression of bombesin-like peptides (BLPs) by pulmonary neuroendocrine cells is transiently upregulated during lung development. A functional role for BLPs is supported by their ability to stimulate lung growth and maturation both in vitro and in vivo during the late stages of lung development. In addition, the cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP), which inactivates BLPs and other regulatory peptides, is also expressed by developing lungs and modulates the stimulatory effects of BLPs on lung growth and maturation. We hypothesized that, in addition to expressing BLPs and CD10/NEP, embryonic lungs must express BLP receptors, and that BLPs may also regulate processes that occur during early lung development such as branching morphogenesis. Using reverse transcriptase-polymerase chain reaction and oligonucleotide primers designed for amplifying a BLP receptor originally isolated from Swiss 3T3 mouse fibroblasts, we found that embryonic mouse lungs express a similar BLP receptor mRNA during the pseudoglandular stage of lung development when branching morphogenesis take place. Subsequently, we evaluated the effects of ligands for this BLP receptor using embryonic mouse lungs in an in vitro model of lung branching morphogenesis. We found that, in comparison with control lungs, treatment with bombesin (1 to 100 nM) resulted in a modest increase in clefts or branching points. In contrast, embryonic mouse lungs treated with the BLP analog [Leu13-psi(CH2NH)Leu14]bombesin (1 microM), which also binds to this BLP receptor but has predominantly antagonistic effects, demonstrated fewer branching points.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of Sproutys and SPREDs is decreased during lung branching morphogenesis in nitrofen-induced pulmonary hypoplasia.

PubMed

Friedmacher, Florian; Gosemann, Jan-Hendrik; Fujiwara, Naho; Takahashi, Hiromizu; Hofmann, Alejandro; Puri, Prem

2013-11-01

Pulmonary hypoplasia (PH) is a life-threatening condition associated with congenital diaphragmatic hernia (CDH), characterized by defective lung development. Sproutys and Sprouty-related proteins (SPREDs) play a key role in lung branching morphogenesis through modification of epithelial-mesenchymal interactions. During the pseudoglandular stage, Sproutys are highly expressed in distal airway epithelium, while SPREDs within the surrounding mesenchyme. Sprouty2/4 knockouts show severe defects in branching morphogenesis with reduced number of distal airways. SPRED-1 and SPRED-2 are strongly expressed in regions of new airway formation, highlighting their important function in branching pattern. We hypothesized that expression of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 is decreased during lung branching morphogenesis in nitrofen-induced PH. Timed-pregnant rats received either nitrofen or vehicle on E9.5. On E15.5 (n = 16), fetal lungs were micro-dissected and divided into controls and PH, while on E18.5 (n = 24) groups were: control, PH without CDH [CDH(-)], and PH with CDH [CDH(+)]. Pulmonary gene expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were analyzed by qRT-PCR. Immunohistochemistry was performed to evaluate protein expression/distribution. On E18.5, relative mRNA expression levels of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 were significantly decreased in CDH(-) and CDH(+) groups compared to controls (P < 0.05). Immunoreactivity of Sprouty2, Sprouty4, SPRED-1 and SPRED-2 was markedly diminished on E18.5 in nitrofen-induced PH. Decreased expression of Sproutys and SPREDs during the terminal pseudoglandular stage may disrupt lung branching morphogenesis by interfering with epithelial-mesenchymal interactions contributing to PH.

Innate immunity in vertebrates: an overview.

PubMed

Riera Romo, Mario; Pérez-Martínez, Dayana; Castillo Ferrer, Camila

2016-06-01

Innate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation. © 2016 John Wiley & Sons Ltd.

Finite Element Analysis of Denosumab Treatment Effects on Vertebral Strength in Ovariectomized Cynomolgus Monkeys.

PubMed

Lee, David C; Varela, Aurore; Kostenuik, Paul J; Ominsky, Michael S; Keaveny, Tony M

2016-08-01

Finite element analysis has not yet been validated for measuring changes in whole-bone strength at the hip or spine in people after treatment with an osteoporosis agent. Toward that end, we assessed the ability of a clinically approved implementation of finite element analysis to correctly quantify treatment effects on vertebral strength, comparing against direct mechanical testing, in cynomolgus monkeys randomly assigned to one of three 16-month-long treatments: sham surgery with vehicle (Sham-Vehicle), ovariectomy with vehicle (OVX-Vehicle), or ovariectomy with denosumab (OVX-DMAb). After treatment, T12 vertebrae were retrieved, scanned with micro-CT, and mechanically tested to measure compressive strength. Blinded to the strength data and treatment codes, the micro-CT images were coarsened and homogenized to create continuum-type finite element models, without explicit porosity. With clinical translation in mind, these models were then analyzed for strength using the U.S. Food and Drug Administration (FDA)-cleared VirtuOst software application (O.N. Diagnostics, Berkeley, CA, USA), developed for analysis of human bones. We found that vertebral strength by finite element analysis was highly correlated (R(2)  = 0.97; n = 52) with mechanical testing, independent of treatment (p = 0.12). Further, the size of the treatment effect on strength (ratio of mean OVX-DMAb to mean OVX-Vehicle, as a percentage) was large and did not differ (p = 0.79) between mechanical testing (+57%; 95% CI [26%, 95%]) and finite element analysis (+51% [20%, 88%]). The micro-CT analysis revealed increases in cortical thickness (+45% [19%, 73%]) and trabecular bone volume fraction (+24% [8%, 42%]). These results show that a preestablished clinical finite element analysis implementation-developed for human bone and clinically validated in fracture-outcome studies-correctly quantified the observed treatment effects of denosumab on vertebral strength in cynomolgus monkeys. One

The evolution of early vertebrate photoreceptors.

PubMed

Collin, Shaun P; Davies, Wayne L; Hart, Nathan S; Hunt, David M

2009-10-12

Meeting the challenge of sampling an ancient aquatic landscape by the early vertebrates was crucial to their survival and would establish a retinal bauplan to be used by all subsequent vertebrate descendents. Image-forming eyes were under tremendous selection pressure and the ability to identify suitable prey and detect potential predators was thought to be one of the major drivers of speciation in the Early Cambrian. Based on the fossil record, we know that hagfishes, lampreys, holocephalans, elasmobranchs and lungfishes occupy critical stages in vertebrate evolution, having remained relatively unchanged over hundreds of millions of years. Now using extant representatives of these 'living fossils', we are able to piece together the evolution of vertebrate photoreception. While photoreception in hagfishes appears to be based on light detection and controlling circadian rhythms, rather than image formation, the photoreceptors of lampreys fall into five distinct classes and represent a critical stage in the dichotomy of rods and cones. At least four types of retinal cones sample the visual environment in lampreys mediating photopic (and potentially colour) vision, a sampling strategy retained by lungfishes, some modern teleosts, reptiles and birds. Trichromacy is retained in cartilaginous fishes (at least in batoids and holocephalans), where it is predicted that true scotopic (dim light) vision evolved in the common ancestor of all living gnathostomes. The capacity to discriminate colour and balance the tradeoff between resolution and sensitivity in the early vertebrates was an important driver of eye evolution, where many of the ocular features evolved were retained as vertebrates progressed on to land.

Correlation between Hox code and vertebral morphology in archosaurs.

PubMed

Böhmer, Christine; Rauhut, Oliver W M; Wörheide, Gert

2015-07-07

The relationship between developmental genes and phenotypic variation is of central interest in evolutionary biology. An excellent example is the role of Hox genes in the anteroposterior regionalization of the vertebral column in vertebrates. Archosaurs (crocodiles, dinosaurs including birds) are highly variable both in vertebral morphology and number. Nevertheless, functionally equivalent Hox genes are active in the axial skeleton during embryonic development, indicating that the morphological variation across taxa is likely owing to modifications in the pattern of Hox gene expression. By using geometric morphometrics, we demonstrate a correlation between vertebral Hox code and quantifiable vertebral morphology in modern archosaurs, in which the boundaries between morphological subgroups of vertebrae can be linked to anterior Hox gene expression boundaries. Our findings reveal homologous units of cervical vertebrae in modern archosaurs, each with their specific Hox gene pattern, enabling us to trace these homologies in the extinct sauropodomorph dinosaurs, a group with highly variable vertebral counts. Based on the quantifiable vertebral morphology, this allows us to infer the underlying genetic mechanisms in vertebral evolution in fossils, which represents not only an important case study, but will lead to a better understanding of the origin of morphological disparity in recent archosaur vertebral columns.

Correlation between Hox code and vertebral morphology in archosaurs

PubMed Central

Böhmer, Christine; Rauhut, Oliver W. M.; Wörheide, Gert

2015-01-01

The relationship between developmental genes and phenotypic variation is of central interest in evolutionary biology. An excellent example is the role of Hox genes in the anteroposterior regionalization of the vertebral column in vertebrates. Archosaurs (crocodiles, dinosaurs including birds) are highly variable both in vertebral morphology and number. Nevertheless, functionally equivalent Hox genes are active in the axial skeleton during embryonic development, indicating that the morphological variation across taxa is likely owing to modifications in the pattern of Hox gene expression. By using geometric morphometrics, we demonstrate a correlation between vertebral Hox code and quantifiable vertebral morphology in modern archosaurs, in which the boundaries between morphological subgroups of vertebrae can be linked to anterior Hox gene expression boundaries. Our findings reveal homologous units of cervical vertebrae in modern archosaurs, each with their specific Hox gene pattern, enabling us to trace these homologies in the extinct sauropodomorph dinosaurs, a group with highly variable vertebral counts. Based on the quantifiable vertebral morphology, this allows us to infer the underlying genetic mechanisms in vertebral evolution in fossils, which represents not only an important case study, but will lead to a better understanding of the origin of morphological disparity in recent archosaur vertebral columns. PMID:26085583

Autophagy in osteoblasts is involved in mineralization and bone homeostasis

PubMed Central

Nollet, Marie; Santucci-Darmanin, Sabine; Breuil, Véronique; Al-Sahlanee, Rasha; Cros, Chantal; Topi, Majlinda; Momier, David; Samson, Michel; Pagnotta, Sophie; Cailleteau, Laurence; Battaglia, Séverine; Farlay, Delphine; Dacquin, Romain; Barois, Nicolas; Jurdic, Pierre; Boivin, Georges; Heymann, Dominique; Lafont, Frank; Lu, Shi Shou; Dempster, David W; Carle, Georges F; Pierrefite-Carle, Valérie

2014-01-01

Bone remodeling is a tightly controlled mechanism in which osteoblasts (OB), the cells responsible for bone formation, osteoclasts (OC), the cells specialized for bone resorption, and osteocytes, the multifunctional mechanosensing cells embedded in the bone matrix, are the main actors. Increased oxidative stress in OB, the cells producing and mineralizing bone matrix, has been associated with osteoporosis development but the role of autophagy in OB has not yet been addressed. This is the goal of the present study. We first show that the autophagic process is induced in OB during mineralization. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralization capacity. Moreover, our data suggest that autophagic vacuoles could be used as vehicles in OB to secrete apatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and secretion of the receptor activator of NFKB1 (TNFSF11/RANKL), favoring generation of OC, the cells specialized in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralization process and in bone homeostasis. These findings are of importance for mineralized tissues which extend from corals to vertebrates and uncover new therapeutic targets for calcified tissue-related metabolic pathologies. PMID:25484092

Identification of a new mineralized tissue in the notochord of reared Siberian sturgeon (Acipenser baerii).

PubMed

Leprévost, Amandine; Azaïs, Thierry; Trichet, Michael; Sire, Jean-Yves

2017-11-01

In a study aiming to improve knowledge on the mineralization of the axial skeleton in reared Siberian sturgeon (Acipenser baerii Brandt, 1869), we discovered a new mineralized tissue within the notochord. To our knowledge, such a structure has never been reported in any vertebrate species with the exception of the pathological mineralization of the notochord remains in degenerative intervertebral disks of mammals. Here, we describe this enigmatic tissue using X-ray microtomography, histological analyses and solid state NMR-spectroscopy. We also performed a 1-year monitoring of the mineral content (MC) of the notochord in relation with seasonal variations of temperature. In all specimens studied from 2-year-old juveniles onwards, this mineralized structure was found within a particular region of the notochord called funiculus. This feature first appears in the abdominal region then extends posteriorly with ageing, while the notochord MC also increases. The mineral phase is mainly composed of amorphous calcium phosphate, a small amount of which changes into hydroxyapatite with ageing. The putative role of this structure is discussed as either a store of minerals available for the phosphocalcic metabolism, or a mechanical support in a species with a poorly mineralized axial skeleton. A pathological feature putatively related to rearing conditions is also discussed. © 2017 Wiley Periodicals, Inc.

Constrained vertebrate evolution by pleiotropic genes.

PubMed

Hu, Haiyang; Uesaka, Masahiro; Guo, Song; Shimai, Kotaro; Lu, Tsai-Ming; Li, Fang; Fujimoto, Satoko; Ishikawa, Masato; Liu, Shiping; Sasagawa, Yohei; Zhang, Guojie; Kuratani, Shigeru; Yu, Jr-Kai; Kusakabe, Takehiro G; Khaitovich, Philipp; Irie, Naoki

2017-11-01

Despite morphological diversification of chordates over 550 million years of evolution, their shared basic anatomical pattern (or 'bodyplan') remains conserved by unknown mechanisms. The developmental hourglass model attributes this to phylum-wide conserved, constrained organogenesis stages that pattern the bodyplan (the phylotype hypothesis); however, there has been no quantitative testing of this idea with a phylum-wide comparison of species. Here, based on data from early-to-late embryonic transcriptomes collected from eight chordates, we suggest that the phylotype hypothesis would be better applied to vertebrates than chordates. Furthermore, we found that vertebrates' conserved mid-embryonic developmental programmes are intensively recruited to other developmental processes, and the degree of the recruitment positively correlates with their evolutionary conservation and essentiality for normal development. Thus, we propose that the intensively recruited genetic system during vertebrates' organogenesis period imposed constraints on its diversification through pleiotropic constraints, which ultimately led to the common anatomical pattern observed in vertebrates.

Origin and evolution of the integumentary skeleton in non-tetrapod vertebrates

PubMed Central

Sire, Jean-Yves; Donoghue, Philip C J; Vickaryous, Matthews K

2009-01-01

Most non-tetrapod vertebrates develop mineralized extra-oral elements within the integument. Known collectively as the integumentary skeleton, these elements represent the structurally diverse skin-bound contribution to the dermal skeleton. In this review we begin by summarizing what is known about the histological diversity of the four main groups of integumentary skeletal tissues: hypermineralized (capping) tissues; dentine; plywood-like tissues; and bone. For most modern taxa, the integumentary skeleton has undergone widespread reduction and modification often rendering the homology and relationships of these elements confused and uncertain. Fundamentally, however, all integumentary skeletal elements are derived (alone or in combination) from only two types of cell condensations: odontogenic and osteogenic condensations. We review the origin and diversification of the integumentary skeleton in aquatic non-tetrapods (including stem gnathostomes), focusing on tissues derived from odontogenic (hypermineralized tissues, dentines and elasmodine) and osteogenic (bone tissues) cell condensations. The novelty of our new scenario of integumentary skeletal evolution resides in the demonstration that elasmodine, the main component of elasmoid scales, is odontogenic in origin. Based on available data we propose that elasmodine is a form of lamellar dentine. Given its widespread distribution in non-tetrapod lineages we further propose that elasmodine is a very ancient tissue in vertebrates and predict that it will be found in ancestral rhombic scales and cosmoid scales. PMID:19422423

Mechanical influences in bacterial morphogenesis and cell division

NASA Astrophysics Data System (ADS)

Sun, Sean

2010-03-01

Bacterial cells utilize a ring-like organelle (the Z-ring) to accomplish cell division. The Z-ring actively generates a contractile force and influences cell wall growth. We will discuss a general model of bacterial morphogenesis where mechanical forces are coupled to the growth dynamics of the cell wall. The model suggests a physical mechanism that determines the shapes of bacteria cells. The roles of several bacterial cytoskeletal proteins and the Z-ring are discussed. We will also explore molecular mechanisms of force generation by the Z-ring and how cells can generate mechanical forces without molecular motors.

Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus

PubMed Central

Oei, Ling; Estrada, Karol; Duncan, Emma L.; Christiansen, Claus; Liu, Ching-Ti; Langdahl, Bente L.; Obermayer-Pietsch, Barbara; Riancho, José A.; Prince, Richard L.; van Schoor, Natasja M.; McCloskey, Eugene; Hsu, Yi-Hsiang; Evangelou, Evangelos; Ntzani, Evangelia; Evans, David M.; Alonso, Nerea; Husted, Lise B.; Valero, Carmen; Hernandez, Jose L.; Lewis, Joshua R.; Kaptoge, Stephen K.; Zhu, Kun; Cupples, L. Adrienne; Medina-Gómez, Carolina; Vandenput, Liesbeth; Kim, Ghi Su; Lee, Seung Hun; Castaño-Betancourt, Martha C.; Oei, Edwin H.G.; Martinez, Josefina; Daroszewska, Anna; van der Klift, Marjolein; Mellström, Dan; Herrera, Lizbeth; Karlsson, Magnus K.; Hofman, Albert; Ljunggren, Östen; Pols, Huibert A.P.; Stolk, Lisette; van Meurs, Joyce B.J.; Ioannidis, John P.A.; Zillikens, M. Carola; Lips, Paul; Karasik, David; Uitterlinden, André G.; Styrkarsdottir, Unnur; Brown, Matthew A.; Koh, Jung-Min; Richards, J. Brent; Reeve, Jonathan; Ohlsson, Claes; Ralston, Stuart H.; Kiel, Douglas P.; Rivadeneira, Fernando

2014-01-01

Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fractures applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey–Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey–Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han–Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p < 5 × 10−8. In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p=4.6×10−8. However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% CI: 0.98–1.14; p = 0.17), displaying high degree of heterogeneity (I2=57%; Qhet p =0.0006). Under Han–Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is

Mechanical Contributions of the Cortical and Trabecular Compartments Contribute to Differences in Age-Related Changes in Vertebral Body Strength in Men and Women Assessed by QCT-Based Finite Element Analysis

PubMed Central

Christiansen, Blaine A; Kopperdahl, David L; Kiel, Douglas P; Keaveny, Tony M; Bouxsein, Mary L

2011-01-01

The biomechanical mechanisms underlying sex-specific differences in age-related vertebral fracture rates are ill defined. To gain insight into this issue, we used finite element analysis of clinical computed tomography (CT) scans of the vertebral bodies of L3 and T10 of young and old men and women to assess age- and sex-related differences in the strength of the whole vertebra, the trabecular compartment, and the peripheral compartment (the outer 2 mm of vertebral bone, including the thin cortical shell). We sought to determine whether structural and geometric changes with age differ in men and women, making women more susceptible to vertebral fractures. As expected, we found that vertebral strength decreased with age 2-fold more in women than in men. The strength of the trabecular compartment declined significantly with age for both sexes, whereas the strength of the peripheral compartment decreased with age in women but was largely maintained in men. The proportion of mechanical strength attributable to the peripheral compartment increased with age in both sexes and at both vertebral levels. Taken together, these results indicate that men and women lose vertebral bone differently with age, particularly in the peripheral (cortical) compartment. This differential bone loss explains, in part, a greater decline in bone strength in women and may contribute to the higher incidence of vertebral fractures among women than men. © 2011 American Society for Bone and Mineral Research. PMID:21542000

Laser capture microdissection to study flower morphogenesis

NASA Astrophysics Data System (ADS)

Pawełkowicz, Magdalena Ewa; Skarzyńska, Agnieszka; Kowalczuk, Cezary; PlÄ der, Wojciech; Przybecki, Zbigniew

2017-08-01

Laser Capture Microdissection (LCM) is a sample preparation microscopic method that enables isolation of an interesting cell or cells population from human, animal or plant tissue. This technique allows for obtaining pure sample from heterogeneous mixture. From isolated cells, it is possible to obtain the appropriate quality material used for genomic research in transcriptomics, proteomics and metabolomics. We used LCM method to study flower morphogenesis and specific bud's organ organization and development. The genes expression level in developing flower buds of male (B10) and female (2gg) lines were analyzed with qPCR. The expression was checked for stamen and carpel primordia obtained with LCM and for whole flower buds at successive stages of growth.

Evolutionary Specialization of Tactile Perception in Vertebrates.

PubMed

Schneider, Eve R; Gracheva, Elena O; Bagriantsev, Slav N

2016-05-01

Evolution has endowed vertebrates with the remarkable tactile ability to explore the world through the perception of physical force. Yet the sense of touch remains one of the least well understood senses at the cellular and molecular level. Vertebrates specializing in tactile perception can highlight general principles of mechanotransduction. Here, we review cellular and molecular adaptations that underlie the sense of touch in typical and acutely mechanosensitive vertebrates. ©2016 Int. Union Physiol. Sci./Am. Physiol. Soc.

Facultative parthenogenesis in vertebrates: reproductive error or chance?

PubMed

Lampert, K P

2008-01-01

Parthenogenesis, the development of an embryo from a female gamete without any contribution of a male gamete, is very rare in vertebrates. Parthenogenetically reproducing species have, so far, only been found in the Squamate reptiles (lizards and snakes). Facultative parthenogenesis, switching between sexual and clonal reproduction, although quite common in invertebrates, e.g. Daphnia and aphids, seems to be even rarer in vertebrates. However, isolated cases of parthenogenetic development have been reported in all vertebrate groups. Facultative parthenogenesis in vertebrates has only been found in captive animals but might simply have been overlooked in natural populations. Even though its evolutionary impact is hard to determine and very likely varies depending on the ploidy restoration mechanisms and sex-determining mechanisms involved, facultative parthenogenesis is already discussed in conservation biology and medical research. To raise interest for facultative parthenogenesis especially in evolutionary biology, I summarize the current knowledge about facultative parthenogenesis in the different vertebrate groups, introduce mechanisms of diploid oocyte formation and discuss the genetic consequences and potential evolutionary impact of facultative parthenogenesis in vertebrates.

Ancient deuterostome origins of vertebrate brain signalling centres.

