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Sample records for notochord morphogenesis vertebral

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Axial Protocadherin (AXPC) regulates cell fate during notochordal morphogenesis

    PubMed Central

    Yoder, Michael D.; Gumbiner, Barry M.

    2011-01-01

    The separation and specification of mesoderm into the notochord and somites involves members of the non-clustered δ-protocadherins. Axial (AXPC) and paraxial (PAPC) protocadherins are expressed in the early dorsal mesoderm and later become refined to the developing notochordal and somitic mesoderm respectively. The role of PAPC in this process has been studied extensively, but the role of AXPC is poorly understood. Partial knockdown of AXPC causes a specific bent axis phenotype, while more severe knockdown results in the loss of notochord formation. The inability of these embryos to develop a notochord is not due to a cell-sorting event via changes in cell adhesion during gastrulation, but rather this defect is manifested through the loss of axial mesoderm specification, but not general mesoderm induction. The results presented here show that AXPC functions in notochord morphogenesis by directing cell fate decisions rather than cell-cell adhesion. PMID:21960065

  6. 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.

  7. The mouse homeobox gene Noto regulates node morphogenesis, notochordal ciliogenesis, and left right patterning.

    PubMed

    Beckers, Anja; Alten, Leonie; Viebahn, Christoph; Andre, Philipp; Gossler, Achim

    2007-10-02

    The mouse homeobox gene Noto represents the homologue of zebrafish floating head (flh) and is expressed in the organizer node and in the nascent notochord. Previous analyses suggested that Noto is required exclusively for the formation of the caudal part of the notochord. Here, we show that Noto is also essential for node morphogenesis, controlling ciliogenesis in the posterior notochord, and the establishment of laterality, whereas organizer functions in anterior-posterior patterning are apparently not compromised. In mutant embryos, left-right asymmetry of internal organs and expression of laterality markers was randomized. Mutant posterior notochord regions were variable in size and shape, cilia were shortened with highly irregular axonemal microtubuli, and basal bodies were, in part, located abnormally deep in the cytoplasm. The transcription factor Foxj1, which regulates the dynein gene Dnahc11 and is required for the correct anchoring of basal bodies in lung epithelial cells, was down-regulated in mutant nodes. Likewise, the transcription factor Rfx3, which regulates cilia growth, was not expressed in Noto mutants, and various other genes important for cilia function or assembly such as Dnahc5 and Nphp3 were down-regulated. Our results establish Noto as an essential regulator of node morphogenesis and ciliogenesis in the posterior notochord, and suggest Noto acts upstream of Foxj1 and Rfx3.

  8. Distinct patterns of notochord mineralization in zebrafish coincide with the localization of Osteocalcin isoform 1 during early vertebral centra formation

    PubMed Central

    2012-01-01

    Background In chondrichthyans, basal osteichthyans and tetrapods, vertebral bodies have cartilaginous anlagen that subsequently mineralize (chondrichthyans) or ossify (osteichthyans). Chondrocytes that form the vertebral centra derive from somites. In teleost fish, vertebral centrum formation starts in the absence of cartilage, through direct mineralization of the notochord sheath. In a second step, the notochord is surrounded by somite-derived intramembranous bone. In several small teleost species, including zebrafish (Danio rerio), even haemal and neural arches form directly as intramembranous bone and only modified caudalmost arches remain cartilaginous. This study compares initial patterns of mineralization in different regions of the vertebral column in zebrafish. We ask if the absence or presence of cartilaginous arches influences the pattern of notochord sheath mineralization. Results To reveal which cells are involved in mineralization of the notochord sheath we identify proliferating cells, we trace mineralization on the histological level and we analyze cell ultrastructure by TEM. Moreover, we localize proteins and genes that are typically expressed by skeletogenic cells such as Collagen type II, Alkaline phosphatase (ALP) and Osteocalcin (Oc). Mineralization of abdominal and caudal vertebrae starts with a complete ring within the notochord sheath and prior to the formation of the bony arches. In contrast, notochord mineralization of caudal fin centra starts with a broad ventral mineral deposition, associated with the bases of the modified cartilaginous arches. Similar, arch-related, patterns of mineralization occur in teleosts that maintain cartilaginous arches throughout the spine. Throughout the entire vertebral column, we were able to co-localize ALP-positive signal with chordacentrum mineralization sites, as well as Collagen II and Oc protein accumulation in the mineralizing notochord sheath. In the caudal fin region, ALP and Oc signals were clearly