PubMed

Pani, Ariel M; Mullarkey, Erin E; Aronowicz, Jochanan; Assimacopoulos, Stavroula; Grove, Elizabeth A; Lowe, Christopher J

2012-03-14

Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centres-the anterior neural ridge, zona limitans intrathalamica and isthmic organizer-are present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates. © 2012 Macmillan Publishers Limited. All rights reserved

The prevalence of radiographic vertebral fractures in Latin American countries: the Latin American Vertebral Osteoporosis Study (LAVOS).

PubMed

Clark, P; Cons-Molina, F; Deleze, M; Ragi, S; Haddock, L; Zanchetta, J R; Jaller, J J; Palermo, L; Talavera, J O; Messina, D O; Morales-Torres, J; Salmeron, J; Navarrete, A; Suarez, E; Pérez, C M; Cummings, S R

2009-02-01

In the first population-based study of vertebral fractures in Latin America, we found a 11.18 (95% CI 9.23-13.4) prevalence of radiographically ascertained vertebral fractures in a random sample of 1,922 women from cities within five different countries. These figures are similar to findings from studies in Beijing, China, some regions of Europe, and slightly lower than those found in the USA using the same standardized methodology. We report the first study of radiographic vertebral fractures in Latin America. An age-stratified random sample of 1,922 women aged 50 years and older from Argentina, Brazil, Colombia, Mexico, and Puerto Rico were included. In all cases a standardized questionnaire and lateral X-rays of the lumbar and thoracic spine were obtained after informed consent. A standardized prevalence of 11.18 (95% CI 9.23-13.4) was found. The prevalence was similar in all five countries, increasing from 6.9% (95% CI 4.6-9.1) in women aged 50-59 years to 27.8% (95% CI 23.1-32.4) in those 80 years and older (p for trend < 0.001). Among different risk factors, self-reported height loss OR = 1.63 (95% CI: 1.18-2.25), and previous history of fracture OR = 1.52 (95% CI: 1.14-2.03) were significantly (p < 0.003 and p < 0.04 respectably) associated with the presence of radiographic vertebral fractures in the multivariate analysis. In the bivariate analyses HRT was associated with a 35% lower risk OR = 0.65 (95% CI: 0.46-0.93) and physical activity with a 27% lower risk of having a vertebral fracture OR = 0.73 (95% CI: 0.55-0.98), but were not statistically significant in multivariate analyses We conclude that radiographically ascertained vertebral fractures are common in Latin America. Health authorities in the region should be aware and consider implementing measures to prevent vertebral fractures.

Evolution and development of the vertebrate neck

PubMed Central

Ericsson, Rolf; Knight, Robert; Johanson, Zerina

2013-01-01

Muscles of the vertebrate neck include the cucullaris and hypobranchials. Although a functional neck first evolved in the lobe-finned fishes (Sarcopterygii) with the separation of the pectoral/shoulder girdle from the skull, the neck muscles themselves have a much earlier origin among the vertebrates. For example, lampreys possess hypobranchial muscles, and may also possess the cucullaris. Recent research in chick has established that these two muscles groups have different origins, the hypobranchial muscles having a somitic origin but the cucullaris muscle deriving from anterior lateral plate mesoderm associated with somites 1–3. Additionally, the cucullaris utilizes genetic pathways more similar to the head than the trunk musculature. Although the latter results are from experiments in the chick, cucullaris homologues occur in a variety of more basal vertebrates such as the sharks and zebrafish. Data are urgently needed from these taxa to determine whether the cucullaris in these groups also derives from lateral plate mesoderm or from the anterior somites, and whether the former or the latter represent the basal vertebrate condition. Other lateral plate mesoderm derivatives include the appendicular skeleton (fins, limbs and supporting girdles). If the cucullaris is a definitive lateral plate-derived structure it may have evolved in conjunction with the shoulder/limb skeleton in vertebrates and thereby provided a greater degree of flexibility to the heads of predatory vertebrates. PMID:22697305

The Variety of Vertebrate Mechanisms of Sex Determination

PubMed Central

Trukhina, Antonina V.; Lukina, Natalia A.; Wackerow-Kouzova, Natalia D.; Smirnov, Alexander F.

2013-01-01

The review deals with features of sex determination in vertebrates. The mechanisms of sex determination are compared between fishes, amphibians, reptilians, birds, and mammals. We focus on structural and functional differences in the role of sex-determining genes in different vertebrates. Special attention is paid to the role of estrogens in sex determination in nonmammalian vertebrates. PMID:24369014

The variety of vertebrate mechanisms of sex determination.

PubMed

Trukhina, Antonina V; Lukina, Natalia A; Wackerow-Kouzova, Natalia D; Smirnov, Alexander F

2013-01-01

The review deals with features of sex determination in vertebrates. The mechanisms of sex determination are compared between fishes, amphibians, reptilians, birds, and mammals. We focus on structural and functional differences in the role of sex-determining genes in different vertebrates. Special attention is paid to the role of estrogens in sex determination in nonmammalian vertebrates.

Surgical treatment of hematogenous vertebral Aspergillus osteomyelitis.

PubMed

Bridwell, K H; Campbell, J W; Barenkamp, S J

1990-04-01

Three cases of Aspergillus fumigatas vertebral osteomyelitis failed courses of medical treatment. Each was subsequently treated with anterior vertebral debridement and posterior segmental spinal instrumentation. Despite poor nutritional and immune systems, resolution of the infection and subsequent anterior ankylosis occurred in each patient, with follow-up ranging from 1 to 3 years. If patients with aspergillus vertebral osteomyelitis do not respond to medical treatment, early surgical debridement and stabilization in combination with intravenous amphotericin B can lead to resolution and bony ankylosis.

JunB is required for endothelial cell morphogenesis by regulating core-binding factor β

PubMed Central

Licht, Alexander H.; Pein, Oliver T.; Florin, Lore; Hartenstein, Bettina; Reuter, Hendrik; Arnold, Bernd; Lichter, Peter; Angel, Peter; Schorpp-Kistner, Marina

2006-01-01

The molecular mechanism triggering the organization of endothelial cells (ECs) in multicellular tubules is mechanistically still poorly understood. We demonstrate that cell-autonomous endothelial functions of the AP-1 subunit JunB are required for proper endothelial morphogenesis both in vivo in mouse embryos with endothelial-specific ablation of JunB and in in vitro angiogenesis models. By cDNA microarray analysis, we identified core-binding factor β (CBFβ), which together with the Runx proteins forms the heterodimeric core-binding transcription complex CBF, as a novel JunB target gene. In line with our findings, expression of the CBF target MMP-13 was impaired in JunB-deficient ECs. Reintroduction of CBFβ into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFβ in EC morphogenesis. PMID:17158955

Micro/nano-computed tomography technology for quantitative dynamic, multi-scale imaging of morphogenesis.

PubMed

Gregg, Chelsea L; Recknagel, Andrew K; Butcher, Jonathan T

2015-01-01

Tissue morphogenesis and embryonic development are dynamic events challenging to quantify, especially considering the intricate events that happen simultaneously in different locations and time. Micro- and more recently nano-computed tomography (micro/nanoCT) has been used for the past 15 years to characterize large 3D fields of tortuous geometries at high spatial resolution. We and others have advanced micro/nanoCT imaging strategies for quantifying tissue- and organ-level fate changes throughout morphogenesis. Exogenous soft tissue contrast media enables visualization of vascular lumens and tissues via extravasation. Furthermore, the emergence of antigen-specific tissue contrast enables direct quantitative visualization of protein and mRNA expression. Micro-CT X-ray doses appear to be non-embryotoxic, enabling longitudinal imaging studies in live embryos. In this chapter we present established soft tissue contrast protocols for obtaining high-quality micro/nanoCT images and the image processing techniques useful for quantifying anatomical and physiological information from the data sets.

Fully automated bone mineral density assessment from low-dose chest CT

NASA Astrophysics Data System (ADS)

Liu, Shuang; Gonzalez, Jessica; Zulueta, Javier; de-Torres, Juan P.; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

2018-02-01

A fully automated system is presented for bone mineral density (BMD) assessment from low-dose chest CT (LDCT). BMD assessment is central in the diagnosis and follow-up therapy monitoring of osteoporosis, which is characterized by low bone density and is estimated to affect 12.3 million US population aged 50 years or older, creating tremendous social and economic burdens. BMD assessment from DXA scans (BMDDXA) is currently the most widely used and gold standard technique for the diagnosis of osteoporosis and bone fracture risk estimation. With the recent large-scale implementation of annual lung cancer screening using LDCT, great potential emerges for the concurrent opportunistic osteoporosis screening. In the presented BMDCT assessment system, each vertebral body is first segmented and labeled with its anatomical name. Various 3D region of interest (ROI) inside the vertebral body are then explored for BMDCT measurements at different vertebral levels. The system was validated using 76 pairs of DXA and LDCT scans of the same subject. Average BMDDXA of L1-L4 was used as the reference standard. Statistically significant (p-value < 0.001) strong correlation is obtained between BMDDXA and BMDCT at all vertebral levels (T1 - L2). A Pearson correlation of 0.857 was achieved between BMDDXA and average BMDCT of T9-T11 by using a 3D ROI taking into account of both trabecular and cortical bone tissue. These encouraging results demonstrate the feasibility of fully automated quantitative BMD assessment and the potential of opportunistic osteoporosis screening with concurrent lung cancer screening using LDCT.

Micropatterning of cells reveals chiral morphogenesis

PubMed Central

2013-01-01

Invariant left-right (LR) patterning or chirality is critical for embryonic development. The loss or reversal of LR asymmetry is often associated with malformations and disease. Although several theories have been proposed, the exact mechanism of the initiation of the LR symmetry has not yet been fully elucidated. Recently, chirality has been detected within single cells as well as multicellular structures using several in vitro approaches. These studies demonstrated the universality of cell chirality, its dependence on cell phenotype, and the role of physical boundaries. In this review, we discuss the theories for developmental LR asymmetry, compare various in vitro cell chirality model systems, and highlight possible roles of cell chirality in stem cell differentiation. We emphasize that the in vitro cell chirality systems have great promise for helping unveil the nature of chiral morphogenesis in development. PMID:23672821

VerSeDa: vertebrate secretome database

PubMed Central

Cortazar, Ana R.; Oguiza, José A.

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. Database URL: VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php PMID:28365718

VerSeDa: vertebrate secretome database.

PubMed

Cortazar, Ana R; Oguiza, José A; Aransay, Ana M; Lavín, José L

2017-01-01

Based on the current tools, de novo secretome (full set of proteins secreted by an organism) prediction is a time consuming bioinformatic task that requires a multifactorial analysis in order to obtain reliable in silico predictions. Hence, to accelerate this process and offer researchers a reliable repository where secretome information can be obtained for vertebrates and model organisms, we have developed VerSeDa (Vertebrate Secretome Database). This freely available database stores information about proteins that are predicted to be secreted through the classical and non-classical mechanisms, for the wide range of vertebrate species deposited at the NCBI, UCSC and ENSEMBL sites. To our knowledge, VerSeDa is the only state-of-the-art database designed to store secretome data from multiple vertebrate genomes, thus, saving an important amount of time spent in the prediction of protein features that can be retrieved from this repository directly. VerSeDa is freely available at http://genomics.cicbiogune.es/VerSeDa/index.php. © The Author(s) 2017. Published by Oxford University Press.

Bone Mineral Properties in Growing Col1a2+/G610C Mice, an animal model of Osteogenesis Imperfecta

PubMed Central

Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Yihe, Huang; Yan, Ma; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

2016-01-01

The Col1a2+/G610C knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2+/G610C and their wild-type controls (Col1a2+/+), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2+/G610C with an LRP+/A214V high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2+/G610C tibias had 13% fewer secondary trabeculae than Col1a2+/+, these were thinner (11%) and more widely spaced (20%) than those of Col1a2+/+ mice. Vertebrae of Col1a2+/G610C mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1a2+/+. The cortical bone of Col1a2+/G610C tibias at 2-months had 3% higher tissue mineral density compared to Col1a2+/+; Col1a2+/G610C vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2+/+. FTIRI analysis, which provides information on bone chemical composition at ~ 7 µm-spatial resolution, showed tibias at 10-days, did not differ between genotypes. Comparing identical bone types in Col1a2+/G610C to Col1a2+/+ at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2+/G610C vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution was noted in 10-day

Molecular signatures that are distinctive characteristics of the vertebrates and chordates and supporting a grouping of vertebrates with the tunicates.

PubMed

Gupta, Radhey S

2016-01-01

Members of the phylum Chordata and the subphylum Vertebrata are presently distinguished solely on the basis of morphological characteristics. The relationship of the vertebrates to the two non-vertebrate chordate subphyla is also a subject of debate. Analyses of protein sequences have identified multiple conserved signature indels (CSIs) that are specific for Chordata or for Vertebrata. Five CSIs in 4 important proteins are specific for the Vertebrata, whereas two other CSIs are uniquely found in all sequenced chordate species including Ciona intestinalis and Oikapleura dioica (Tunicates) as well as Branchiostoma floridae (Cephalochordates). The shared presence of these molecular signatures by all vertebrates/chordate species, but in no other animal taxa, strongly indicates that the genetic changes represented by the identified CSIs diagnose monophyletic groups. Two other discovered CSIs are uniquely shared by different vertebrate species and by either one (Ciona intestinalis) or both tunicate (Ciona and Oikapleura) species, but they are not found in Branchiostoma or other animal species. Specific presence of these CSIs in different vertebrates and either one or both tunicate species provides strong independent evidence that the vertebrate species are more closely related to the urochordates (tunicates) than to the cephalochordates. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression Pattern of the Pro-apoptotic Gene PAR-4 During the Morphogenesis of MCF-10A Human Mammary Epithelial Cells.

PubMed

de Bessa Garcia, Simone A; Pereira, Michelly C; Nagai, Maria A

2010-12-21

The histological organization of the mammary gland involves a spatial interaction of epithelial and myoepithelial cells with the specialized basement membrane (BM), composed of extra-cellular matrix (ECM) proteins, which is disrupted during the tumorigenic process. The interactions between mammary epithelial cells and ECM components play a major role in mammary gland branching morphogenesis. Critical signals for mammary epithelial cell proliferation, differentiation, and survival are provided by the ECM proteins. Three-dimensional (3D) cell culture was developed to establish a system that simulates several features of the breast epithelium in vivo; 3D cell culture of the spontaneously immortalized cell line, MCF10A, is a well-established model system to study breast epithelial cell biology and morphogenesis. Mammary epithelial cells grown in 3D form spheroids, acquire apicobasal polarization, and form lumens that resemble acini structures, processes that involve cell death. Using this system, we evaluated the expression of the pro-apoptotic gene PAWR (PKC apoptosis WT1 regulator; also named PAR-4, prostate apoptosis response-4) by immunofluorescence and quantitative real time PCR (qPCR). A time-dependent increase in PAR-4 mRNA expression was found during the process of MCF10A acinar morphogenesis. Confocal microscopy analysis also showed that PAR-4 protein was highly expressed in the MCF10A cells inside the acini structure. During the morphogenesis of MCF10A cells in 3D cell culture, the cells within the lumen showed caspase-3 activation, indicating apoptotic activity. PAR-4 was only partially co-expressed with activated caspase-3 on these cells. Our results provide evidence, for the first time, that PAR-4 is differentially expressed during the process of MCF10A acinar morphogenesis.

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.

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk

PubMed Central

Jaramillo, Joshua D.; Wilson, Carla; Stinson, Douglas J.; Lynch, David A.; Bowler, Russell P.; Lutz, Sharon; Bon, Jessica M.; Arnold, Ben; McDonald, Merry-Lynn N.; Washko, George R.; Wan, Emily S.; DeMeo, Dawn L.; Foreman, Marilyn G.; Soler, Xavier; Lindsay, Sarah E.; Lane, Nancy E.; Genant, Harry K.; Silverman, Edwin K.; Hokanson, John E.; Make, Barry J.; Crapo, James D.

2015-01-01

Rationale: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered. Objectives: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women. Methods: Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use. Measurements and Main Results: vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk.

PubMed

Jaramillo, Joshua D; Wilson, Carla; Stinson, Douglas S; Stinson, Douglas J; Lynch, David A; Bowler, Russell P; Lutz, Sharon; Bon, Jessica M; Arnold, Ben; McDonald, Merry-Lynn N; Washko, George R; Wan, Emily S; DeMeo, Dawn L; Foreman, Marilyn G; Soler, Xavier; Lindsay, Sarah E; Lane, Nancy E; Genant, Harry K; Silverman, Edwin K; Hokanson, John E; Make, Barry J; Crapo, James D; Regan, Elizabeth A

2015-05-01

Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered. To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women. Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use. vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures. Male smokers, with or

Ovule Morphogenesis in Ranunculaceae and its Systematic Significance

PubMed Central

Wang, Zi-Fen; Ren, Yi

2008-01-01

Background and Aims Ranunculaceae has a prominent phylogenetic position in Ranunculales which appears at the base of eudicots. The aims of the present paper are to reveal the features of ovule morphogenesis in different taxa and gain a better understanding of the systematics of Ranunculaceae. Methods Flowers of 17 species from three subfamilies, nine tribes and 16 genera of Ranunculaceae, at successive developmental stages, were collected in the wild and studied with a scanning electron microscope. Key Results The integuments in the unitegmic ovules in Helleborus, Ranunculus and Oxygraphis, as well as the inner integuments in the bitegmic genera, initiate annularly and eventually become cup-shaped. However, the integuments in the unitegmic ovules in Anemone and Clematis, as well as the outer integuments in the bitegmic genera, arise semi-annularly and eventually become hood-shaped. Different kinds of appendages appear on the ovules during development. In Coptis of subfamily Coptidoideae, a wrap-shaped appendage arises outside the ovule and envelopes the ovule entirely. In the genera of subfamily Thalictroideae and tribe Anemoneae of subfamily Ranunculoideae, appendages appear on the placenta, the funicle or both. In tribe Helleboreae of subfamily Ranunculoideae, an alary appendage is initiated where the integument and the funicle join and becomes hood-shaped. Conclusions Ovule morphogenesis characteristics are significant in classification at the levels of subfamilies and tribes. The initiation patterns of the integuments and the development of appendages show diversity in Ranunculaceae. The present observations suggest that the bitegmic, hood-shaped outer integument and endostomic micropyle are primitive while the unitegmic, cupular-shaped outer integument and bistomic micropyle are derivative. PMID:18065776

Salvage Percutaneous Vertebral Augmentation Using Polymethyl Methacrylate in Patients with Failed Interbody Fusion.

PubMed

Yun, Dong-Ju; Hwang, Byeong-Wook; Oh, Hyeong-Seok; Kim, Jin-Sung; Jeon, Sang-Hyeop; Lee, Sang-Ho

2016-11-01

Percutaneous vertebral augmentation with cement is used as a salvage procedure for failed instrumentation. Few studies have reported the use of this procedure for failed anterior lumbar fusion in elderly patients with osteoporosis and other complicated diseases who have undergone a previous major operation. Between January 2007 and December 2015, the clinical and radiographic results of 8 patients with osteoporosis who showed subsidence and migration of the implant after an initial operation were examined. After the development of implant failure, the patients underwent vertebral augmentation with polymethyl methacrylate. Mean patient age was 73.4 years (range, 67-78 years), and mean bone mineral density was -2.96 (range, -2.1 to -3.8). The mean radiologic follow-up period between augmentation and the last follow-up examination was 16 months (range, 3-38 months). Although the subjective clinical outcome was not satisfying to the patients, no loss of correction, fractures, or screw loosening occurred during the follow-up period. The injection of cement around the instrument might help to stabilize it by providing strength to the axis and preventing further loosening. This salvage procedure could be an alternative in the management of cases with failed interbody fusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Exploring bacteria-induced growth and morphogenesis in the green macroalga order Ulvales (Chlorophyta)

PubMed Central

Wichard, Thomas

2015-01-01

Green macroalgae, such as Ulvales, lose their typical morphology completely when grown under axenic conditions or in the absence of the appropriate microbiome. As a result, slow growing aberrant phenotypes or even callus-like morphotypes are observed in Ulvales. The cross-kingdom interactions between marine algae and microorganisms are hence not only restricted by the exchange of macronutrients, including vitamins and nutrients, but also by infochemicals such as bacterial morphogenetic compounds. The latter are a fundamental trait mediating the mutualism within the chemosphere where the organisms interact with each other via compounds in their surroundings. Approximately 60 years ago, pilot studies demonstrated that certain bacteria promote growth, whereas other bacteria induce morphogenesis; this is particularly true for the order of Ulvales. However, only slow progress was made towards the underlying mechanism due to the complexity of, for example, algal cultivation techniques, and the lack of standardized experiments in the laboratory. A breakthrough in this research was the discovery of the morphogenetic compound thallusin, which was isolated from an epiphytic bacterium and induces normal germination restoring the foliaceous morphotypes of Monostroma. Owing to the low concentration, the purification and structure elucidation of highly biologically active morphogenetic compounds are still challenging. Recently, it was found that only the combination of two specific bacteria from the Rhodobacteraceae and Flavobacteriaceae can completely recover the growth and morphogenesis of axenic Ulva mutabilis cultures forming a symbiotic tripartite community by chemical communication. This review combines literature detailing evidences of bacteria-induced morphogenesis in Ulvales. A set of standardized experimental approaches is further proposed for the preparation of axenic algal tissues, bacteria isolation, co-cultivation experiments, and the analysis of the chemosphere

Building the Vertebrate Spine

NASA Astrophysics Data System (ADS)

Pourquié, Olivier

2008-03-01

The vertebrate body can be subdivided along the antero-posterior (AP) axis into repeated structures called segments. This periodic pattern is established during embryogenesis by the somitogenesis process. Somites are generated in a rhythmic fashion from the paraxial mesoderm and subsequently differentiate to give rise to the vertebrae and skeletal muscles of the body. Somite formation involves an oscillator-the segmentation clock-whose periodic signal is converted into the periodic array of somite boundaries. This clock drives the dynamic expression of cyclic genes in the presomitic mesoderm and requires Notch and Wnt signaling. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the segmentation clock drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the Notch/FGF and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator. In humans, mutations in the genes associated to the function of this oscillator such as Dll3 or Lunatic Fringe result in abnormal segmentation of the vertebral column such as those seen in congenital scoliosis. Whereas the segmentation clock is thought to set the pace of vertebrate segmentation, the translation of this pulsation into the reiterated arrangement of segment boundaries along the AP axis involves dynamic gradients of FGF and Wnt signaling. The FGF signaling gradient is established based on an unusual mechanism involving mRNA decay which provides an efficient means to couple the spatio-temporal activation of segmentation to the posterior elongation of the embryo. Another striking aspect of somite production is the strict bilateral symmetry of the process. Retinoic acid was shown to control aspects of this coordination by buffering destabilizing effects from the embryonic left-right machinery. Defects in this embryonic program controlling vertebral symmetry might lead

Identification of a novel locus on chromosome 2q13, which predisposes to clinical vertebral fractures independently of bone density.

PubMed

Alonso, Nerea; Estrada, Karol; Albagha, Omar M E; Herrera, Lizbeth; Reppe, Sjur; Olstad, Ole K; Gautvik, Kaare M; Ryan, Niamh M; Evans, Kathryn L; Nielson, Carrie M; Hsu, Yi-Hsiang; Kiel, Douglas P; Markozannes, George; Ntzani, Evangelia E; Evangelou, Evangelos; Feenstra, Bjarke; Liu, Xueping; Melbye, Mads; Masi, Laura; Brandi, Maria Luisa; Riches, Philip; Daroszewska, Anna; Olmos, José Manuel; Valero, Carmen; Castillo, Jesús; Riancho, José A; Husted, Lise B; Langdahl, Bente L; Brown, Matthew A; Duncan, Emma L; Kaptoge, Stephen; Khaw, Kay-Tee; Usategui-Martín, Ricardo; Del Pino-Montes, Javier; González-Sarmiento, Rogelio; Lewis, Joshua R; Prince, Richard L; D'Amelio, Patrizia; García-Giralt, Natalia; Nogués, Xavier; Mencej-Bedrac, Simona; Marc, Janja; Wolstein, Orit; Eisman, John A; Oei, Ling; Medina-Gómez, Carolina; Schraut, Katharina E; Navarro, Pau; Wilson, James F; Davies, Gail; Starr, John; Deary, Ian; Tanaka, Toshiko; Ferrucci, Luigi; Gianfrancesco, Fernando; Gennari, Luigi; Lucas, Gavin; Elosua, Roberto; Uitterlinden, André G; Rivadeneira, Fernando; Ralston, Stuart H

2018-03-01

To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication of osteoporosis. Here we conduct a genome-wide association study in 1553 postmenopausal women with clinical vertebral fractures and 4340 controls, with a two-stage replication involving 1028 cases and 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies and bioinformatic studies. A locus tagged by rs10190845 was identified on chromosome 2q13, which was significantly associated with clinical vertebral fracture (P=1.04×10 -9 ) with a large effect size (OR 1.74, 95% CI 1.06 to 2.6). Bioinformatic analysis of this locus identified several potentially functional SNPs that are associated with expression of the positional candidate genes TTL (tubulin tyrosine ligase) and SLC20A1 (solute carrier family 20 member 1). Three other suggestive loci were identified on chromosomes 1p31, 11q12 and 15q11. All these loci were novel and had not previously been associated with bone mineral density or clinical fractures. We have identified a novel genetic variant that is associated with clinical vertebral fractures by mechanisms that are independent of BMD. Further studies are now in progress to validate this association and evaluate the underlying mechanism. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Crk synergizes with epidermal growth factor for epithelial invasion and morphogenesis and is required for the met morphogenic program.

PubMed

Lamorte, Louie; Rodrigues, Sonia; Naujokas, Monica; Park, Morag

2002-10-04

Activation of the Met receptor tyrosine kinase through its ligand, hepatocyte growth factor, stimulates cell spreading, cell dispersal, and the inherent morphogenic program of various epithelial cell lines. Although both hepatocyte growth factor and epidermal growth factor (EGF) can activate downstream signaling pathways in Madin-Darby canine kidney epithelial cells, EGF fails to promote the breakdown of cell-cell junctional complexes and initiate an invasive morphogenic program. We have undertaken a strategy to identify signals that synergize with EGF in this process. We provide evidence that the overexpression of the CrkII adapter protein complements EGF-stimulated pathways to induce cell dispersal in two-dimensional cultures and cell invasion and branching morphogenesis in three-dimensional collagen gels. This finding correlates with the ability of CrkII to promote the breakdown of adherens junctions in stable cell lines and the ability of EGF to stimulate enhanced Rac activity in cells overexpressing CrkII. We have previously shown that the Gab1-docking protein is required for branching morphogenesis downstream of the Met receptor. Consistent with a role for CrkII in promoting EGF-dependent branching morphogenesis, the binding of Gab1 to CrkII is required for the branching morphogenic program downstream of Met. Together, our data support a role for the CrkII adapter protein in epithelial invasion and morphogenesis and underscores the importance of considering the synergistic actions of signaling pathways in cancer progression.

Vertebral fracture after aircraft ejection during Operation Desert Storm.

PubMed

Osborne, R G; Cook, A A

1997-04-01

During Operation Desert Storm, 21 United States and 2 Italian military personnel were held in Iraq as prisoners of war. Of these, 18 had ejected from fixed-wing, ejection seat-equipped, combat aircraft prior to their capture. Of the 18, 6 (33%) had sustained vertebral fractures; 4 of these were compression fractures. This fracture rate is comparable to that of previously studied groups. Fractures were noted to be at several different vertebral sites and after ejecting from a variety of aircraft. Apart from contusions and abrasions, vertebral fractures were the most common injuries discovered in this repatriated population. None of the vertebral fractures produced recognizable neurological disability. The development of vertebral fractures was neither associated with the use of any particular ejection system or aircraft nor did the development of vertebral fractures appear dependent on the age, height or length of service of the affected personnel. Ejected aircrew with low altitude mission profiles seemed more predisposed to vertebral fracture than those at high altitudes, but with a small sample population, this relationship was not statistically significant (p > 0.25). Reliable data were unavailable on aircrew positioning and preparation time for ejection.

Assessing the effects of lumbar posterior stabilization and fusion to vertebral bone density in stabilized and adjacent segments by using Hounsfield unit

PubMed Central

Öksüz, Erol; Deniz, Fatih Ersay; Demir, Osman

2017-01-01

Background Computed tomography (CT) with Hounsfield unit (HU) is being used with increasing frequency for determining bone density. Established correlations between HU and bone density have been shown in the literature. The aim of this retrospective study was to determine the bone density changes of the stabilized and adjacent segment vertebral bodies by comparing HU values before and after lumbar posterior stabilization. Methods Sixteen patients who had similar diagnosis of lumbar spondylosis and stenosis were evaluated in this study. Same surgical procedures were performed to all of the patients with L2-3-4-5 transpedicular screw fixation, fusion and L3-4 total laminectomy. Bone mineral density measurements were obtained with clinical CT. Measurements were obtained from stabilized and adjacent segment vertebral bodies. Densities of vertebral bodies were evaluated with HU before the surgeries and approximately one year after the surgeries. The preoperative HU value of each vertebra was compared with postoperative HU value of the same vertebrae by using statistical analysis. Results The HU values of vertebra in the stabilized and adjacent segments consistently decreased after the operations. There were significant differences between the preoperative HU values and the postoperative HU values of the all evaluated vertebral bodies in the stabilized and adjacent segments. Additionally first sacral vertebra HU values were found to be significantly higher than lumbar vertebra HU values in the preoperative group and postoperative group. Conclusions Decrease in the bone density of the adjacent segment vertebral bodies may be one of the major predisposing factors for adjacent segment disease (ASD). PMID:29354730

[Number of teeth and hormonal profile of postmenopausal women with osteoporosis, osteopenia and normal bone mineral density--a preliminary study].

PubMed

Stagraczyński, Maciej; Kulczyk, Tomasz; Leszczyński, Piotr; Męczekalski, Błażej

2015-10-01

Profound hypoestrogenism causes increased risk of osteoporosis and bone fracture in menopause. This period of women life is also characterized by decrease number of teeth and deterioration of oral cavity health. The aim of the study was to assess the number of teeth, hormonal profile (Follicle-stimualting hormone (FSH), estradiol (E2), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) and the bone mineral density (BMD) of the lumbar part of the spine in postmenopausal women with osteoporosis, osteopenia and normal BMD. The next step of the study was to determine whether there was a correlation between vertebral mineral bone density, the hormonal profile and the number of teeth. A total number of 47 women was involved in the study. Based on the results of densitometry tests (DEXA) of vertebral column the subjects were divided into 3 groups: 10 with osteoporosis, 20 with osteopenia and 17 with normal BMD. All the subjects had undergone a hormonal assessment which included blood serum estimation for FSH, E2, DHEA-S and T levels. Also the total number of teeth present was recorded. Serum estradiol and testosterone levels in postmenopausal women were found to be positively correlated with the number of teeth present. A negative correlation was found between age and the number of maxillary teeth in postmenopausal women with osteopenia. There was no influence of serum FSH, estradiol, testosterone and DHEA-S levels on vertebral BMD loss in postmenopausal women. There was no correlation between teeth number and BMD of vertebral column. Serum levels of estradiol and testosterone in postmenopausal women positively correlate with teeth numbers. Age is the main risk factor for teeth loss in postmenopausal women. © 2015 MEDPRESS.

The CW domain, a structural module shared amongst vertebrates, vertebrate-infecting parasites and higher plants.

PubMed

Perry, Jason; Zhao, Yunde

2003-11-01

A previously undetected domain, named CW for its conserved cysteine and tryptophan residues, appears to be a four-cysteine zinc-finger motif found exclusively in vertebrates, vertebrate-infecting parasites and higher plants. Of the twelve distinct nuclear protein families that comprise the CW domain-containing superfamily, only the microrchida (MORC) family has begun to be characterized. However, several families contain other domains suggesting a relationship between the CW domain and either chromatin methylation status or early embryonic development.

Kyphoplasty for vertebral augmentation in the elderly with osteoporotic vertebral compression fractures: scenarios and review of recent studies.

PubMed

Bednar, Timothy; Heyde, Christoph E; Bednar, Grace; Nguyen, David; Volpi, Elena; Przkora, Rene

2013-11-01

Vertebral compression fractures caused by osteoporosis are among the most common fractures in the elderly. The treatment focuses on pain control, maintenance of independence, and management of the osteoporosis. Elderly patients often encounter adverse effects to pain medications, do not tolerate bed rest, and are not ideal candidates for invasive spinal reconstructive surgery. Percutaneous vertebral augmentation (vertebroplasty or kyphoplasty) has become popular as a less-invasive alternative. However, studies have questioned the effectiveness of these procedures. The authors conducted a MEDLINE search using relevant search terms including osteoporosis, osteoporotic vertebral compression fracture, elderly, kyphoplasty and vertebroplasty. Two elderly patients presented with a fracture of their third and first lumbar vertebral body, respectively. One patient progressed well with conservative treatment, whereas the other patient was hospitalized secondary to pain after conservative measures failed to offer improvement. The hospitalized patient subsequently opted for a kyphoplasty and was able to resume his normal daily activities after the procedure. Selecting patients on an individual case-by-case basis can optimize the effectiveness and outcomes of a vertebral augmentation. This process includes the documentation of an osteoporotic vertebral compression fracture with the aide of imaging studies, including the acuity of the fracture as well as the correlation with the physical examination findings. Patients who are functional and improving under a conservative regimen are not candidates for kyphoplasty. However, if the conservative management is not successful after 4 to 6 weeks and the patient is at risk to become bedridden, an augmentation should be considered. A kyphoplasty procedure may be preferred over vertebroplasty, given the lower risk profile and better outcomes regarding spinal alignment. Published by Elsevier HS Journals, Inc.

Non-contiguous multifocal vertebral osteomyelitis caused by Serratia marcescens.

PubMed

Lau, Jen Xin; Li, Jordan Yuanzhi; Yong, Tuck Yean

2015-03-01

Serratia marcescens is a common nosocomial infection but a rare cause of osteomyelitis and more so of vertebral osteomyelitis. Vertebral osteomyelitis caused by this organism has been reported in few studies. We report a case of S. marcescens vertebral discitis and osteomyelitis affecting multiple non-contiguous vertebras. Although Staphylococcus aureus is the most common cause of vertebral osteomyelitis, rare causes, such as S. marcescens, need to be considered, especially when risk factors such as intravenous heroin use, post-spinal surgery and immunosuppression are present. Therefore, blood culture and where necessary biopsy of the infected region should be undertaken to establish the causative organism and determine appropriate antibiotic susceptibility. Prompt diagnosis of S. marcescens vertebral osteomyelitis followed by the appropriate treatment can achieve successful outcomes.

Embryonic lung morphogenesis in organ culture: experimental evidence for a proteoglycan function in the extracellular matrix

NASA Technical Reports Server (NTRS)

Spooner, B. S.; Bassett, K. E.; Spooner, B. S. Jr

1993-01-01

The lung rudiment, isolated from mid-gestation (11 day) mouse embryos, can undergo morphogenesis in organ culture. Observation of living rudiments, in culture, reveals both growth and ongoing bronchiolar branching activity. To detect proteoglycan (PG) biosynthesis, and deposition in the extracellular matrix, rudiments were metabolically labeled with radioactive sulfate, then fixed, embedded, sectioned and processed for autoradiography. The sulfated glycosaminoglycan (GAG) types, composing the carbohydrate component of the proteoglycans, were evaluated by selective GAG degradative approaches that showed chondroitin sulfate PG principally associated with the interstitial matrix, and heparan sulfate PG principally associated with the basement membrane. Experiments using the proteoglycan biosynthesis disrupter, beta-xyloside, suggest that when chondroitin sulfate PG deposition into the ECM is perturbed, branching morphogenesis is compromised.

Vertebral Adaptations to Large Body Size in Theropod Dinosaurs.

PubMed

Wilson, John P; Woodruff, D Cary; Gardner, Jacob D; Flora, Holley M; Horner, John R; Organ, Chris L

2016-01-01

Rugose projections on the anterior and posterior aspects of vertebral neural spines appear throughout Amniota and result from the mineralization of the supraspinous and interspinous ligaments via metaplasia, the process of permanent tissue-type transformation. In mammals, this metaplasia is generally pathological or stress induced, but is a normal part of development in some clades of birds. Such structures, though phylogenetically sporadic, appear throughout the fossil record of non-avian theropod dinosaurs, yet their physiological and adaptive significance has remained unexamined. Here we show novel histologic and phylogenetic evidence that neural spine projections were a physiological response to biomechanical stress in large-bodied theropod species. Metaplastic projections also appear to vary between immature and mature individuals of the same species, with immature animals either lacking them or exhibiting smaller projections, supporting the hypothesis that these structures develop through ontogeny as a result of increasing bending stress subjected to the spinal column. Metaplastic mineralization of spinal ligaments would likely affect the flexibility of the spinal column, increasing passive support for body weight. A stiff spinal column would also provide biomechanical support for the primary hip flexors and, therefore, may have played a role in locomotor efficiency and mobility in large-bodied species. This new association of interspinal ligament metaplasia in Theropoda with large body size contributes additional insight to our understanding of the diverse biomechanical coping mechanisms developed throughout Dinosauria, and stresses the significance of phylogenetic methods when testing for biological trends, evolutionary or not.

Handed behavior in hagfish--an ancient vertebrate lineage--and a survey of lateralized behaviors in other invertebrate chordates and elongate vertebrates.

PubMed

Miyashita, Tetsuto; Palmer, A Richard

2014-04-01

Hagfish represent an ancient lineage of boneless and jawless vertebrates. Among several curious behaviors they exhibit, solitary individuals in one dominant genus of hagfish (Eptatretus spp.) regularly rest in a tightly coiled posture. We present the first systematic treatment of this distinctive behavior. Individual northeastern Pacific hagfish (E. stoutii) exhibited significant handedness (preferred orientation of coiling). However, right-coiling and left-coiling individuals were equally common in the population. Individual hagfish likely develop a preference for one direction by repeating the preceding coiling direction. We also revisit classical accounts of chordate natural history and compare the coiling behavior of Eptatretus with other handed or lateralized behaviors in non-vertebrate chordates, lampreys, and derived vertebrates with elongate bodies. Handed behaviors occur in many of these groups, but they likely evolved independently. In contrast to vertebrates, morphological asymmetries may bias lateralized larval behaviors toward one side in cephalochordates and tunicates. As a consequence, no known handed behavior can be inferred to have existed in the common ancestor of vertebrates.

Health state utility values and patient-reported outcomes before and after vertebral and non-vertebral fractures in an osteoporosis clinical trial.

PubMed

Imai, T; Tanaka, S; Kawakami, K; Miyazaki, T; Hagino, H; Shiraki, M

2017-06-01

We assessed the health state utility value (HSUV) reductions associated with vertebral fractures using data collected in the Japanese Osteoporosis Intervention Trial-03 (JOINT-03). Our analysis revealed that assessment of HSUVs after morphometric vertebral fracture is important to capture the burden of vertebral fractures. Evaluation of the HSUV after fracture is important to calculate the quality-adjusted life years (QALYs) of osteoporosis patients, which is essential information in the context of health economic evaluation. JOINT-03 study patients were aged ≥65 years and treated with risedronate and vitamin K 2 or risedronate alone. Radiographic information and patient-reported outcomes measured by EQ-5D and a visual analogue scale (VAS) were assessed at registration and followed up after 6, 12, and 24 months. According to differences among the dates of these assessments and the radiographic information, we classified the follow-up HSUVs calculated based on EQ-5D results into before or after fracture categories regardless of clinical symptoms. Among 2922 follow-up HSUVs, 201 HSUVs were categorized as HSUVs that were observed after incident vertebral fractures on X-ray films. The median time from the detection of an incident vertebral fracture until the EQ-5D assessment was 53 days (25th percentile, 0 day; 75th percentile, 357 days). The impact of incident vertebral fractures on HSUVs was quantified as -0.03. Among the five health profile domains on the EQ-5D, an incident vertebral fracture had significant effects on anxiety/depression, self-care, and usual activities. The results suggest that incident morphometric vertebral fracture was associated with impairment of the HSUV for patients with osteoporosis not only immediately but also several months after the fracture.

Caudal lumbar vertebral fractures in California Quarter Horse and Thoroughbred racehorses.

PubMed

Collar, E M; Zavodovskaya, R; Spriet, M; Hitchens, P L; Wisner, T; Uzal, F A; Stover, S M

2015-09-01

To gain insight into the pathophysiology of equine lumbar vertebral fractures in racehorses. To characterise equine lumbar vertebral fractures in California racehorses. Retrospective case series and prospective case-control study. Racehorse post mortem reports and jockey injury reports were retrospectively reviewed. Vertebral specimens from 6 racehorses affected with lumbar vertebral fractures and 4 control racehorses subjected to euthanasia for nonspinal fracture were assessed using visual, radiographic, computed tomography and histological examinations. Lumbar vertebral fractures occurred in 38 Quarter Horse and 29 Thoroughbred racehorses over a 22 year period, primarily involving the 5th and/or 6th lumbar vertebrae (L5-L6; 87% of Quarter Horses and 48% of Thoroughbreds). Lumbar vertebral fractures were the third most common musculoskeletal cause of death in Quarter Horses and frequently involved a jockey injury. Lumbar vertebral specimens contained anatomical variations in the number of vertebrae, dorsal spinous processes and intertransverse articulations. Lumbar vertebral fractures examined in 6 racehorse specimens (5 Quarter Horses and one Thoroughbred) coursed obliquely in a cranioventral to caudodorsal direction across the adjacent L5-L6 vertebral endplates and intervertebral disc, although one case involved only one endplate. All cases had evidence of abnormalities on the ventral aspect of the vertebral bodies consistent with pre-existing, maladaptive pathology. Lumbar vertebral fractures occur in racehorses with pre-existing pathology at the L5-L6 vertebral junction that is likely predisposes horses to catastrophic fracture. Knowledge of these findings should encourage assessment of the lumbar vertebrae, therefore increasing detection of mild vertebral injuries and preventing catastrophic racehorse and associated jockey injuries. © 2014 EVJ Ltd.

Late development of hagfish vertebral elements.

PubMed

Ota, Kinya G; Fujimoto, Satoko; Oisi, Yasuhiro; Kuratani, Shigeru

2013-05-01

It has been demonstrated recently that hagfishes, one of two groups of extant jawless vertebrates, have cartilaginous vertebral elements. Embryological and gene expression analyses have also shown that this group of animals develops a sclerotome, the potential primordium of the axial skeleton. However, it has not been shown unequivocally that the hagfish sclerotome truly differentiates into cartilage, because access to late-stage embryos and information about the cartilaginous extracellular matrix (ECM) are lacking for these animals. Here we investigated the expression patterns of the biglycan/decorin (BGN/DCN) gene in the inshore hagfish, Eptatretus burgeri. The homologue of this gene encodes the major noncollagenous component of the cartilaginous ECM among gnathostomes. We clearly identified the expression of this gene in adult vertebral tissues and in embryonic mesenchymal cells on the ventral aspect of the notochord. Taking into account that the sclerotome in the gnathostomes expresses BGN/DCN gene during the chondrogenesis, it is highly expected the hagfish BGN/DCN-positive mesenchymal cells are derived from the sclerotomes. We propose that hagfishes and gnathostomes share conserved developmental mechanisms not only in their somite differentiation, but also in chondrogenesis of their vertebral elements. Copyright © 2013 Wiley Periodicals, Inc.

Reintroduction of locally extinct vertebrates impacts arid soil fungal communities.

PubMed

Clarke, Laurence J; Weyrich, Laura S; Cooper, Alan

2015-06-01

Introduced species have contributed to extinction of native vertebrates in many parts of the world. Changes to vertebrate assemblages are also likely to alter microbial communities through coextinction of some taxa and the introduction of others. Many attempts to restore degraded habitats involve removal of exotic vertebrates (livestock and feral animals) and reintroduction of locally extinct species, but the impact of such reintroductions on microbial communities is largely unknown. We used high-throughput DNA sequencing of the fungal internal transcribed spacer I (ITS1) region to examine whether replacing exotic vertebrates with reintroduced native vertebrates led to changes in soil fungal communities at a reserve in arid central Australia. Soil fungal diversity was significantly different between dune and swale (interdune) habitats. Fungal communities also differed significantly between sites with exotic or reintroduced native vertebrates after controlling for the effect of habitat. Several fungal operational taxonomic units (OTUs) found exclusively inside the reserve were present in scats from reintroduced native vertebrates, providing a direct link between the vertebrate assemblage and soil microbial communities. Our results show that changes to vertebrate assemblages through local extinctions and the invasion of exotic species can alter soil fungal communities. If local extinction of one or several species results in the coextinction of microbial taxa, the full complement of ecological interactions may never be restored. © 2015 John Wiley & Sons Ltd.

Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates.

PubMed

Holzer, Guillaume; Morishita, Yoshiaki; Fini, Jean-Baptiste; Lorin, Thibault; Gillet, Benjamin; Hughes, Sandrine; Tohmé, Marie; Deléage, Gilbert; Demeneix, Barbara; Arvan, Peter; Laudet, Vincent

2016-08-05

Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central nervous system function, seasonal changes in physiology, and behavior) but also in some non-vertebrates where they control critical post-embryonic developmental transitions such as metamorphosis. Despite their obvious biological importance, the thyroid hormone precursor protein, thyroglobulin (Tg), has been experimentally investigated only in mammals. This may bias our view of how thyroid hormones are produced in other organisms. In this study we searched genomic databases and found Tg orthologs in all vertebrates including the sea lamprey (Petromyzon marinus). We cloned a full-size Tg coding sequence from western clawed frog (Xenopus tropicalis) and zebrafish (Danio rerio). Comparisons between the representative mammal, amphibian, teleost fish, and basal vertebrate indicate that all of the different domains of Tg, as well as Tg regional structure, are conserved throughout the vertebrates. Indeed, in Xenopus, zebrafish, and lamprey Tgs, key residues, including the hormonogenic tyrosines and the disulfide bond-forming cysteines critical for Tg function, are well conserved despite overall divergence of amino acid sequences. We uncovered upstream sequences that include start codons of zebrafish and Xenopus Tgs and experimentally proved that these are full-length secreted proteins, which are specifically recognized by antibodies against rat Tg. By contrast, we have not been able to find any orthologs of Tg among non-vertebrate species. Thus, Tg appears to be a novel protein elaborated as a single event at the base of vertebrates and virtually unchanged thereafter. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Analysis of maternal-zygotic ugdh mutants reveals divergent roles for HSPGs in vertebrate embryogenesis and provides new insight into the initiation of left-right asymmetry.

PubMed

Superina, Simone; Borovina, Antonia; Ciruna, Brian

2014-03-15

Growth factors and morphogens regulate embryonic patterning, cell fate specification, cell migration, and morphogenesis. The activity and behavior of these signaling molecules are regulated in the extracellular space through interactions with proteoglycans (Bernfield et al., 1999; Perrimon and Bernfield 2000; Lander and Selleck 2000; Selleck 2000). Proteoglycans are high molecular-weight proteins consisting of a core protein with covalently linked glycosaminoglycan (GAG) side chains, which are thought to mediate ligand interaction. Drosophila mutant embryos deficient for UDP-glucose dehydrogenase activity (Ugdh, required for GAG synthesis) exhibit abnormal Fgf, Wnt and TGFß signaling and die during gastrulation, indicating a broad and critical role for proteoglycans during early embryonic development (Lin et al., 1999; Lin and Perrimon 2000) (Hacker et al., 1997). Mouse Ugdh mutants also die at gastrulation, however, only Fgf signaling appears disrupted (Garcia-Garcia and Anderson, 2003). These findings suggested a possible divergence in the requirement for proteoglycans during Drosophila and mouse embryogenesis, and that mammals may have evolved alternative means of regulating Wnt and TGFß activity. To further examine the function of proteoglycans in vertebrate development, we have characterized zebrafish mutants devoid of both maternal and zygotic Ugdh/Jekyll activity (MZjekyll). We demonstrate that MZjekyll mutant embryos display abnormal Fgf, Shh, and Wnt signaling activities, with concomitant defects in central nervous system patterning, cardiac ventricular fate specification and axial morphogenesis. Furthermore, we uncover a novel role for proteoglycans in left-right pattern formation. Our findings resolve longstanding questions into the evolutionary conservation of Ugdh function and provide new mechanistic insights into the initiation of left-right asymmetry. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Vertebrate richness and biogeography in the Big Thicket of Texas

Treesearch

Michael H MacRoberts; Barbara R. MacRoberts; D. Craig Rudolph

2010-01-01

The Big Thicket of Texas has been described as rich in species and a “crossroads:” a place where organisms from many different regions meet. We examine the species richness and regional affiliations of Big Thicket vertebrates. We found that the Big Thicket is neither exceptionally rich in vertebrates nor is it a crossroads for vertebrates. Its vertebrate fauna is...

Imperfect isolation: factors and filters shaping Madagascar's extant vertebrate fauna.

PubMed

Samonds, Karen E; Godfrey, Laurie R; Ali, Jason R; Goodman, Steven M; Vences, Miguel; Sutherland, Michael R; Irwin, Mitchell T; Krause, David W

2013-01-01

Analyses of phylogenetic topology and estimates of divergence timing have facilitated a reconstruction of Madagascar's colonization events by vertebrate animals, but that information alone does not reveal the major factors shaping the island's biogeographic history. Here, we examine profiles of Malagasy vertebrate clades through time within the context of the island's paleogeographical evolution to determine how particular events influenced the arrival of the island's extant groups. First we compare vertebrate profiles on Madagascar before and after selected events; then we compare tetrapod profiles on Madagascar to contemporary tetrapod compositions globally. We show that changes from the Mesozoic to the Cenozoic in the proportions of Madagascar's tetrapod clades (particularly its increase in the representation of birds and mammals) are tied to changes in their relative proportions elsewhere on the globe. Differences in the representation of vertebrate classes from the Mesozoic to the Cenozoic reflect the effects of extinction (i.e., the non-random susceptibility of the different vertebrate clades to purported catastrophic global events 65 million years ago), and new evolutionary opportunities for a subset of vertebrates with the relatively high potential for transoceanic dispersal potential. In comparison, changes in vertebrate class representation during the Cenozoic are minor. Despite the fact that the island's isolation has resulted in high vertebrate endemism and a unique and taxonomically imbalanced extant vertebrate assemblage (both hailed as testimony to its long isolation), that isolation was never complete. Indeed, Madagascar's extant tetrapod fauna owes more to colonization during the Cenozoic than to earlier arrivals. Madagascar's unusual vertebrate assemblage needs to be understood with reference to the basal character of clades originating prior to the K-T extinction, as well as to the differential transoceanic dispersal advantage of other, more

A unified anatomy ontology of the vertebrate skeletal system.

PubMed

Dahdul, Wasila M; Balhoff, James P; Blackburn, David C; Diehl, Alexander D; Haendel, Melissa A; Hall, Brian K; Lapp, Hilmar; Lundberg, John G; Mungall, Christopher J; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E; Vickaryous, Matthew K; Westerfield, Monte; Mabee, Paula M

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A Unified Anatomy Ontology of the Vertebrate Skeletal System

PubMed Central

Dahdul, Wasila M.; Balhoff, James P.; Blackburn, David C.; Diehl, Alexander D.; Haendel, Melissa A.; Hall, Brian K.; Lapp, Hilmar; Lundberg, John G.; Mungall, Christopher J.; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E.; Vickaryous, Matthew K.; Westerfield, Monte; Mabee, Paula M.

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity. PMID:23251424

Vertex Models of Epithelial Morphogenesis

PubMed Central

Fletcher, Alexander G.; Osterfield, Miriam; Baker, Ruth E.; Shvartsman, Stanislav Y.

2014-01-01

The dynamic behavior of epithelial cell sheets plays a central role during numerous developmental processes. Genetic and imaging studies of epithelial morphogenesis in a wide range of organisms have led to increasingly detailed mechanisms of cell sheet dynamics. Computational models offer a useful means by which to investigate and test these mechanisms, and have played a key role in the study of cell-cell interactions. A variety of modeling approaches can be used to simulate the balance of forces within an epithelial sheet. Vertex models are a class of such models that consider cells as individual objects, approximated by two-dimensional polygons representing cellular interfaces, in which each vertex moves in response to forces due to growth, interfacial tension, and pressure within each cell. Vertex models are used to study cellular processes within epithelia, including cell motility, adhesion, mitosis, and delamination. This review summarizes how vertex models have been used to provide insight into developmental processes and highlights current challenges in this area, including progressing these models from two to three dimensions and developing new tools for model validation. PMID:24896108

Ketoconazole inhibits Malassezia furfur morphogenesis in vitro under filamentation optimized conditions.

PubMed

Youngchim, Sirida; Nosanchuk, Joshua D; Chongkae, Siriporn; Vanittanokom, Nongnuch

2017-01-01

Malassezia furfur, a constituent of the normal human skin flora, is an etiological agent of pityriasis versicolor, which represents one of the most common human skin diseases. Under certain conditions, both exogenous and endogenous, the fungus can transition from a yeast form to a pathogenic mycelial form. To develop a standardized medium for reproducible production of the mycelial form of M. furfur to develop and optimize susceptibility testing for this pathogen, we examined and characterized variables, including kojic acid and glycine concentration, agar percentage, and pH, to generate a chemically defined minimal medium on which specific inoculums of M. furfur generated the most robust filamentation. Next, we examined the capacity of ketoconazole to inhibit the formation of M. furfur mycelial form. Both low and high, 0.01, 0.05 and 0.1 µg/ml concentrations of ketoconazole significantly inhibited filamentation at 11.9, 54.5 and 86.7%, respectively. Although ketoconazole can have a direct antifungal effect on both M. furfur yeast and mycelial cells, ketoconazole also has a dramatic impact on suppressing morphogenesis. Since mycelia typified the pathogenic form of Malassezia infection, the capacity of ketoconazole to block morphogenesis may represent an additional important effect of the antifungal.

Biologic disease-modifying anti-rheumatic drugs and the risk of non-vertebral osteoporotic fractures in patients with rheumatoid arthritis aged 50 years and over.

PubMed

Roussy, J-P; Bessette, L; Bernatsky, S; Rahme, E; Lachaine, J

2013-09-01

Prevention of bone mineral density loss in rheumatoid arthritis (RA) has been associated with use of biologic disease-modifying anti-rheumatic drugs (DMARDs). However, in this study, we could not demonstrate a reduction in the risk of non-vertebral fractures. Additional research is required to clarify the impact of biologic DMARDs on fracture risk in RA. Small studies have suggested biologic DMARDs preserve bone mineral density at 6-12 months. Our objective was to determine the association between biologic DMARD use and the risk of non-vertebral osteoporotic fractures in RA subjects aged ≥50 years. A nested case-control study was conducted using Quebec physician billing and hospital discharge data. RA subjects were identified from International Classification of Disease-9/10 codes in billing and hospitalisation data and followed from cohort entry until the earliest of non-vertebral osteoporotic fracture, death, or end of study period. Controls were matched to cases (4:1 ratio) on age, sex, and date of cohort entry. Biologic DMARD exposure was defined as being on treatment for ≥180 days pre-fracture (index). Conditional logistic regression was used, adjusting for indicators of RA severity, comorbidity, drugs influencing fracture risk, and measures of health care utilisation. Over the study period, 1,515 cases were identified (6,023 controls). The most frequent fracture site was hip/femur (42.3%). In total, 172 subjects (49 cases and 123 controls) were exposed to biologic DMARDs. The median duration of exposure was 735 (interquartile range (IQR), 564) and 645 (IQR, 903) days in cases and controls, respectively. We were unable to demonstrate an association between biologic DMARDs and fracture risk (odds ratio, 1.03; 95% confidence interval, 0.42-2.53). RA duration significantly increased the fracture risk. Despite the positive impact of biologic DMARDs on bone remodelling observed in small studies, we were unable to demonstrate a reduction in the risk of non-vertebral

Turing mechanism underlying a branching model for lung morphogenesis.

PubMed

Xu, Hui; Sun, Mingzhu; Zhao, Xin

2017-01-01

The mammalian lung develops through branching morphogenesis. Two primary forms of branching, which occur in order, in the lung have been identified: tip bifurcation and side branching. However, the mechanisms of lung branching morphogenesis remain to be explored. In our previous study, a biological mechanism was presented for lung branching pattern formation through a branching model. Here, we provide a mathematical mechanism underlying the branching patterns. By decoupling the branching model, we demonstrated the existence of Turing instability. We performed Turing instability analysis to reveal the mathematical mechanism of the branching patterns. Our simulation results show that the Turing patterns underlying the branching patterns are spot patterns that exhibit high local morphogen concentration. The high local morphogen concentration induces the growth of branching. Furthermore, we found that the sparse spot patterns underlie the tip bifurcation patterns, while the dense spot patterns underlies the side branching patterns. The dispersion relation analysis shows that the Turing wavelength affects the branching structure. As the wavelength decreases, the spot patterns change from sparse to dense, the rate of tip bifurcation decreases and side branching eventually occurs instead. In the process of transformation, there may exists hybrid branching that mixes tip bifurcation and side branching. Since experimental studies have reported that branching mode switching from side branching to tip bifurcation in the lung is under genetic control, our simulation results suggest that genes control the switch of the branching mode by regulating the Turing wavelength. Our results provide a novel insight into and understanding of the formation of branching patterns in the lung and other biological systems.

Prevalent and Incident Vertebral Deformities in Midlife Women: Results from the Study of Women's Health Across the Nation (SWAN).

PubMed

Greendale, Gail A; Wilhalme, Holly; Huang, Mei-Hua; Cauley, Jane A; Karlamangla, Arun S

Vertebral fractures are the most common type of osteoporotic fracture among women, but estimates of their prevalence and incidence during middle-age are limited. The development of vertebral morphometry (VM) using dual energy X-ray absorptiometry (DXA) makes it more feasible to measure VM in large, longitudinal, observational studies. We conducted this study to: 1) contribute to the scant knowledge of the prevalence, incidence and risk factors for vertebral deformities in middle-aged women; and 2) to evaluate the performance of DXA-based VM measurement in a large, community based sample. The sample is derived from the Study of Women's Health Across the Nation (SWAN), a multi-site, community-based, longitudinal cohort study of the MT. Using Hologic QDR 4500A instruments, we acquired initial VM measurements in 1446 women during calendar years 2004-2007; in 2012-2013, a follow-up VM was obtained in 1108. Annually, lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) were measured and participant characteristics were assessed with standardized instruments. Multivariable logistic regression models examined the relations between prevalent deformity and relevant characteristics. Analyses of characteristics associated with prevalent deformity were restricted to 824 women who had not taken bone active medications since SWAN baseline. We calculated incident deformity per person year (PY) of observation, standardized to 1000 person-years. The cranial portion of the VM image yielded the lowest proportions of readable vertebrae: from T4 through T6, between 43% and 63% of vertebral bodies were evaluable. Greater BMI was associated with fewer readable levels (B = -0.088, p<0.0001). In the baseline sample of 1446 women, the prevalence of vertebral deformity was 3.2% (95% CI: 2.3, 4.1). The relative odds of deformity increased by 61% per SD decrement in baseline LS BMD (p = 0.02) and were 67% greater per SD decrement in baseline FN BMD (p = 0.04). Odds of prevalent

Cervical vertebral erosion caused by bilateral vertebral artery tortuosity, predisposing to spinal, sprain: A medieval case study.

PubMed

Darton, Yves

2014-03-01

Bone resorption within the cervical spine due to vertebral arterial tortuosities is rarely observed in medical practice because the condition often lacks clinical symptoms. Traumatic complications involving the vertebral arteries are relatively common and occasionally very serious, but very few affect bone, appearing only when survival has been sufficiently long for a pseudoaneurysm to form. CT scans and MRI screening, practised increasingly today following traffic and sports accidents, incidentally show that arterial tortuosities that had stimulated bone resorption are relatively frequent. Only rarely do such tortuosities cause nerve compression or trigger orthopaedic problems, while large pseudoaneurysms and congenital absence of a vertebral pedicle may require surgery to stabilize the spine. There are few publications by palaeopathologists reporting such conditions of the cervical vertebrae. This contribution reports a case of a tiered bilateral tortuosity of the vertebral artery dating from the Early Middle Ages; it provides a basis by which to recognize this type of lesion in osteoarchaeology, and it attests to the fact that multiple tortuosities may lead to spinal instability in the form of spine sprain. Copyright © 2013 Elsevier Inc. All rights reserved.

Mechanical Loading during Growth Is Associated with Plane-specific Differences in Vertebral Geometry: A Cross-sectional Analysis Comparing Artistic Gymnasts vs. Non-gymnasts

PubMed Central

Dowthwaite, Jodi N.; Rosenbaum, Paula F.; Scerpella, Tamara A.

2011-01-01

Lumbar spine geometry, density and indices of bone strength were assessed relative to menarche status, using artistic gymnastics exposure during growth as a model of mechanical loading. Paired posteroanterior (PA) and supine lateral (LAT) DXA scans of L3 for 114 females (60 ex/gymnasts and 54 non-gymnasts) yielded output for comparison of paired (PALAT) versus standard PA and LAT outcomes. BMC, areal BMD, vertebral body dimensions, bone mineral apparent density (BMAD), axial compressive strength (IBS) and a fracture risk index were evaluated, modeling vertebral body geometry as an ellipsoid cylinder. Two-factor ANCOVA tested statistical effects of gymnastic exposure, menarche status and their interaction, adjusting for age and height as appropriate. Compared to non-gymnasts, ex/gymnasts exhibited greater PABMD, PABMC, PAWIDTH, PA CROSS-SECTIONAL AREA (CSA), PAVOLUME, LATBMD, LATBMAD, PALATCSA and PALATIBS (p<0.05). Non-gymnasts exhibited greater LATDEPTH/PAWIDTH, LATBMC/PABMC, LATVHEIGHT, LATAREA and Fracture Risk Index. Using ellipsoid vertebral geometric models, no significant differences were detected for PA or PALAT BMAD. In contrast, cuboid model results (Carter 1992) suggested erroneous ex/gymnast PABMAD advantages, resulting from invalid assumptions of proportional variation in linear skeletal dimensions. Gymnastic exposure was associated with shorter, wider vertebral bodies, yielding greater axial compressive strength and lower fracture risk, despite no BMAD advantage. Our results suggest the importance of plane-specific vertebral geometric adaptation to mechanical loading during growth. Paired scan output provides a more accurate assessment of this adaptation than PA or LAT plane scans alone. PMID:21839871

The vertebral column of Australopithecus sediba.

PubMed

Williams, Scott A; Ostrofsky, Kelly R; Frater, Nakita; Churchill, Steven E; Schmid, Peter; Berger, Lee R

2013-04-12

Two partial vertebral columns of Australopithecus sediba grant insight into aspects of early hominin spinal mobility, lumbar curvature, vertebral formula, and transitional vertebra position. Au. sediba likely possessed five non-rib-bearing lumbar vertebrae and five sacral elements, the same configuration that occurs modally in modern humans. This finding contrasts with other interpretations of early hominin regional vertebral numbers. Importantly, the transitional vertebra is distinct from and above the last rib-bearing vertebra in Au. sediba, resulting in a functionally longer lower back. This configuration, along with a strongly wedged last lumbar vertebra and other indicators of lordotic posture, would have contributed to a highly flexible spine that is derived compared with earlier members of the genus Australopithecus and similar to that of the Nariokotome Homo erectus skeleton.

The morphogenesis of feathers.

PubMed

Yu, Mingke; Wu, Ping; Widelitz, Randall B; Chuong, Cheng-Ming

2002-11-21

Feathers are highly ordered, hierarchical branched structures that confer birds with the ability of flight. Discoveries of fossilized dinosaurs in China bearing 'feather-like' structures have prompted interest in the origin and evolution of feathers. However, there is uncertainty about whether the irregularly branched integumentary fibres on dinosaurs such as Sinornithosaurus are truly feathers, and whether an integumentary appendage with a major central shaft and notched edges is a non-avian feather or a proto-feather. Here, we use a developmental approach to analyse molecular mechanisms in feather-branching morphogenesis. We have used the replication-competent avian sarcoma retrovirus to deliver exogenous genes to regenerating flight feather follicles of chickens. We show that the antagonistic balance between noggin and bone morphogenetic protein 4 (BMP4) has a critical role in feather branching, with BMP4 promoting rachis formation and barb fusion, and noggin enhancing rachis and barb branching. Furthermore, we show that sonic hedgehog (Shh) is essential for inducing apoptosis of the marginal plate epithelia, which results in spaces between barbs. Our analyses identify the molecular pathways underlying the topological transformation of feathers from cylindrical epithelia to the hierarchical branched structures, and provide insights on the possible developmental mechanisms in the evolution of feather forms.

Morphogenesis of Dengue Virus: Molecular Biology and Molecular Organization of Proteins.

DTIC Science & Technology

1981-02-01

envelope and near the virion surface. The divalent cations probably act to stabilize viral envelope proteins, as recently found for feline leukemia ... Virus Sindbis virus (SV) and Semliki Forest Virus (SFV) are arthopod-borne alDhaviruses of the toqavirus family. Both viruses contain a nucleocaosid...AU-AIZ9 b"J MORPHOGENESIS OF DENGUE VIRUS : MOLECULAR BIO0OGY AND MOLECULAR ORGANIZATION OFPROENS(U CALIORNIAUNIV DAVIS DEPT 0F BACTERIOLO0Y J S

Automated 3D closed surface segmentation: application to vertebral body segmentation in CT images.

PubMed

Liu, Shuang; Xie, Yiting; Reeves, Anthony P

2016-05-01

A fully automated segmentation algorithm, progressive surface resolution (PSR), is presented in this paper to determine the closed surface of approximately convex blob-like structures that are common in biomedical imaging. The PSR algorithm was applied to the cortical surface segmentation of 460 vertebral bodies on 46 low-dose chest CT images, which can be potentially used for automated bone mineral density measurement and compression fracture detection. The target surface is realized by a closed triangular mesh, which thereby guarantees the enclosure. The surface vertices of the triangular mesh representation are constrained along radial trajectories that are uniformly distributed in 3D angle space. The segmentation is accomplished by determining for each radial trajectory the location of its intersection with the target surface. The surface is first initialized based on an input high confidence boundary image and then resolved progressively based on a dynamic attraction map in an order of decreasing degree of evidence regarding the target surface location. For the visual evaluation, the algorithm achieved acceptable segmentation for 99.35 % vertebral bodies. Quantitative evaluation was performed on 46 vertebral bodies and achieved overall mean Dice coefficient of 0.939 (with max [Formula: see text] 0.957, min [Formula: see text] 0.906 and standard deviation [Formula: see text] 0.011) using manual annotations as the ground truth. Both visual and quantitative evaluations demonstrate encouraging performance of the PSR algorithm. This novel surface resolution strategy provides uniform angular resolution for the segmented surface with computation complexity and runtime that are linearly constrained by the total number of vertices of the triangular mesh representation.

Atypical chemokine receptor ACKR2 controls branching morphogenesis in the developing mammary gland

PubMed Central

Hewit, Kay D.; Pallas, Kenneth J.; Cairney, Claire J.; Lee, Kit M.; Hansell, Christopher A.; Stein, Torsten

2017-01-01

Macrophages are important regulators of branching morphogenesis during development and postnatally in the mammary gland. Regulation of macrophage dynamics during these processes can therefore have a profound impact on development. We demonstrate here that the developing mammary gland expresses high levels of inflammatory CC-chemokines, which are essential in vivo regulators of macrophage migration. We further demonstrate that the atypical chemokine receptor ACKR2, which scavenges inflammatory CC-chemokines, is differentially expressed during mammary gland development. We have previously shown that ACKR2 regulates macrophage dynamics during lymphatic vessel development. Here, we extend these observations to reveal a novel role for ACKR2 in regulating the postnatal development of the mammary gland. Specifically, we show that Ackr2−/− mice display precocious mammary gland development. This is associated with increased macrophage recruitment to the developing gland and increased density of the ductal epithelial network. These data demonstrate that ACKR2 is an important regulator of branching morphogenesis in diverse biological contexts and provide the first evidence of a role for chemokines and their receptors in postnatal development processes. PMID:27888192

TRPP2 ion channels: Critical regulators of organ morphogenesis in health and disease.

PubMed

Busch, Tilman; Köttgen, Michael; Hofherr, Alexis

2017-09-01

Ion channels control the membrane potential and mediate transport of ions across membranes. Archetypical physiological functions of ion channels include processes such as regulation of neuronal excitability, muscle contraction, or transepithelial ion transport. In that regard, transient receptor potential ion channel polycystin 2 (TRPP2) is remarkable, because it controls complex morphogenetic processes such as the establishment of properly shaped epithelial tubules and left-right-asymmetry of organs. The fascinating question of how an ion channel regulates morphogenesis has since captivated the attention of scientists in different disciplines. Four loosely connected key insights on different levels of biological complexity ranging from protein to whole organism have framed our understanding of TRPP2 physiology: 1) TRPP2 is a non-selective cation channel; 2) TRPP2 is part of a receptor-ion channel complex; 3) TRPP2 localizes to primary cilia; and 4) TRPP2 is required for organ morphogenesis. In this review, we will discuss the current knowledge in these key areas and highlight some of the challenges ahead. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Worldwide prevalence and incidence of osteoporotic vertebral fractures.

PubMed

Ballane, G; Cauley, J A; Luckey, M M; El-Hajj Fuleihan, G

2017-05-01

We investigated the prevalence and incidence of vertebral fractures worldwide. We used a systematic Medline search current to 2015 and updated as per authors' libraries. A total of 62 articles of fair to good quality and comparable methods for vertebral fracture identification were considered. The prevalence of morphometric vertebral fractures in European women is highest in Scandinavia (26%) and lowest in Eastern Europe (18%). Prevalence rates in North America (NA) for White women ≥50 are 20-24%, with a White/Black ratio of 1.6. Rates in women ≥50 years in Latin America are overall lower than Europe and NA (11-19%). In Asia, rates in women above ≥65 are highest in Japan (24%), lowest in Indonesia (9%), and in the Middle East, Lebanon, rates are 20%. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Incidence data is less abundant and more heterogeneous. Age-standardized rates in studies combining hospitalized and ambulatory vertebral fractures are highest in South Korea, USA, and Hong Kong and lowest in the UK. Neither a North-South gradient nor a relation to urbanization is evident. Conversely, the incidence of hospitalized vertebral fractures in European patients ≥50 shows a North-South gradient with 3-3.7-fold variability. In the USA, rates in Whites are approximately 4-fold higher than in Blacks. Vertebral fractures variation worldwide is lower than observed with hip fractures, and some of highest rates are unexpectedly from Asia. Better quality representative studies are needed. We investigate the occurrence of vertebral fractures, worldwide, using published data current until the present. Worldwide, the variation in vertebral fractures is lower than observed for hip fractures. Some of the highest rates are from North America and unexpectedly Asia. The highest-lowest ratio between countries, within and across continents, varied from 1.4-2.6. Better quality representative data is needed.

Staff Directory, Department of Vertebrate Zoology, NMNH

Science.gov Websites

Research & Collections About Us Get Involved Calendar Department ofVertebrate Zoology Chestnut Mammals VZ Online Newsletter Visitor Information Research Fellowships Volunteers and Interns VZ Libraries Staff Contact Us NMNH Home › Research & Collections › Vertebrate Zoology › Staff Directory

Sea urchin tooth mineralization: Calcite present early in the aboral plumula

PubMed Central

Stock, Stuart R.; Veis, Arthur; Xiao, Xianghui; Almer, Jonathan D.; Dorvee, Jason R.

2012-01-01

In both vertebrate bone, containing carbonated hydroxyapatite as the mineral phase, and in invertebrate hard tissue comprised of calcium carbonate, a popular view is that the mineral phase develops from a long-lived amorphous precursor which later transforms into crystal form. Important questions linked to this popular view are: When and where is the crystallized material formed, and is amorphous solid added subsequently to the crystalline substrate? Sea urchin teeth, in which the earliest mineral forms within isolated compartments, in a time and position dependent manner, allow direct investigation of the timing of crystallization of the calcite primary plates. Living teeth of the sea urchin Lytechinus variegatus, in their native coelomic fluid, were examined by high-energy synchrotron x-ray diffraction. The diffraction data show that calcite is present in the most aboral portions of the plumula, representing the very earliest stages of mineralization, and that this calcite has the same crystal orientation as in the more mature adoral portions of the same tooth. Raman spectroscopy of the aboral plumula confirms the initial primary plate mineral material is calcite and does not detect amorphous calcium carbonate; in the more mature adoral incisal flange, it does detect a broader calcite peak, consistent with two or more magnesium compositions. We hypothesize that some portion of each syncytial membrane in the plumula provides the information for nucleation of identically oriented calcite crystals that subsequently develop to form the complex geometry of the single crystal sea urchin tooth. PMID:22940703

Gap Junctional Communication in Morphogenesis

PubMed Central

Levin, Michael

2007-01-01

Gap junctions permit the direct passage of small molecules from the cytosol of one cell to that of its neighbor, and thus form a system of cell-cell communication that exists alongside familiar secretion/receptor signaling. Because of the rich potential for regulation of junctional conductance, and directional and molecular gating (specificity), gap junctional communication (GJC) plays a crucial role in many aspects of normal tissue physiology. However, the most exciting role for GJC is in the regulation of information flow that takes place during embryonic development, regeneration, and tumor progression. The molecular mechanisms by which GJC establishes local and long-range instructive morphogenetic cues are just beginning to be understood. This review summarizes the current knowledge of the involvement of GJC in the patterning of both vertebrate and invertebrate systems and discusses in detail several morphogenetic systems in which the properties of this signaling have been molecularly characterized. One model consistent with existing data in the fields of vertebrate left-right patterning and anterior-posterior polarity in flatworm regeneration postulates electrophoretically-guided movement of small molecule morphogens through long-range GJC paths. The discovery of mechanisms controlling embryonic and regenerative GJC-mediated signaling, and identification of the downstream targets of GJC-permeable molecules, represent exciting next areas of research in this fascinating field. PMID:17481700

Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.

PubMed

Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Huang, Yihe; Ma, Yan; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

2016-06-01

The Col1a2(+/G610C) knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2(+/G610C) and their wild-type controls (Col1a2(+/+)), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2(+/G610C) with an LRP(+/A214V) high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2(+/G610C) tibias had 13% fewer secondary trabeculae than Col1a2(+/+), these were thinner (11%) and more widely spaced (20%) than those of Col1a2(+/+) mice. Vertebrae of Col1a2(+/G610C) mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1(a2+/+). The cortical bone of Col1a2(+/G610C) tibias at 2-months had 3% higher tissue mineral density compared to Col1a2(+/+); Col1a2(+/G610C) vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2(+/+). FTIRI analysis, which provides information on bone chemical composition at ~7μm-spatial resolution, showed tibias at 10-days did not differ between genotypes. Comparing identical bone types in Col1a2(+/G610C) to Col1a2(+/+) at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2(+/G610C) vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution

The development and morphogenesis of the tendon-to-bone insertion What development can teach us about healing

PubMed Central

Thomopoulos, Stavros; Genin, Guy M.; Galatz, Leesa M.

2013-01-01

The attachment of dissimilar materials is a major challenge because of the high levels of stress that develop at such interfaces. An effective solution to this problem develops at the attachment of tendon (a compliant “soft tissue”) to bone (a stiff “hard tissue”). This tissue, the “enthesis”, transitions from tendon to bone through gradations in structure, composition, and mechanical properties. These gradations are not regenerated during tendon-to-bone healing, leading to a high incidence of failure after surgical repair. Understanding the development of the enthesis may allow scientists to develop treatments that regenerate the natural tendon-to-bone insertion. Recent work has demonstrated that both biologic and mechanical factors drive the development and morphogenesis of the enthesis. A cascade of biologic signals similar to those seen in the growth plate promotes mineralization of cartilage on the bony end of the enthesis and the formation of fibrocartilage on the tendon end of the enthesis. Mechanical loading is also necessary for the development of the enthesis. Removal of muscle load impairs the formation of bone, fibrocartilage, and tendon at the developing enthesis. This paper reviews recent work on the development of the enthesis, with an emphasis on the roles of biologic and mechanical factors. PMID:20190378

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

An invertebrate stomach's view on vertebrate ecology: certain invertebrates could be used as "vertebrate samplers" and deliver DNA-based information on many aspects of vertebrate ecology.

PubMed

Calvignac-Spencer, Sébastien; Leendertz, Fabian H; Gilbert, M Thomas P; Schubert, Grit

2013-11-01

Recent studies suggest that vertebrate genetic material ingested by invertebrates (iDNA) can be used to investigate vertebrate ecology. Given the ubiquity of invertebrates that feed on vertebrates across the globe, iDNA might qualify as a very powerful tool for 21st century population and conservation biologists. Here, we identify some invertebrate characteristics that will likely influence iDNA retrieval and elaborate on the potential uses of invertebrate-derived information. We hypothesize that beyond inventorying local faunal diversity, iDNA should allow for more profound insights into wildlife population density, size, mortality, and infectious agents. Based on the similarities of iDNA with other low-quality sources of DNA, a general technical framework for iDNA analyses is proposed. As it is likely that no such thing as a single ideal iDNA sampler exists, forthcoming research efforts should aim at cataloguing invertebrate properties relevant to iDNA retrieval so as to guide future usage of the invertebrate tool box. © 2013 WILEY Periodicals, Inc.

iDNA screening: Disease vectors as vertebrate samplers.

PubMed

Kocher, Arthur; de Thoisy, Benoit; Catzeflis, François; Valière, Sophie; Bañuls, Anne-Laure; Murienne, Jérôme

2017-11-01

In the current context of global change and human-induced biodiversity decline, there is an urgent need for developing sampling approaches able to accurately describe the state of biodiversity. Traditional surveys of vertebrate fauna involve time-consuming and skill-demanding field methods. Recently, the use of DNA derived from invertebrate parasites (leeches and blowflies) was suggested as a new tool for vertebrate diversity assessment. Bloodmeal analyses of arthropod disease vectors have long been performed to describe their feeding behaviour, for epidemiological purposes. On the other hand, this existing expertise has not yet been applied to investigate vertebrate fauna per se. Here, we evaluate the usefulness of hematophagous dipterans as vertebrate samplers. Blood-fed sand flies and mosquitoes were collected in Amazonian forest sites and analysed using high-throughput sequencing of short mitochondrial markers. Bloodmeal identifications highlighted contrasting ecological features and feeding behaviour among dipteran species, which allowed unveiling arboreal and terrestrial mammals of various body size, as well as birds, lizards and amphibians. Additionally, lower vertebrate diversity was found in sites undergoing higher levels of human-induced perturbation. These results suggest that, in addition to providing precious information on disease vector host use, dipteran bloodmeal analyses may represent a useful tool in the study of vertebrate communities. Although further effort is required to validate the approach and consider its application to large-scale studies, this first work opens up promising perspectives for biodiversity monitoring and eco-epidemiology. © 2017 John Wiley & Sons Ltd.

Evolution of the vertebrate phototransduction cascade activation steps.

PubMed

Lamb, Trevor D; Hunt, David M

2017-11-01

We examine the molecular phylogeny of the proteins underlying the activation steps of vertebrate phototransduction, for both agnathan and jawed vertebrate taxa. We expand the number of taxa analysed and we update the alignment and tree building methodology from a previous analysis. For each of the four primary components (the G-protein transducin alpha subunit, Gα T , the cyclic GMP phosphodiesterase, PDE6, and the alpha and beta subunits of the cGMP-gated ion channel, CNGC), the phylogenies appear consistent with expansion from an ancestral proto-vertebrate cascade during two rounds of whole-genome duplication followed by divergence of the agnathan and jawed vertebrate lineages. In each case, we consider possible scenarios for the underlying gene duplications and losses, and we apply relevant constraints to the tree construction. From tests of the topology of the resulting trees, we obtain a scenario for the expansion of each component during 2R that accurately fits the observations. Similar analysis of the visual opsins indicates that the only expansion to have occurred during 2R was the formation of Rh1 and Rh2. Finally, we propose a hypothetical scenario for the conversion of an ancestral chordate cascade into the proto-vertebrate phototransduction cascade, prior to whole-genome duplication. Together, our models provide a plausible account for the origin and expansion of the vertebrate phototransduction cascade. Copyright © 2017 Elsevier Inc. All rights reserved.

CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling.

PubMed

Chen, Qian; Zhu, Yong-Chuan; Yu, Jing; Miao, Sheng; Zheng, Jing; Xu, Li; Zhou, Yang; Li, Dan; Zhang, Chi; Tao, Jiong; Xiong, Zhi-Qi

2010-09-22

Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.

Regulation of tight junction assembly and epithelial morphogenesis by the heat shock protein Apg-2

PubMed Central

Aijaz, Saima; Sanchez-Heras, Elena; Balda, Maria S; Matter, Karl

2007-01-01

Background Tight junctions are required for epithelial barrier formation and participate in the regulation of signalling mechanisms that control proliferation and differentiation. ZO-1 is a tight junction-associated adaptor protein that regulates gene expression, junction assembly and epithelial morphogenesis. We have previously demonstrated that the heat shock protein Apg-2 binds ZO-1 and thereby regulates its role in cell proliferation. Here, we addressed the question whether Apg-2 is also important for junction formation and epithelial morphogenesis. Results We demonstrate that depletion of Apg-2 by RNAi in MDCK cells did not prevent formation of functional tight junctions. Similar to ZO-1, however, reduced expression of Apg-2 retarded de novo junction assembly if analysed in a Ca-switch model. Formation of functional junctions, as monitored by measuring transepithelial electrical resistance, and recruitment of tight and adherens junction markers were retarded. If cultured in three dimensional extracellular matrix gels, Apg-2 depleted cells, as previously shown for ZO-1 depleted cells, did not form hollow polarised cysts but poorly organised, irregular structures. Conclusion Our data indicate that Apg-2 regulates junction assembly and is required for normal epithelial morphogenesis in a three-dimensional culture system, suggesting that Apg-2 is an important regulator of epithelial differentiation. As the observed phenotypes are similar to those previously described for ZO-1 depleted cells and depletion of Apg-2 retards junctional recruitment of ZO-1, regulation of ZO-1 is likely to be an important functional role for Apg-2 during epithelial differentiation. PMID:18028534

Regulation of tight junction assembly and epithelial morphogenesis by the heat shock protein Apg-2.

PubMed

Aijaz, Saima; Sanchez-Heras, Elena; Balda, Maria S; Matter, Karl

2007-11-20

Tight junctions are required for epithelial barrier formation and participate in the regulation of signalling mechanisms that control proliferation and differentiation. ZO-1 is a tight junction-associated adaptor protein that regulates gene expression, junction assembly and epithelial morphogenesis. We have previously demonstrated that the heat shock protein Apg-2 binds ZO-1 and thereby regulates its role in cell proliferation. Here, we addressed the question whether Apg-2 is also important for junction formation and epithelial morphogenesis. We demonstrate that depletion of Apg-2 by RNAi in MDCK cells did not prevent formation of functional tight junctions. Similar to ZO-1, however, reduced expression of Apg-2 retarded de novo junction assembly if analysed in a Ca-switch model. Formation of functional junctions, as monitored by measuring transepithelial electrical resistance, and recruitment of tight and adherens junction markers were retarded. If cultured in three dimensional extracellular matrix gels, Apg-2 depleted cells, as previously shown for ZO-1 depleted cells, did not form hollow polarised cysts but poorly organised, irregular structures. Our data indicate that Apg-2 regulates junction assembly and is required for normal epithelial morphogenesis in a three-dimensional culture system, suggesting that Apg-2 is an important regulator of epithelial differentiation. As the observed phenotypes are similar to those previously described for ZO-1 depleted cells and depletion of Apg-2 retards junctional recruitment of ZO-1, regulation of ZO-1 is likely to be an important functional role for Apg-2 during epithelial differentiation.

Evolution of vertebrate sex chromosomes and dosage compensation.

PubMed

Graves, Jennifer A Marshall

2016-01-01

Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

Incidence of Vertebral Fractures in Women with Systemic Lupus Erythematosus After 8 Years of Follow-Up.

PubMed

García-Carrasco, Mario; Mendoza-Pinto, Claudia; León-Vázquez, María de la Luz; Méndez-Martínez, Socorro; Etchegaray-Morales, Ivet; Montiel-Jarquín, Álvaro; Enriquez-Guerra, Miguel Angel; Muñóz-Guarneros, Margarita; Gálvez-Romero, José Luis; Soto-Santillán, Pamela; Cervera, Ricard

2017-09-01

The aim of this study was to evaluate possible associations between potential risk factors and the occurrence of established vertebral fractures (VF) in Mexican patients with systemic lupus erythematosus (SLE). Consecutive patients with SLE were enrolled in a prospective, observational study from 2006 to 2015. Information on potential risk factors, including demographics, clinical data, and bone mineral density (BMD) at the lumbar spine and hip on dual-energy X-ray absorptiometry was collected at baseline and follow-up. Semiquantitative analysis was used to determine incident VF on lateral thoracic and lumbar radiographs, defined as any vertebral body graded normal at baseline and at least mildly deformed (20-25% reduction or more in any vertebral height) during follow-up. Differences in baseline characteristics were assessed in patients with and without new radiographic VF. Of 110 SLE patients included, with a median follow-up of 8 (IQR 8-9) years, 22 (20%) had radiographic VF at baseline; 35 (32%) patients had a new VF. The annual incidence rate of new morphometric VF was 3.5 (95% CI 2.4-4.91) per 100 patient/years. Most fractures were mild or moderate and biconcave shaped. Incident VF were significantly associated with baseline BMD at the total hip and longer disease duration. Cumulative glucocorticoid dose, postmenopausal status, and previous prevalent VF were not associated with VF. In this SLE cohort in daily clinical practice, new VF were frequently present in SLE patients, especially those with longer disease duration and low-hip BMD.

Apatite mineralization in elasmobranch skeletons via a polyphosphate intermediate

NASA Astrophysics Data System (ADS)

Omelon, Sidney; Lacroix, Nicolas; Lildhar, Levannia; Variola, Fabio; Dean, Mason

2014-05-01

All vertebrate skeletons are stiffened with apatite, a calcium phosphate mineral. Control of apatite mineralization is essential to the growth and repair of the biology of these skeletons, ensuring that apatite is deposited in the correct tissue location at the desired time. The mechanism of this biochemical control remains debated, but must involve increasing the localized apatite saturation state. It was theorized in 1923 that alkaline phosphatase (ALP) activity provides this control mechanism by increasing the inorganic phosphate (Pi) concentration via dephosphorylation of phosphorylated molecules. The ALP substrate for biological apatite is not known. We propose that polyphosphates (polyPs) produced by mitochondria may be the substrate for biological apatite formation by ALP activity. PolyPs (PO3-)n, also known as condensed phosphates, represent a concentrated, bioavailable Pi-storage strategy. Mitochondria import Pi and synthesize phosphate polymers through an unknown biochemical mechanism. When chelated with calcium and/or other cations, the effective P-concentration of these neutrally charged, amorphous, polyP species can be very high (~ 0.5 M), without inducing phosphate mineral crystallization. This P-concentration in the low Pi-concentration biological environment offers a method of concentrating P well above an apatite supersaturation required for nucleation. Bone is the most studied mineralized skeletal tissue. However, locating and analyzing active mineralizing areas is challenging. We studied calcified cartilage skeletons of elasmobranch fishes (sharks, stingrays and relatives) to analyse the phosphate chemistry in this continually mineralizing skeleton. Although the majority of the elasmobranch skeleton is unmineralized cartilage, it is wrapped in an outer layer of mineralized tissue comprised of small tiles called tesserae. These calcified tesserae continually grow through the formation of new mineral on their borders. Co-localization of ALP and

Ancient duplications and functional divergence in the interferon regulatory factors of vertebrates provide insights into the evolution of vertebrate immune systems.

PubMed

Du, Kang; Zhong, Zaixuan; Fang, Chengchi; Dai, Wei; Shen, Yanjun; Gan, Xiaoni; He, Shunping

2018-04-01

Interferon regulatory factors (IRFs) were first discovered as transcription factors that regulate the transcription of human interferon (IFN)-β. Increasing evidence shows that they might be important players involved in Adaptive immune system (AIS) evolution. Although numbers of IRFs have been identified in chordates, the evolutionary history and functional diversity of this gene family during the early evolution of vertebrates have remained obscure. Using IRF HMM profile and HMMER searches, we identified 148 IRFs in 11 vertebrates and 4 protochordates. For them, we reconstructed the phylogenetic relationships, determined the synteny conservation, investigated the profile of natural selection, and analyzed the expression patterns in four "living fossil" vertebrates: lamprey, elephant shark, coelacanth and bichir. The results from phylogeny and synteny analysis imply that vertebrate IRFs evolved from three predecessors, instead of four as suggested in a previous study, as results from an ancient duplication followed by special expansions and lost during the vertebrate evolution. The profile of natural selection and expression reveals functional dynamics during the process. Together, they suggest that the 2nd whole-genome duplication (2WGD) provided raw materials for innovation in the IRF family, and that the birth of type-I IFN might be an important factor inducing the establishment of IRF-mediated immune networks. As a member involved in the AIS evolution, IRF provide insights into the process and mechanism involved in the complexity and novelties of vertebrate immune systems. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Distinct Recruitment and Function of Gab1 and Gab2 in Met Receptor-mediated Epithelial Morphogenesis

PubMed Central

Lock, Lisa S.; Maroun, Christiane R.; Naujokas, Monica A.; Park, Morag

2002-01-01

The Gab family of docking proteins (Gab1 and Gab2) are phosphorylated in response to various cytokines and growth factors. Gab1 acts to diversify the signal downstream from the Met receptor tyrosine kinase through the recruitment of multiple signaling proteins, and is essential for epithelial morphogenesis. To determine whether Gab1 and Gab2 are functionally redundant, we have examined the role of Gab2 in epithelial cells. Both Gab1 and Gab2 are expressed in epithelial cells and localize to cell-cell junctions. However, whereas overexpression of Gab1 promotes a morphogenic response, the overexpression of Gab2 fails to induce this response. We show that Gab2 recruitment to the Met receptor is dependent on the Grb2 adapter protein. In contrast, Gab1 recruitment to Met is both Grb2 dependent and Grb2 independent. The latter requires a novel amino acid sequence present in the Met-binding domain of Gab1 but not Gab2. Mutation of these residues in Gab1 impairs both association with the Met receptor and the ability of Gab1 to promote a morphogenic response, whereas their insertion into Gab2 increases Gab2 association with Met, but does not confer on Gab2 the ability to promote epithelial morphogenesis. We propose that the Grb2-independent recruitment of Gab proteins to Met is necessary but not sufficient to promote epithelial morphogenesis. PMID:12058075

Calcium signals act through histone deacetylase to mediate pronephric kidney morphogenesis.

PubMed

Rothschild, Sarah C; Lee, Hunter J; Ingram, Sarah R; Mohammadi, Daniel K; Walsh, Gregory S; Tombes, Robert M

2018-06-01

Autosomal dominant polycystic kidney disease is the most common monogenetic kidney disorder and is linked to mutations in PKD1 and PKD2. PKD2, a Ca 2+ -conducting TRP channel enriched in ciliated cells and gated by extracellular signals, is necessary to activate the multifunctional Ca 2+/ calmodulin-dependent protein kinase type 2 (CaMK-II), enabling kidney morphogenesis and cilia stability. In this study, antisense morpholino oligonucleotides and pharmacological compounds were employed to investigate the roles of class II HDAC family members (HDAC 4, 5, and 6) in Zebrafish kidney development. While all three class II HDAC genes were expressed throughout the embryo during early development, HDAC5-morphant embryos exhibited anterior cysts and destabilized cloacal cilia, similar to PKD2 and CaMK-II morphants. In contrast, HDAC4-morphant embryos exhibited elongated cloacal cilia and lacked anterior kidney defects. Suppression of HDAC4 partially reversed the cilia shortening and anterior convolution defects caused by CaMK-II deficiency, whereas HDAC5 loss exacerbated these defects. EGFP-HDAC4, but not EGFP-HDAC5, translocated into the nucleus upon CaMK-II suppression in pronephric kidney cells. These results support a model by which activated CaMK-II sequesters HDAC4 in the cytosol to enable primary cilia formation and kidney morphogenesis. Developmental Dynamics 247:807-817, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Use of cervical vertebral dimensions for assessment of children growth.

PubMed

Caldas, Maria de Paula; Ambrosano, Gláucia Maria Bovi; Haiter-Neto, Francisco

2007-04-01

The purpose of this study was to investigate whether skeletal maturation using cephalometric radiographs could be used in a Brazilian population. The study population was selected from the files of the Oral Radiological Clinic of the Dental School of Piracicaba, Brazil and consisted of 128 girls and 110 boys (7.0 to 15.9 years old) who had cephalometric and hand-wrist radiographs taken on the same day. Cervical vertebral bone age was evaluated using the method described by Mito and colleagues in 2002. Bone age was assessed by the Tanner-Whitehouse (TW3) method and was used as a gold standard to determine the reliability of cervical vertebral bone age. An analysis of variance and Tukey's post-hoc test were used to compare cervical vertebral bone age, bone age and chronological age at 5% significance level. The analysis of the Brazilian female children data showed that there was a statistically significant difference (p<0.05) between cervical vertebral bone age and chronological age and between bone age and chronological age. However no statistically significant difference (p>0.05) was found between cervical vertebral bone age and bone age. Differently, the analysis of the male children data revealed a statistically significant difference (p<0.05) between cervical vertebral bone age and bone age and between cervical vertebral bone age and chronological age (p<0.05). The findings of the present study suggest that the method for objectively evaluating skeletal maturation on cephalometric radiographs by determination of vertebral bone age can be applied to Brazilian females only. The development of a new method to objectively evaluate cervical vertebral bone age in males is needed.

Evolutionary growth process of highly conserved sequences in vertebrate genomes.

PubMed

Ishibashi, Minaka; Noda, Akiko Ogura; Sakate, Ryuichi; Imanishi, Tadashi

2012-08-01

Genome sequence comparison between evolutionarily distant species revealed ultraconserved elements (UCEs) among mammals under strong purifying selection. Most of them were also conserved among vertebrates. Because they tend to be located in the flanking regions of developmental genes, they would have fundamental roles in creating vertebrate body plans. However, the evolutionary origin and selection mechanism of these UCEs remain unclear. Here we report that UCEs arose in primitive vertebrates, and gradually grew in vertebrate evolution. We searched for UCEs in two teleost fishes, Tetraodon nigroviridis and Oryzias latipes, and found 554 UCEs with 100% identity over 100 bps. Comparison of teleost and mammalian UCEs revealed 43 pairs of common, jawed-vertebrate UCEs (jUCE) with high sequence identities, ranging from 83.1% to 99.2%. Ten of them retain lower similarities to the Petromyzon marinus genome, and the substitution rates of four non-exonic jUCEs were reduced after the teleost-mammal divergence, suggesting that robust conservation had been acquired in the jawed vertebrate lineage. Our results indicate that prototypical UCEs originated before the divergence of jawed and jawless vertebrates and have been frozen as perfect conserved sequences in the jawed vertebrate lineage. In addition, our comparative sequence analyses of UCEs and neighboring regions resulted in a discovery of lineage-specific conserved sequences. They were added progressively to prototypical UCEs, suggesting step-wise acquisition of novel regulatory roles. Our results indicate that conserved non-coding elements (CNEs) consist of blocks with distinct evolutionary history, each having been frozen since different evolutionary era along the vertebrate lineage. Copyright © 2012 Elsevier B.V. All rights reserved.

Evolution of the β-adrenoreceptors in vertebrates.

PubMed

Zavala, Kattina; Vandewege, Michael W; Hoffmann, Federico G; Opazo, Juan C

2017-01-01

The study of the evolutionary history of genes related to human disease lies at the interface of evolution and medicine. These studies provide the evolutionary context on which medical researchers should work, and are also useful in providing information to suggest further genetic experiments, especially in model species where genetic manipulations can be made. Here we studied the evolution of the β-adrenoreceptor gene family in vertebrates with the aim of adding an evolutionary framework to the already abundant physiological information. Our results show that in addition to the three already described vertebrate β-adrenoreceptor genes there is an additional group containing cyclostome sequences. We suggest that β-adrenoreceptors diversified as a product of the two whole genome duplications that occurred in the ancestor of vertebrates. Gene expression patterns are in general consistent across species, suggesting that expression dynamics were established early in the evolutionary history of vertebrates, and have been maintained since then. Finally, amino acid polymorphisms that are associated to pathological conditions in humans appear to be common in non-human mammals, suggesting that the phenotypic effects of these mutations depend on epistatic interaction with other positions. The evolutionary analysis of the β-adrenoreceptors delivers new insights about the diversity of these receptors in vertebrates, the evolution of the expression patterns and a comparative perspective regarding the polymorphisms that in humans are linked to pathological conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Amorphous calcium carbonate controls avian eggshell mineralization: A new paradigm for understanding rapid eggshell calcification.

PubMed

Rodríguez-Navarro, Alejandro B; Marie, Pauline; Nys, Yves; Hincke, Maxwell T; Gautron, Joel

2015-06-01

Avian eggshell mineralization is the fastest biogenic calcification process known in nature. How this is achieved while producing a highly crystalline material composed of large calcite columnar single crystals remains largely unknown. Here we report that eggshell mineral originates from the accumulation of flat disk-shaped amorphous calcium carbonate (ACC) particles on specific organic sites on the eggshell membrane, which are rich in proteins and sulfated proteoglycans. These structures known as mammillary cores promote the nucleation and stabilization of a amorphous calcium carbonate with calcitic short range order which predetermine the calcite composition of the mature eggshell. The amorphous nature of the precursor phase was confirmed by the diffuse scattering of X-rays and electrons. The nascent calcitic short-range order of this transient mineral phase was revealed by infrared spectroscopy and HRTEM. The ACC mineral deposited around the mammillary core sites progressively transforms directly into calcite crystals without the occurrence of any intermediate phase. Ionic speciation data suggest that the uterine fluid is equilibrated with amorphous calcium carbonate, throughout the duration of eggshell mineralization process, supporting that this mineral phase is constantly forming at the shell mineralization front. On the other hand, the transient amorphous calcium carbonate mineral deposits, as well as the calcite crystals into which they are converted, form by the ordered aggregation of nanoparticles that support the rapid mineralization of the eggshell. The results of this study alter our current understanding of avian eggshell calcification and provide new insights into the genesis and formation of calcium carbonate biominerals in vertebrates. Copyright © 2015 Elsevier Inc. All rights reserved.

Mineralization of collagen may occur on fibril surfaces: evidence from conventional and high-voltage electron microscopy and three-dimensional imaging

NASA Technical Reports Server (NTRS)

Landis, W. J.; Hodgens, K. J.; Song, M. J.; Arena, J.; Kiyonaga, S.; Marko, M.; Owen, C.; McEwen, B. F.

1996-01-01

The interaction between collagen and mineral crystals in the normally calcifying leg tendons from the domestic turkey, Meleagris gallopavo, has been investigated at an ultrastructural level with conventional and high-voltage electron microscopy, computed tomography, and three-dimensional image reconstruction methods. Specimens treated by either aqueous or anhydrous techniques and resin-embedded were appropriately sectioned and regions of early tendon mineralization were photographed. On the basis of individual photomicrographs, stereoscopic pairs of images, and tomographic three-dimensional image reconstructions, platelet-shaped crystals may be demonstrated for the first time in association with the surface of collagen fibrils. Mineral is also observed in closely parallel arrays within collagen hole and overlap zones. The mineral deposition at these spatially distinct locations in the tendon provides insight into possible means by which calcification is mediated by collagen as a fundamental event in skeletal and dental formation among vertebrates.

Gravidity, Parity and Vertebral Dimensions in the Northern Finland Birth Cohort 1966.

PubMed

Oura, Petteri; Paananen, Markus; Auvinen, Juha; Niinimäki, Jaakko; Niinimäki, Maarit; Karppinen, Jaro; Junno, Juho-Antti

2018-03-15

A population-based birth cohort study. To investigate the association between gravidity, parity and vertebral geometry among middle-aged women. Vertebral size is a recognized determinant of vertebral fracture risk. Yet only a few lifestyle factors that influence vertebral size are known. Pregnancy is a labile period which may affect the maternal vertebral size or shape. The lumbar lordosis angle is permanently deepened by pregnancy, but it remains unclear whether vertebral shape or size contribute to this deepened angle. We aimed to investigate whether gravidity and parity were associated with vertebral cross-sectional area (CSA) and height ratio (anterior height: posterior height) among 705 middle-aged women from the Northern Finland Birth Cohort 1966. We measured the corpus of their fourth lumbar vertebra using magnetic resonance imaging of the lumbar spine at the age of 46. Gravidity and parity were elicited using a questionnaire also at the age of 46. Linear regression analysis was used with adjustments for body mass index, vertebral CSA (height ratio models), and vertebral height (CSA models). We also ran a subgroup analysis which did not include nulliparous women, and we compared nulliparous women with grand multiparous women. The models found no statistically significant associations between the predictors and outcomes. Crude and adjusted results were highly similar, and the subgroup analyses provided analogous results. Pregnancy, or even multiple pregnancies, do not seem to have long-term effects on vertebral geometry. In order to enhance the prevention of vertebral fractures, future studies should aim to reveal more lifestyle determinants of vertebral size. 3.

Involvement of actin filaments in rhizoid morphogenesis of Spirogyra.

PubMed

Yoshida, Katsuhisa; Shimmen, Teruo

2009-01-01

The role of actin filaments in rhizoid morphogenesis was studied in Spirogyra. When the algal filaments were severed, new terminal cells started tip growth and finally formed rhizoids. Actin inhibitors, latrunculin B and cytochalasin D, reversibly inhibited the process. A mesh-like structure of actin filaments (AFs) was formed at the tip region. Gd(3+) inhibited tip growth and decreased AFs in the tip region. Either a decrease in turgor pressure or lowering of the external Ca(2+) concentration also induced similar results. It was suggested that the mesh-like AF structure is indispensable for the elongation of rhizoids. A possible organization mechanism of the mesh-like AF structure was discussed.

Gout and the Risk of Non-vertebral Fracture

PubMed Central

Kim, Seoyoung C.; Paik, Julie M.; Liu, Jun; Curhan, Gary C.; Solomon, Daniel H.

2016-01-01

Prior studies suggest an association between osteoporosis, systemic inflammation and pro-inflammatory cytokines such as IL-1 and IL-6. Conflicting findings exist on the association between hyperuricemia and osteoporosis. Furthermore, it remains unknown whether gout, a common inflammatory arthritis, affects fracture risk. Using data from a US commercial health plan (2004–2013), we evaluated the risk of non-vertebral fracture (i.e. forearm, wrist, hip and pelvis) in patients with gout versus those without. Gout patients were identified with ≥2 diagnosis codes and ≥1 dispensing for a gout-related drug. Non-gout patients, identified with ≥2 visits coded for any diagnosis and ≥1 dispensing for any prescription drugs, were free of gout diagnosis and received no gout-related drugs. Hip fracture was the secondary outcome. Fractures were identified with a combination of diagnosis and procedure codes. Cox proportional hazards models compared the risk of non-vertebral fracture in gout patients versus non-gout, adjusting for over 40 risk factors for osteoporotic fracture. Among gout patients with baseline serum uric acid (sUA) measurements available, we assessed the risk of non-vertebral fracture associated with sUA. We identified 73,202 gout and 219,606 non-gout patients, matched on age, sex, and the date of study entry. The mean age was 60 years and 82% were men. Over the mean 2-year follow-up, the incidence rate of non-vertebral fracture per 1,000 person-years was 2.92 in gout and 2.66 in non-gout. The adjusted hazard ratio (HR) was 0.98 (95%CI 0.85–1.12) for non-vertebral fracture and 0.83 (95%CI 0.65–1.07) for hip fracture in gout versus non-gout. Subgroup analysis (n=15,079) showed no association between baseline sUA and non-vertebral fracture (HR 1.03, 95%CI 0.93–1.15), adjusted for age, sex, comorbidity score and number of any prescription drugs. Gout was not associated with a risk of non-vertebral fracture. Among patients with gout, sUA was not

[Vertebral artery dissection due to the C6 transverse process and laryngeal cartilage associated with vertebral artery anomaly].

PubMed

Kusunoki Nakamoto, Fumiko; Hashimoto Maeda, Meiko; Mori, Kentaro; Hara, Takayuki; Uesaka, Yoshikazu

2014-01-01

A 52-year-old woman complained of the sudden onset of a left temporal headache, left neck stiffness and dizziness. Brain magnetic resonance imaging showed a high-intensity lesion in the right medial medulla. Dynamic cerebral angiography revealed vertebral artery dissection and compression at the C6 level due to a transverse process at the C6 level associated with rightward head rotation. Removal of bone and decompression of the vertebral artery were performed from the C5 to C6 levels. Intraoperasively, obstruction of blood flow due to a laryngeal cartilage that rotated with the passive rotation of the patient's head to the right was found. To the best of our knowledge this is the first reported case of vertebral artery occlusion due to a laryngeal cartilage associated with head rotation.

Bone Mineral Density in Relation to Metabolic Syndrome Components in Postmenopausal Women With Diabetes Mellitus Type 2

PubMed

Bilić-Ćurčić, Ines; Makarović, Sandra; Mihaljević, Ivan; Franceschi, Maja; Jukić, Tomislav

2017-03-01

Diabetes mellitus type 2 is associated with greater bone mineral density (BMD) due to obesity, although rapid bone loss observed over time could be explained by elevated chronic inflammation. The objective of this study was to investigate the relationship between central adiposity and hyperinsulinemia, as well as inflammation markers with vertebral and femoral BMD and bone turnover markers in postmenopausal women with type 2 diabetes. Femoral and vertebral BMD, osteocalcin, pyrilinks D, beta-CrossLaps (B-CTx), insulin, C-reactive protein (CRP), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) were measured in 114 postmenopausal female patients with diabetes type 2. The patients of similar age, HbA1c levels and diabetes duration were divided into 2 groups based on their body mass index (BMI) values: lower or equal to 27 kg/m(2) (31 patients) and higher than 27 kg/m(2) (83 patients). Lower levels of osteocalcin (p=0.001), B-CTx (p=0.000007) and pyrilinks D (p=0.0365), and higher femoral BMD (p=0.00006), insulin level (p=0.0002), PAI-1 (p=0.00000) and CRP (p=0.002) were found in the overweight group. There were no signifi cant differences in vertebral BMD and fibrinogen. Osteocalcin and B-CTx showed inverse correlation, and femoral BMD positive correlation with waist circumference, insulin level and PAI-1. This suggests that abdominal obesity and hyperinsulinemia as components of the metabolic syndrome could increase femoral BMD by lowering bone rate. In addition, the only inflammation marker linked with femoral BMD was PAI-1, which is associated with increased mineralization of cortical bone in mouse.

Contact Us, Department of Vertebrate Zoology, NMNH

Science.gov Websites

Contact Us NMNH Home › Research & Collections › Vertebrate Zoology › Contact Us Contacting Individual Staff Members: To contact members of the Department of Vertebrate Zoology please go to the Staff page. Most members will be linked to their own webpage that contains contact information, research

Extensive Use of RNA-Binding Proteins in Drosophila Sensory Neuron Dendrite Morphogenesis

PubMed Central

Olesnicky, Eugenia C.; Killian, Darrell J.; Garcia, Evelyn; Morton, Mary C.; Rathjen, Alan R.; Sola, Ismail E.; Gavis, Elizabeth R.

2013-01-01

The large number of RNA-binding proteins and translation factors encoded in the Drosophila and other metazoan genomes predicts widespread use of post-transcriptional regulation in cellular and developmental processes. Previous studies identified roles for several RNA-binding proteins in dendrite branching morphogenesis of Drosophila larval sensory neurons. To determine the larger contribution of post-transcriptional gene regulation to neuronal morphogenesis, we conducted an RNA interference screen to identify additional Drosophila proteins annotated as either RNA-binding proteins or translation factors that function in producing the complex dendritic trees of larval class IV dendritic arborization neurons. We identified 88 genes encoding such proteins whose knockdown resulted in aberrant dendritic morphology, including alterations in dendritic branch number, branch length, field size, and patterning of the dendritic tree. In particular, splicing and translation initiation factors were associated with distinct and characteristic phenotypes, suggesting that different morphogenetic events are best controlled at specific steps in post-transcriptional messenger RNA metabolism. Many of the factors identified in the screen have been implicated in controlling the subcellular distributions and translation of maternal messenger RNAs; thus, common post-transcriptional regulatory strategies may be used in neurogenesis and in the generation of asymmetry in the female germline and embryo. PMID:24347626

Global analysis of gene expression in mineralizing fish vertebra-derived cell lines: new insights into anti-mineralogenic effect of vanadate

PubMed Central

2011-01-01

Background Fish has been deemed suitable to study the complex mechanisms of vertebrate skeletogenesis and gilthead seabream (Sparus aurata), a marine teleost with acellular bone, has been successfully used in recent years to study the function and regulation of bone and cartilage related genes during development and in adult animals. Tools recently developed for gilthead seabream, e.g. mineralogenic cell lines and a 4 × 44K Agilent oligo-array, were used to identify molecular determinants of in vitro mineralization and genes involved in anti-mineralogenic action of vanadate. Results Global analysis of gene expression identified 4,223 and 4,147 genes differentially expressed (fold change - FC > 1.5) during in vitro mineralization of VSa13 (pre-chondrocyte) and VSa16 (pre-osteoblast) cells, respectively. Comparative analysis indicated that nearly 45% of these genes are common to both cell lines and gene ontology (GO) classification is also similar for both cell types. Up-regulated genes (FC > 10) were mainly associated with transport, matrix/membrane, metabolism and signaling, while down-regulated genes were mainly associated with metabolism, calcium binding, transport and signaling. Analysis of gene expression in proliferative and mineralizing cells exposed to vanadate revealed 1,779 and 1,136 differentially expressed genes, respectively. Of these genes, 67 exhibited reverse patterns of expression upon vanadate treatment during proliferation or mineralization. Conclusions Comparative analysis of expression data from fish and data available in the literature for mammalian cell systems (bone-derived cells undergoing differentiation) indicate that the same type of genes, and in some cases the same orthologs, are involved in mechanisms of in vitro mineralization, suggesting their conservation throughout vertebrate evolution and across cell types. Array technology also allowed identification of genes differentially expressed upon exposure of fish cell lines to vanadate

The generation of vertebral segmental patterning in the chick embryo

PubMed Central

Senthinathan, Biruntha; Sousa, Cátia; Tannahill, David; Keynes, Roger

2012-01-01

We have carried out a series of experimental manipulations in the chick embryo to assess whether the notochord, neural tube and spinal nerves influence segmental patterning of the vertebral column. Using Pax1 expression in the somite-derived sclerotomes as a marker for segmentation of the developing intervertebral disc, our results exclude such an influence. In contrast to certain teleost species, where the notochord has been shown to generate segmentation of the vertebral bodies (chordacentra), these experiments indicate that segmental patterning of the avian vertebral column arises autonomously in the somite mesoderm. We suggest that in amniotes, the subdivision of each sclerotome into non-miscible anterior and posterior halves plays a critical role in establishing vertebral segmentation, and in maintaining left/right alignment of the developing vertebral elements at the body midline. PMID:22458512

Preventive effects of conservative treatment with short-term teriparatide on the progression of vertebral body collapse after osteoporotic vertebral compression fracture.

PubMed

Park, J-H; Kang, K-C; Shin, D-E; Koh, Y-G; Son, J-S; Kim, B-H

2014-02-01

The progression of fractured vertebral collapse is not rare after a conservative treatment of vertebral compression fracture (VCF). Teriparatide has been shown to directly stimulate bone formation and improve bone density, but there is a lack of evidence regarding its use in fracture management. Conservative treatment with short-term teriparatide is effective for decreasing the progression of fractured vertebral body collapse. Few studies have reported on the prevention of collapsed vertebral body progression after osteoporotic VCF. Teriparatide rapidly enhances bone formation and increases bone strength. This study evaluated preventive effects of short-term teriparatide on the progression of vertebral body collapse after osteoporotic VCF. Radiographs of 68 women with single-level osteoporotic VCF at thoracolumbar junction (T11-L2) were reviewed. Among them, 32 patients were treated conservatively with teriparatide (minimum 3 months) (group I), and 36 were treated with antiresorptive (group II). We measured kyphosis and wedge angle of the fractured vertebral body, and ratios of anterior, middle, and posterior heights of the collapsed body to posterior height of a normal upper vertebra were determined. The degree of collapse progression was compared between two groups. The progression of fractured vertebral body collapse was shown in both groups, but the degree of progression was significantly lower in group I than in group II. At the last follow-up, mean increments of kyphosis and wedge angle were significantly lower in group I (4.0° ± 4.2° and 3.6° ± 3.6°) than in group II (6.8° ± 4.1° and 5.8° ± 3.5°) (p = 0.032 and p = 0.037). Decrement percentages of anterior and middle border height were significantly lower in group I (9.6 ± 10.3 and 7.4 ± 7.5 %) than in group II (18.1 ± 9.7 and 13.8 ± 12.2 %) (p = 0.001 and p = 0.025), but not in posterior height (p = 0.086). In female patients with single-level osteoporotic VCF at the thoracolumbar junction

Assessment of vertebral microarchitecture in overt and mild Cushing's syndrome using trabecular bone score.

PubMed

Vinolas, Helene; Grouthier, Virginie; Mehsen-Cetre, Nadia; Boisson, Amandine; Winzenrieth, Renaud; Schaeverbeke, Thierry; Mesguich, Charles; Bordenave, Laurence; Tabarin, Antoine

2018-05-21

Osteoporotic fractures associated with Cushing's syndrome (CS) may occur despite normal bone mineral density (BMD). Few studies have described alterations in vertebral microarchitecture in glucocorticoid-treated patients and during CS. Trabecular bone score (TBS) estimates trabecular microarchitecture from dual-energy X-ray absorptiometry acquisitions. Our aim was to compare vertebral BMD and TBS in patients with overt CS and mild autonomous cortisol secretion (MACE), and following cure of overt CS. University Hospital. Monocentric retrospective cross-sectional and longitudinal studies of consecutive patients. A total of 110 patients were studied: 53 patients had CS (35, 11 and 7 patients with Cushing's disease, bilateral macronodular adrenal hyperplasia and ectopic ACTH secretion respectively); 39 patients had MACE (10 patients with a late post-operative recurrence of Cushing's disease and 29 patients with adrenal incidentalomas); 18 patients with non-secreting adrenal incidentalomas. 14 patients with overt CS were followed for up to 2 years after cure. Vertebral osteoporosis at BMD and degraded microarchitecture at TBS were found in 24% and 43% of patients with CS, respectively (P < .03). As compared to patients with nonsecreting incidentalomas, patients with MACE had significantly decreased TBS (P < .04) but not BMD. Overt fragility fractures tended to be associated with low TBS (P = .07) but not with low BMD. TBS, but not BMD values, decreased with the intensity of hypercortisolism independently of its aetiology (P < .01). Following remission of CS, TBS improved more markedly and rapidly than BMD (10% vs 3%, respectively; P < .02). Trabecular bone score may be a promising, noninvasive, widely available and inexpensive complementary tool for the routine assessment of the impact of CS and MACE on bone in clinical practice. © 2018 John Wiley & Sons Ltd.

Evolution of vertebrates: a view from the crest

PubMed Central

Bronner, Marianne E.

2016-01-01

The origin of vertebrates was accompanied by the advent of a novel cell type: the neural crest. Emerging from the central nervous system, these cells migrate to diverse locations and differentiate into numerous derivatives. By coupling morphological and gene regulatory information from vertebrates and other chordates, we describe how addition of the neural crest specification program may have enabled cells at the neural plate border to acquire multipotency and migratory ability. Analyzing the topology of the neural crest gene regulatory network can serve as a useful template for understanding vertebrate evolution, including elaboration of neural crest derivatives. PMID:25903629

Quantitative semi-automated analysis of morphogenesis with single-cell resolution in complex embryos

PubMed Central

Giurumescu, Claudiu A.; Kang, Sukryool; Planchon, Thomas A.; Betzig, Eric; Bloomekatz, Joshua; Yelon, Deborah; Cosman, Pamela; Chisholm, Andrew D.

2012-01-01

A quantitative understanding of tissue morphogenesis requires description of the movements of individual cells in space and over time. In transparent embryos, such as C. elegans, fluorescently labeled nuclei can be imaged in three-dimensional time-lapse (4D) movies and automatically tracked through early cleavage divisions up to ~350 nuclei. A similar analysis of later stages of C. elegans development has been challenging owing to the increased error rates of automated tracking of large numbers of densely packed nuclei. We present Nucleitracker4D, a freely available software solution for tracking nuclei in complex embryos that integrates automated tracking of nuclei in local searches with manual curation. Using these methods, we have been able to track >99% of all nuclei generated in the C. elegans embryo. Our analysis reveals that ventral enclosure of the epidermis is accompanied by complex coordinated migration of the neuronal substrate. We can efficiently track large numbers of migrating nuclei in 4D movies of zebrafish cardiac morphogenesis, suggesting that this approach is generally useful in situations in which the number, packing or dynamics of nuclei present challenges for automated tracking. PMID:23052905

Quantitative semi-automated analysis of morphogenesis with single-cell resolution in complex embryos.

PubMed

Giurumescu, Claudiu A; Kang, Sukryool; Planchon, Thomas A; Betzig, Eric; Bloomekatz, Joshua; Yelon, Deborah; Cosman, Pamela; Chisholm, Andrew D

2012-11-01

A quantitative understanding of tissue morphogenesis requires description of the movements of individual cells in space and over time. In transparent embryos, such as C. elegans, fluorescently labeled nuclei can be imaged in three-dimensional time-lapse (4D) movies and automatically tracked through early cleavage divisions up to ~350 nuclei. A similar analysis of later stages of C. elegans development has been challenging owing to the increased error rates of automated tracking of large numbers of densely packed nuclei. We present Nucleitracker4D, a freely available software solution for tracking nuclei in complex embryos that integrates automated tracking of nuclei in local searches with manual curation. Using these methods, we have been able to track >99% of all nuclei generated in the C. elegans embryo. Our analysis reveals that ventral enclosure of the epidermis is accompanied by complex coordinated migration of the neuronal substrate. We can efficiently track large numbers of migrating nuclei in 4D movies of zebrafish cardiac morphogenesis, suggesting that this approach is generally useful in situations in which the number, packing or dynamics of nuclei present challenges for automated tracking.

The signalling receptor MCAM coordinates apical-basal polarity and planar cell polarity during morphogenesis

PubMed Central

Gao, Qian; Zhang, Junfeng; Wang, Xiumei; Liu, Ying; He, Rongqiao; Liu, Xingfeng; Wang, Fei; Feng, Jing; Yang, Dongling; Wang, Zhaoqing; Meng, Anming; Yan, Xiyun

2017-01-01

The apical–basal (AB) polarity and planar cell polarity (PCP) provide an animal cell population with different phenotypes during morphogenesis. However, how cells couple these two patterning systems remains unclear. Here we provide in vivo evidence that melanoma cell adhesion molecule (MCAM) coordinates AB polarity-driven lumenogenesis and c-Jun N-terminal kinase (JNK)/PCP-dependent ciliogenesis. We identify that MCAM is an independent receptor of fibroblast growth factor 4 (FGF4), a membrane anchor of phospholipase C-γ (PLC-γ), an immediate upstream receptor of nuclear factor of activated T-cells (NFAT) and a constitutive activator of JNK. We find that MCAM-mediated vesicular trafficking towards FGF4, while generating a priority-grade transcriptional response of NFAT determines lumenogenesis. We demonstrate that MCAM plays indispensable roles in ciliogenesis through activating JNK independently of FGF signals. Furthermore, mcam-deficient zebrafish and Xenopus exhibit a global defect in left-right (LR) asymmetric establishment as a result of morphogenetic failure of their LR organizers. Therefore, MCAM coordination of AB polarity and PCP provides insight into the general mechanisms of morphogenesis. PMID:28589943

The Immunoglobulins of Cold-Blooded Vertebrates

PubMed Central

Pettinello, Rita; Dooley, Helen

2014-01-01

Although lymphocyte-like cells secreting somatically-recombining receptors have been identified in the jawless fishes (hagfish and lamprey), the cartilaginous fishes (sharks, skates, rays and chimaera) are the most phylogenetically distant group relative to mammals in which bona fide immunoglobulins (Igs) have been found. Studies of the antibodies and humoral immune responses of cartilaginous fishes and other cold-blooded vertebrates (bony fishes, amphibians and reptiles) are not only revealing information about the emergence and roles of the different Ig heavy and light chain isotypes, but also the evolution of specialised adaptive features such as isotype switching, somatic hypermutation and affinity maturation. It is becoming increasingly apparent that while the adaptive immune response in these vertebrate lineages arose a long time ago, it is most definitely not primitive and has evolved to become complex and sophisticated. This review will summarise what is currently known about the immunoglobulins of cold-blooded vertebrates and highlight the differences, and commonalities, between these and more “conventional” mammalian species. PMID:25427250

Role of mineralization inhibitors in the regulation of hard tissue biomineralization: relevance to initial enamel formation and maturation

PubMed Central

Margolis, Henry C.; Kwak, Seo-Young; Yamazaki, Hajime

2014-01-01

Vertebrate mineralized tissues, i.e., enamel, dentin, cementum, and bone, have unique hierarchical structures and chemical compositions. Although these tissues are similarly comprised of a crystalline calcium apatite mineral phase and a protein component, they differ with respect to crystal size and shape, level and distribution of trace mineral ions, the nature of the proteins present, and their relative proportions of mineral and protein components. Despite apparent differences, mineralized tissues are similarly derived by highly concerted extracellular processes involving matrix proteins, proteases, and mineral ion fluxes that collectively regulate the nucleation, growth and organization of forming mineral crystals. Nature, however, provides multiple ways to control the onset, rate, location, and organization of mineral deposits in developing mineralized tissues. Although our knowledge is quite limited in some of these areas, recent evidence suggests that hard tissue formation is, in part, controlled through the regulation of specific molecules that inhibit the mineralization process. This paper addresses the role of mineralization inhibitors in the regulation of biological mineralization with emphasis on the relevance of current findings to the process of amelogenesis. Mineralization inhibitors can also serve to maintain driving forces for calcium phosphate precipitation and prevent unwanted mineralization. Recent evidence shows that native phosphorylated amelogenins have the capacity to prevent mineralization through the stabilization of an amorphous calcium phosphate precursor phase, as observed in vitro and in developing teeth. Based on present findings, the authors propose that the transformation of initially formed amorphous mineral deposits to enamel crystals is an active process associated with the enzymatic processing of amelogenins. Such processing may serve to control both initial enamel crystal formation and subsequent maturation. PMID:25309443

Vertebral reconstruction using the telescopic plate spacer-thoracolumbar (TPS-TL) device.

PubMed

Atalay, Basar; Riesenburger, Ron I; Schirmer, Clemens M; Bhadelia, Rafeeque A; Weller, Simcha J

2010-07-01

Retrospective study of surgical technique and outcome. The authors conducted a study to evaluate the ability of the TPS-TL (telescopic plate spacer-thoracolumbar) implant to correct kyphotic deformity and restore vertebral body height after vertebrectomy in the thoracolumbar spine. TPS-TL is a novel vertebral body replacement device that consists of an expandable cage with an integrated plate component for transvertebral screw fixation. This is a retrospective study of 20 patients who underwent anterior column reconstruction with TPS-TL after a 1 or 2 level thoracolumbar vertebrectomy. Preoperative and postoperative sagittal alignment and vertebral body heights were radiologically analyzed in all patients. The mean follow-up was 14 months. Preoperative and postoperative Cobb angles were measured to assess sagittal alignment. The average preoperative Cobb angle was 16.0 + or - 7 degrees. This was reduced to 9.8 + or - 10 degrees at the final follow-up (P<0.001). Percent of ideal vertebral body height was used to assess postoperative restoration of vertebral body height. This value was obtained by creating a ratio of the height of the effected vertebral levels to the height of the adjacent normal vertebral bodies. The mean percent of ideal vertebral body height improved from a preoperative value from 86.2 + or - 2% to 93.1 + or - 6% at the final follow-up (P<0.001). The TPS-TL implant is effective in restoring vertebral body height and correcting kyphotic deformity after thoracolumbar vertebrectomy.

Evolution of motor innervation to vertebrate fins and limbs.

PubMed

Murakami, Yasunori; Tanaka, Mikiko

2011-07-01

The evolution and diversification of vertebrate behaviors associated with locomotion depend highly on the functional transformation of paired appendages. Although the evolution of fins into limbs has long been a focus of interest to scientists, the evolution of neural control during this transition has not received much attention. Recent studies have provided significant progress in the understanding of the genetic and developmental bases of the evolution of fin/limb motor circuitry in vertebrates. Here we compare the organization of the motor neurons in the spinal cord of various vertebrates. We also discuss recent advances in our understanding of these events and how they can provide a mechanistic explanation for the evolution of fin/limb motor circuitry in vertebrates. Copyright © 2011 Elsevier Inc. All rights reserved.

The clinical characteristics and therapy of syndrome of craniocerebral-cervical vertebral injury.

PubMed

Liu, Sheng; Liu, Yuan-xin; Wang, Cheng

2005-06-01

To explore the clinical characteristics and new treatment for syndrome of craniocerebral-cervical vertebral injury. The clinical data of 52 patients with head injury accompanied by neck injury were analyzed retrospectively. Craniocerebral injury could result in damage to cervical vertebrae, muscles, vessels and nerves, and even cause vertebral artery injury, which may lead to insufficient blood-supply of vertebral-basal artery. All patients were treated with cervical vertebral traction and the results were good. Acute craniocerebral injury with symptom of insufficient blood-supply of vertebral-basal artery, evident neurosis and atlas-axis half-dislocation in X-ray should be treated by cervical vertebral traction, which will yield better outcome.

Osteoporotic-like effects of cadmium on bone mineral density and content in aged ovariectomized beagles

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

Sacco-Gibson, N.; Abrams, J.; Chaudhry, S.

1992-12-31

Our purpose was to evaluate the effects of ovariectomy in conjunction with cadmium (Cd) exposure on bone. Aged female beagles with {sup 45}Ca-labeled skeletons ovariectomized and exposed to Cd. Successive vertebral scans by dual photon absorptiometry monitored changes in bone mineral density (BMD) in each dog with time. Results showed that ovariectomy or Cd exposure alone caused significant decreases in BMD; ovariectomy with Cd exposure caused the greatest decrease. Ovariectomy alone did not decrease BMD in the distal end or mid-shaft of the tibia while BMD of the distal tibia decreased significantly due to Cd exposure alone. Combination treatment resultedmore » in significant decreases in BMD of both tibial regions. At necropsy, tibiae, humeri, lumbar vertebrae and ribs were obtained for biochemical analysis. No group-to-group differences in bone weights (wet, dry, ash), in ash/dry ratios, or in long bone and vertebral Ca/dry or Ca/ash ratios were observed. Significantly higher total {sup 45}Ca content and {sup 45}Ca/dry and {sup 45}Ca/ash ratios were observed in long bones and vertebrae of OV- and OV+ groups. In contrast, intact ribs showed significantly decreased Ca/dry and Ca/ash ratios compared to the SO-group. Quartered ribs demonstrated regional responses to specific treatment; decreases in total Ca content were greatest in the mid-rib region ({minus}36 to {minus}46%). Results suggest that in the aged female beagle, bone mineral loss associated with estrogen depletion is not only related to bone type (trabecular versus cortical) but also to bone Ca pools. Our results also suggest that a regional heterogeneity of bone plays a role in responsiveness to ovariectomy and Cd exposure. These aspects suggest that Cd is an exogenous factor affecting bone mineral loss independently of estrogen depletion. However, estrogen depletion primes bone for responsiveness to Cd-induced bone mineral loss.« less

Cervical vertebral and dental maturity in Turkish subjects.

PubMed

Başaran, Güvenç; Ozer, Törün; Hamamci, Nihal

2007-04-01

The aim of this study was to investigate the relationships between the stages of calcification of teeth and the cervical vertebral maturity stages in Turkish subjects. A retrospective cross-sectional study was designed. The final study population consisted of 590 Turkish subjects. Statistical analysis of the data was performed with computer software. Spearman rank order correlation coefficients were used to assess the relationship between cervical vertebral and dental maturation. For a better understanding of the relationship between cervical vertebral maturation indexes and dental age, percentage distributions of the studied teeth were also calculated. Strict correlations were found between dental and cervical vertebral maturation of Turkish subjects. For males, the sequence from lowest to the highest was third molar, central incisor, canine, first premolar, second premolar, first molar, and second molar. For females, the sequence from lowest to the highest was third molar, canine, second premolar, first premolar, central incisor, first molar, and second molar. Dental maturation stages can be used as a reliable indicator of facial growth.

Vertebral hemangioma coincident with metastasis of colon adenocarcinoma.

PubMed

Zapałowicz, Krzysztof; Bierzyńska-Macyszyn, Grażyna; Stasiów, Bartłomiej; Krzan, Aleksandra; Wierzycka, Beata; Kopycka, Anna

2016-03-01

The authors report on colon cancer metastasis to the L-3 vertebra, which had been previously found to be involved by an asymptomatic hemangioma. A 61-year-old female patient was admitted after onset of lumbar axial pain and weakness of the right quadriceps muscle. Her medical history included colon cancer that had been diagnosed 3 years earlier and was treated via a right hemicolectomy followed by chemotherapy. Presurgical imaging revealed an asymptomatic hemangioma in the L-3 vertebral body. Computed tomography and MRI of the spine were performed after admission and revealed a hemangioma in the L-3 vertebral body as well as a soft-tissue mass protruding from the L-3 vertebral body to the spinal canal. Treatment consisted of vertebroplasty of the hemangioma, left L-3 hemilaminectomy, and removal of the pathological mass from the spinal canal and the L-3 vertebral body. Histopathological examination revealed the presence of colon cancer metastasis and a hemangioma in the same vertebra.

Allergenicity of vertebrate tropomyosins: Challenging an immunological dogma.

PubMed

González-Fernández, J; Daschner, A; Cuéllar, C

With the exception of tilapia tropomyosin, other anecdotic reports of tropomyosin recognition of vertebrate origin are generally not accompanied by clinical significance and a dogmatic idea is generally accepted about the inexistence of allergenicity of vertebrate tropomyosins, based mainly on sequence similarity evaluations with human tropomyosins. Recently, a specific work-up of a tropomyosin sensitised patient with seafood allergy, demonstrated that the IgE-recognition of tropomyosin from different fish species can be clinically relevant. We hypothesise that some vertebrate tropomyosins could be relevant allergens. The hypothesis is based on the molecular evolution of the proteins and it was tested by in silico methods. Fish, which are primitive vertebrates, could have tropomyosins similar to those of invertebrates. If the hypothesis is confirmed, tropomyosin should be included in different allergy diagnosis tools to improve the medical protocols and management of patients with digestive or cutaneous symptoms after fish intake. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Sea urchin tooth mineralization: calcite present early in the aboral plumula.

PubMed

Stock, Stuart R; Veis, Arthur; Xiao, Xianghui; Almer, Jonathan D; Dorvee, Jason R

2012-11-01

In both vertebrate bone, containing carbonated hydroxyapatite as the mineral phase, and in invertebrate hard tissue comprised of calcium carbonate, a popular view is that the mineral phase develops from a long-lived amorphous precursor which later transforms into crystal form. Important questions linked to this popular view are: when and where is the crystallized material formed, and is amorphous solid added subsequently to the crystalline substrate? Sea urchin teeth, in which the earliest mineral forms within isolated compartments, in a time and position dependent manner, allow direct investigation of the timing of crystallization of the calcite primary plates. Living teeth of the sea urchin Lytechinus variegatus, in their native coelomic fluid, were examined by high-energy synchrotron X-ray diffraction. The diffraction data show that calcite is present in the most aboral portions of the plumula, representing the very earliest stages of mineralization, and that this calcite has the same crystal orientation as in the more mature adoral portions of the same tooth. Raman spectroscopy of the aboral plumula confirms the initial primary plate mineral material is calcite and does not detect amorphous calcium carbonate; in the more mature adoral incisal flange, it does detect a broader calcite peak, consistent with two or more magnesium compositions. We hypothesize that some portion of each syncytial membrane in the plumula provides the information for nucleation of identically oriented calcite crystals that subsequently develop to form the complex geometry of the single crystal sea urchin tooth. Copyright © 2012 Elsevier Inc. All rights reserved.

Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions?

PubMed

Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

2016-03-01

Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. Copyright © 2016 Elsevier Inc. All rights reserved.

The generation of vertebral segmental patterning in the chick embryo.

PubMed

Senthinathan, Biruntha; Sousa, Cátia; Tannahill, David; Keynes, Roger

2012-06-01

We have carried out a series of experimental manipulations in the chick embryo to assess whether the notochord, neural tube and spinal nerves influence segmental patterning of the vertebral column. Using Pax1 expression in the somite-derived sclerotomes as a marker for segmentation of the developing intervertebral disc, our results exclude such an influence. In contrast to certain teleost species, where the notochord has been shown to generate segmentation of the vertebral bodies (chordacentra), these experiments indicate that segmental patterning of the avian vertebral column arises autonomously in the somite mesoderm. We suggest that in amniotes, the subdivision of each sclerotome into non-miscible anterior and posterior halves plays a critical role in establishing vertebral segmentation, and in maintaining left/right alignment of the developing vertebral elements at the body midline. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Evolution of phototransduction, vertebrate photoreceptors and retina.

PubMed

Lamb, Trevor D

2013-09-01

Evidence is reviewed from a wide range of studies relevant to the evolution of vertebrate photoreceptors and phototransduction, in order to permit the synthesis of a scenario for the major steps that occurred during the evolution of cones, rods and the vertebrate retina. The ancestral opsin originated more than 700 Mya (million years ago) and duplicated to form three branches before cnidarians diverged from our own lineage. During chordate evolution, ciliary opsins (C-opsins) underwent multiple stages of improvement, giving rise to the 'bleaching' opsins that characterise cones and rods. Prior to the '2R' rounds of whole genome duplication near the base of the vertebrate lineage, 'cone' photoreceptors already existed; they possessed a transduction cascade essentially the same as in modern cones, along with two classes of opsin: SWS and LWS (short- and long-wave-sensitive). These cones appear to have made synaptic contact directly onto ganglion cells, in a two-layered retina that resembled the pineal organ of extant non-mammalian vertebrates. Interestingly, those ganglion cells appear to be descendants of microvillar photoreceptor cells. No lens was associated with this two-layered retina, and it is likely to have mediated circadian timing rather than spatial vision. Subsequently, retinal bipolar cells evolved, as variants of ciliary photoreceptors, and greatly increased the computational power of the retina. With the advent of a lens and extraocular muscles, spatial imaging information became available for central processing, and gave rise to vision in vertebrates more than 500 Mya. The '2R' genome duplications permitted the refinement of cascade components suitable for both rods and cones, and also led to the emergence of five visual opsins. The exact timing of the emergence of 'true rods' is not yet clear, but it may not have occurred until after the divergence of jawed and jawless vertebrates. Copyright © 2013 The Author. Published by Elsevier Ltd.. All

YAP is essential for tissue tension to ensure vertebrate 3D body shape.

PubMed

Porazinski, Sean; Wang, Huijia; Asaoka, Yoichi; Behrndt, Martin; Miyamoto, Tatsuo; Morita, Hitoshi; Hata, Shoji; Sasaki, Takashi; Krens, S F Gabriel; Osada, Yumi; Asaka, Satoshi; Momoi, Akihiro; Linton, Sarah; Miesfeld, Joel B; Link, Brian A; Senga, Takeshi; Shimizu, Nobuyoshi; Nagase, Hideaki; Matsuura, Shinya; Bagby, Stefan; Kondoh, Hisato; Nishina, Hiroshi; Heisenberg, Carl-Philipp; Furutani-Seiki, Makoto

2015-05-14

Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues.

Collection & Processing of Vertebrate Specimens for Arbovirus Studies.

ERIC Educational Resources Information Center

Sudia, W. Daniel; And Others

Described are techniques used by the National Communicable Disease Center in obtaining blood and tissues from man and other vertebrates for arbovirus isolation and antibody studies. Also included are techniques for capturing and handling vertebrates; banding and marking; restraining and bleeding; storing of specimens to preserve antibody and…

Model of Tooth Morphogenesis Predicts Carabelli Cusp Expression, Size, and Symmetry in Humans

PubMed Central

Hunter, John P.; Guatelli-Steinberg, Debbie; Weston, Theresia C.; Durner, Ryan; Betsinger, Tracy K.

2010-01-01

Background The patterning cascade model of tooth morphogenesis accounts for shape development through the interaction of a small number of genes. In the model, gene expression both directs development and is controlled by the shape of developing teeth. Enamel knots (zones of nonproliferating epithelium) mark the future sites of cusps. In order to form, a new enamel knot must escape the inhibitory fields surrounding other enamel knots before crown components become spatially fixed as morphogenesis ceases. Because cusp location on a fully formed tooth reflects enamel knot placement and tooth size is limited by the cessation of morphogenesis, the model predicts that cusp expression varies with intercusp spacing relative to tooth size. Although previous studies in humans have supported the model's implications, here we directly test the model's predictions for the expression, size, and symmetry of Carabelli cusp, a variation present in many human populations. Methodology/Principal Findings In a dental cast sample of upper first molars (M1s) (187 rights, 189 lefts, and 185 antimeric pairs), we measured tooth area and intercusp distances with a Hirox digital microscope. We assessed Carabelli expression quantitatively as an area in a subsample and qualitatively using two typological schemes in the full sample. As predicted, low relative intercusp distance is associated with Carabelli expression in both right and left samples using either qualitative or quantitative measures. Furthermore, asymmetry in Carabelli area is associated with asymmetry in relative intercusp spacing. Conclusions/Significance These findings support the model's predictions for Carabelli cusp expression both across and within individuals. By comparing right-left pairs of the same individual, our data show that small variations in developmental timing or spacing of enamel knots can influence cusp pattern independently of genotype. Our findings suggest that during evolution new cusps may first appear as

Imperfect Isolation: Factors and Filters Shaping Madagascar’s Extant Vertebrate Fauna

PubMed Central

Samonds, Karen E.; Godfrey, Laurie R.; Ali, Jason R.; Goodman, Steven M.; Vences, Miguel; Sutherland, Michael R.; Irwin, Mitchell T.; Krause, David W.

2013-01-01

Analyses of phylogenetic topology and estimates of divergence timing have facilitated a reconstruction of Madagascar’s colonization events by vertebrate animals, but that information alone does not reveal the major factors shaping the island’s biogeographic history. Here, we examine profiles of Malagasy vertebrate clades through time within the context of the island’s paleogeographical evolution to determine how particular events influenced the arrival of the island’s extant groups. First we compare vertebrate profiles on Madagascar before and after selected events; then we compare tetrapod profiles on Madagascar to contemporary tetrapod compositions globally. We show that changes from the Mesozoic to the Cenozoic in the proportions of Madagascar’s tetrapod clades (particularly its increase in the representation of birds and mammals) are tied to changes in their relative proportions elsewhere on the globe. Differences in the representation of vertebrate classes from the Mesozoic to the Cenozoic reflect the effects of extinction (i.e., the non-random susceptibility of the different vertebrate clades to purported catastrophic global events 65 million years ago), and new evolutionary opportunities for a subset of vertebrates with the relatively high potential for transoceanic dispersal potential. In comparison, changes in vertebrate class representation during the Cenozoic are minor. Despite the fact that the island’s isolation has resulted in high vertebrate endemism and a unique and taxonomically imbalanced extant vertebrate assemblage (both hailed as testimony to its long isolation), that isolation was never complete. Indeed, Madagascar’s extant tetrapod fauna owes more to colonization during the Cenozoic than to earlier arrivals. Madagascar’s unusual vertebrate assemblage needs to be understood with reference to the basal character of clades originating prior to the K-T extinction, as well as to the differential transoceanic dispersal advantage of

Morphogenesis of the human excretory lacrimal system

PubMed Central

de la Cuadra-Blanco, C; Peces-Peña, M D; Jáñez-Escalada, L; Mérida-Velasco, J R

2006-01-01

The aim of this study was to determine the principal developmental stages in the formation of the excretory lacrimal system in humans and to establish its morphogenetic period. The study was performed using light microscopy on serial sections of 51 human specimens: 33 embryos and 18 fetuses ranging from 8 to 137 mm crown–rump length (CR; 5–16 weeks of development). Three stages were identified in the morphogenesis of the excretory lacrimal system: (1) the formative stage of the lacrimal lamina (Carnegie stages 16–18); (2) the formative stage of the lacrimal cord (Carnegie stages 19–23); and (3) the maturative stage of the excretory lacrimal system, from the 9th week of development onward. A three-dimensional reconstruction of the excretory lacrimal system was performed from serial sections of an embryo at the end of the embryonic period (27 mm CR). PMID:16879594

Association between vertebral cross-sectional area and lumbar lordosis angle in adolescents.

PubMed

Wren, Tishya A L; Aggabao, Patricia C; Poorghasamians, Ervin; Chavez, Thomas A; Ponrartana, Skorn; Gilsanz, Vicente

2017-01-01

Lumbar lordosis (LL) is more prominent in women than in men, but the mechanisms responsible for this discrepancy are poorly defined. A recent study indicates that newborn girls have smaller vertebral cross-sectional area (CSA) when compared to boys-a difference that persists throughout life and is independent of body size. We determined the relations between vertebral cross-sectional area (CSA) and LL angle and whether sex differences in lumbar lordosis are related to sex differences in vertebral CSA. Using multi-planar magnetic resonance imaging (MRI), we measured vertebral cross-sectional area (CSA) and vertebral height of the spine of 40 healthy boys and 40 girls, ages 9-13 years. Measures of the CSA of the lumbar vertebrae significantly differed between sexes (9.38 ± 1.46 vs. 7.93 ± 0.69 in boys and girls, respectively; P < 0.0001), while the degree of LL was significantly greater in girls than in boys (23.7 ± 6.1 vs. 27.6 ± 8.0 in boys and girls, respectively; P = 0.02). When all subjects were analyzed together, values for LL angle were negatively correlated to vertebral CSA (r = -0.47; P < 0.0001); this was also true when boys and girls were analyzed separately. Multivariate regression analysis indicated that vertebral CSA was independently associated with LL, even after accounting for sex, age, height or vertebral height, and weight. Similar negative relations were present when thoracic vertebrae were analyzed (Model P < 0.0001, R2 = 0.37, thoracic vertebral CSA slope P < 0.0001), suggesting that deficient vertebral cross-sectional dimensions are not merely the consequence of the anterior lumbar curvature. We conclude that vertebral CSA is negatively associated with LL, and that the greater degree of LL in females could, at least in part, be due to smaller vertebral cross-sectional dimensions. Studies are needed to examine the potential relations between vertebral CSA and spinal conditions known to be associated with increased LL, such as spondylolysis

Association between vertebral cross-sectional area and lumbar lordosis angle in adolescents

PubMed Central

Aggabao, Patricia C.; Poorghasamians, Ervin; Chavez, Thomas A.

2017-01-01

Lumbar lordosis (LL) is more prominent in women than in men, but the mechanisms responsible for this discrepancy are poorly defined. A recent study indicates that newborn girls have smaller vertebral cross-sectional area (CSA) when compared to boys—a difference that persists throughout life and is independent of body size. We determined the relations between vertebral cross-sectional area (CSA) and LL angle and whether sex differences in lumbar lordosis are related to sex differences in vertebral CSA. Using multi-planar magnetic resonance imaging (MRI), we measured vertebral cross-sectional area (CSA) and vertebral height of the spine of 40 healthy boys and 40 girls, ages 9–13 years. Measures of the CSA of the lumbar vertebrae significantly differed between sexes (9.38 ± 1.46 vs. 7.93 ± 0.69 in boys and girls, respectively; P < 0.0001), while the degree of LL was significantly greater in girls than in boys (23.7 ± 6.1 vs. 27.6 ± 8.0 in boys and girls, respectively; P = 0.02). When all subjects were analyzed together, values for LL angle were negatively correlated to vertebral CSA (r = -0.47; P < 0.0001); this was also true when boys and girls were analyzed separately. Multivariate regression analysis indicated that vertebral CSA was independently associated with LL, even after accounting for sex, age, height or vertebral height, and weight. Similar negative relations were present when thoracic vertebrae were analyzed (Model P < 0.0001, R2 = 0.37, thoracic vertebral CSA slope P < 0.0001), suggesting that deficient vertebral cross-sectional dimensions are not merely the consequence of the anterior lumbar curvature. We conclude that vertebral CSA is negatively associated with LL, and that the greater degree of LL in females could, at least in part, be due to smaller vertebral cross-sectional dimensions. Studies are needed to examine the potential relations between vertebral CSA and spinal conditions known to be associated with increased LL, such as

Pleistocene vertebrates of the Yukon Territory

NASA Astrophysics Data System (ADS)

Harington, C. R.

2011-08-01

Unglaciated parts of the Yukon constitute one of the most important areas in North America for yielding Pleistocene vertebrate fossils. Nearly 30 vertebrate faunal localities are reviewed spanning a period of about 1.6 Ma (million years ago) to the close of the Pleistocene some 10 000 BP (radiocarbon years before present, taken as 1950). The vertebrate fossils represent at least 8 species of fishes, 1 amphibian, 41 species of birds and 83 species of mammals. Dominant among the large mammals are: steppe bison ( Bison priscus), horse ( Equus sp.), woolly mammoth ( Mammuthus primigenius), and caribou ( Rangifer tarandus) - signature species of the Mammoth Steppe fauna ( Fig. 1), which was widespread from the British Isles, through northern Europe, and Siberia to Alaska, Yukon and adjacent Northwest Territories. The Yukon faunas extend from Herschel Island in the north to Revenue Creek in the south and from the Alaskan border in the west to Ketza River in the east. The Yukon holds evidence of the earliest-known people in North America. Artifacts made from bison, mammoth and caribou bones from Bluefish Caves, Old Crow Basin and Dawson City areas show that people had a substantial knowledge of making and using bone tools at least by 25 000 BP, and possibly as early as 40 000 BP. A suggested chronological sequence of Yukon Pleistocene vertebrates ( Table 1) facilitates comparison of selected faunas and indicates the known duration of various taxa.

Distinct subsets of Eve-positive pericardial cells stabilise cardiac outflow and contribute to Hox gene-triggered heart morphogenesis in Drosophila.

PubMed

Zmojdzian, Monika; de Joussineau, Svetlana; Da Ponte, Jean Philippe; Jagla, Krzysztof

2018-01-17

The Drosophila heart, composed of discrete subsets of cardioblasts and pericardial cells, undergoes Hox-triggered anterior-posterior morphogenesis, leading to a functional subdivision into heart proper and aorta, with its most anterior part forming a funnel-shaped cardiac outflow. Cardioblasts differentiate into Tin-positive 'working myocytes' and Svp-expressing ostial cells. However, developmental fates and functions of heart-associated pericardial cells remain elusive. Here, we show that the pericardial cells that express the transcription factor Even Skipped adopt distinct fates along the anterior-posterior axis. Among them, the most anterior Antp-Ubx-AbdA - negative cells form a novel cardiac outflow component we call the outflow hanging structure, whereas the Antp-expressing cells differentiate into wing heart precursors. Interestingly, Hox gene expression in the Even Skipped-positive cells not only underlies their antero-posterior diversification, but also influences heart morphogenesis in a non-cell-autonomous way. In brief, we identify a new cardiac outflow component derived from a subset of Even Skipped-expressing cells that stabilises the anterior heart tip, and demonstrate non-cell-autonomous effects of Hox gene expression in the Even Skipped-positive cells on heart morphogenesis. © 2018. Published by The Company of Biologists Ltd.

Comparison of Radiofrequency-targeted Vertebral Augmentation With Balloon Kyphoplasty for the Treatment of Vertebral Compression Fractures: 2-Year Results.

PubMed

Bornemann, Rahel; Jansen, Tom R; Kabir, Koroush; Pennekamp, Peter H; Stüwe, Brit; Wirtz, Dieter C; Pflugmacher, Robert

2017-04-01

A retrospective study. The aim of this study was the evaluation of the safety and effectiveness of radiofrequency-targeted vertebral augmentation (RF-TVA) in comparison with balloon kyphoplasty (BK) for the treatment of acute painful vertebral compression fractures (VCFs) on the basis of matched pairs. Vertebroplasty and BK are the common surgical interventions for the treatment of VCF. Both are effective and safe but pose some risks such as adjacent fractures and cement leakage. In 2009, RF-TVA was introduced as an innovative augmentation procedure for the treatment of VCF. A total of 192 patients (116 female; 51-90 y) with VCF (n=303) at 1 to 3 levels were treated with RF-TVA or BK. Functionality (Oswestry Disability Index), pain (visual analogue scale), vertebral height (anterior, middle), and kyphotic angle were evaluated over a 2-year period (postoperatively, 3-4 d, 3, 6, 12, and 24 mo). In addition, operating time and occurrence of cement leakage were recorded. Pain and functionality were significantly improved after both treatments. In both groups, there was an increase in the vertebral height and a decrease in the kyphotic angle, which remained relatively consistent during 24 months. The incidence of cement leakage was 9.4% (n=9) in the RF-TVA group and 24.0% (n=25) in the BK group. The mean operating time with radiofrequency kyphoplasty was 25.9±9.9 minutes, and with balloon kyphoplasty 48.0±18.4 minutes. RF-TVA is a safe and effective procedure for the treatment of vertebral compression fractures when compared with BK. Improvement in pain and functional scores after RF-TVA are durable through 24 months postprocedure and remained better than those after BK at long-term follow-up. Operating time for RF-TVA is shorter and the risk of cement leakage is lower. Both procedures provided similar results in vertebral height restoration and reduction in the kyphotic angle.

A new heart for a new head in vertebrate cardiopharyngeal evolution.

PubMed

Diogo, Rui; Kelly, Robert G; Christiaen, Lionel; Levine, Michael; Ziermann, Janine M; Molnar, Julia L; Noden, Drew M; Tzahor, Eldad

2015-04-23

It has been more than 30 years since the publication of the new head hypothesis, which proposed that the vertebrate head is an evolutionary novelty resulting from the emergence of neural crest and cranial placodes. Neural crest generates the skull and associated connective tissues, whereas placodes produce sensory organs. However, neither crest nor placodes produce head muscles, which are a crucial component of the complex vertebrate head. We discuss emerging evidence for a surprising link between the evolution of head muscles and chambered hearts - both systems arise from a common pool of mesoderm progenitor cells within the cardiopharyngeal field of vertebrate embryos. We consider the origin of this field in non-vertebrate chordates and its evolution in vertebrates.

Management of vertebral compression fracture in general practice: BEACH program.

PubMed

Megale, Rodrigo Z; Pollack, Allan; Britt, Helena; Latimer, Jane; Naganathan, Vasi; McLachlan, Andrew J; Ferreira, Manuela L

2017-01-01

The pain associated with vertebral compression fractures can cause significant loss of function and quality of life for older adults. Despite this, there is little consensus on how best to manage this condition. To describe usual care provided by general practitioners (GPs) in Australia for the management of vertebral compression fractures. Data from the Bettering the Evaluation And Care of Health (BEACH) program collected between April 2005 and March 2015 was used for this study. Each year, a random sample of approximately 1,000 GPs each recorded information on 100 consecutive encounters. We selected those encounters at which vertebral compression fracture was managed. Analyses of management options were limited to encounters with patients aged 50 years or over. i) patient demographics; ii) diagnoses/problems managed; iii) the management provided for vertebral compression fracture during the encounter. Robust 95% confidence intervals, adjusted for the cluster survey design, were used to assess significant differences between group means. Vertebral compression fractures were managed in 211 (0.022%; 95% CI: 0.018-0.025) of the 977,300 BEACH encounters recorded April 2005- March 2015. That provides a national annual estimate of 26,000 (95% CI: 22,000-29,000) encounters at which vertebral fractures were managed. At encounters with patients aged 50 years or over (those at higher risk of primary osteoporosis), prescription of analgesics was the most common management action, particularly opioids analgesics (47.1 per 100 vertebral fractures; 95% CI: 38.4-55.7). Prescriptions of paracetamol (8.2; 95% CI: 4-12.4) or non-steroidal anti-inflammatory drugs (4.1; 95% CI: 1.1-7.1) were less frequent. Non-pharmacological treatment was provided at a rate of 22.4 per 100 vertebral fractures (95% CI: 14.6-30.1). At least one referral (to hospital, specialist, allied health care or other) was given for 12.3 per 100 vertebral fractures (95% CI: 7.8-16.8). The prescription of oral

Evolution and the origin of the visual retinoid cycle in vertebrates.

PubMed

Kusakabe, Takehiro G; Takimoto, Noriko; Jin, Minghao; Tsuda, Motoyuki

2009-10-12

Absorption of a photon by visual pigments induces isomerization of 11-cis-retinaldehyde (RAL) chromophore to all-trans-RAL. Since the opsins lacking 11-cis-RAL lose light sensitivity, sustained vision requires continuous regeneration of 11-cis-RAL via the process called 'visual cycle'. Protostomes and vertebrates use essentially different machinery of visual pigment regeneration, and the origin and early evolution of the vertebrate visual cycle is an unsolved mystery. Here we compare visual retinoid cycles between different photoreceptors of vertebrates, including rods, cones and non-visual photoreceptors, as well as between vertebrates and invertebrates. The visual cycle systems in ascidians, the closest living relatives of vertebrates, show an intermediate state between vertebrates and non-chordate invertebrates. The ascidian larva may use retinochrome-like opsin as the major isomerase. The entire process of the visual cycle can occur inside the photoreceptor cells with distinct subcellular compartmentalization, although the visual cycle components are also present in surrounding non-photoreceptor cells. The adult ascidian probably uses RPE65 isomerase, and trans-to-cis isomerization may occur in distinct cellular compartments, which is similar to the vertebrate situation. The complete transition to the sophisticated retinoid cycle of vertebrates may have required acquisition of new genes, such as interphotoreceptor retinoid-binding protein, and functional evolution of the visual cycle genes.