  9. Planar Cell Polarity in vertebrate limb morphogenesis

    PubMed Central

    Gao, Bo; Yang, Yingzi

    2013-01-01

    Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/Planar Cell Polarity (PCP) pathway that controls uniformly polarized cellular behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner. PMID:23747034

  10. Planar cell polarity in vertebrate limb morphogenesis.

    PubMed

    Gao, Bo; Yang, Yingzi

    2013-08-01

    Studies of the vertebrate limb development have contributed significantly to understanding the fundamental mechanisms underlying growth, patterning, and morphogenesis of a complex multicellular organism. In the limb, well-defined signaling centers interact to coordinate limb growth and patterning along the three axes. Recent analyses of live imaging and mathematical modeling have provided evidence that polarized cell behaviors governed by morphogen gradients play an important role in shaping the limb bud. Furthermore, the Wnt/planar cell polarity (PCP) pathway that controls uniformly polarized cell behaviors in a field of cells has emerged to be critical for directional morphogenesis in the developing limb. Directional information coded in the morphogen gradient may be interpreted by responding cells through regulating the activities of PCP components in a Wnt morphogen dose-dependent manner.

  11. Microtubules, polarity and vertebrate neural tube morphogenesis.

    PubMed

    Cearns, Michael D; Escuin, Sarah; Alexandre, Paula; Greene, Nicholas D E; Copp, Andrew J

    2016-07-01

    Microtubules (MTs) are key cellular components, long known to participate in morphogenetic events that shape the developing embryo. However, the links between the cellular functions of MTs, their effects on cell shape and polarity, and their role in large-scale morphogenesis remain poorly understood. Here, these relationships were examined with respect to two strategies for generating the vertebrate neural tube: bending and closure of the mammalian neural plate; and cavitation of the teleost neural rod. The latter process has been compared with 'secondary' neurulation that generates the caudal spinal cord in mammals. MTs align along the apico-basal axis of the mammalian neuroepithelium early in neural tube closure, participating functionally in interkinetic nuclear migration, which indirectly impacts on cell shape. Whether MTs play other functional roles in mammalian neurulation remains unclear. In the zebrafish, MTs are important for defining the neural rod midline prior to its cavitation, both by localizing apical proteins at the tissue midline and by orienting cell division through a mirror-symmetric MT apparatus that helps to further define the medial localization of apical polarity proteins. Par proteins have been implicated in centrosome positioning in neuroepithelia as well as in the control of polarized morphogenetic movements in the neural rod. Understanding of MT functions during early nervous system development has so far been limited, partly by techniques that fail to distinguish 'cause' from 'effect'. Future developments will likely rely on novel ways to selectively impair MT function in order to investigate the roles they play.

  12. Microtubules, polarity and vertebrate neural tube morphogenesis

    PubMed Central

    Cearns, Michael D.; Escuin, Sarah; Alexandre, Paula; Greene, Nicholas D. E.; Copp, Andrew J.

    2016-01-01

    Microtubules are key cellular components, long known to participate in morphogenetic events that shape the developing embryo. However, the links between the cellular functions of microtubules, their effects on cell shape and polarity and their role in large-scale morphogenesis remain poorly understood. Here, we examine these relationships with respect to two strategies for generating the vertebrate neural tube: bending and closure of the mammalian neural plate, and cavitation of the teleost neural rod. The latter process has been compared to ‘secondary’ neurulation that generates the caudal spinal cord in mammals. Microtubules align along the apico-basal axis of the mammalian neuroepithelium early in neural tube closure, participating functionally in interkinetic nuclear migration which indirectly impacts on cell shape. Whether microtubules play other functional roles in mammalian neurulation remains unclear. In the zebrafish, microtubules are important for defining the neural rod midline prior to its cavitation, both by localizing apical proteins at the tissue midline and by orienting cell division through a mirror-symmetric microtubule apparatus that helps to further define the medial localization of apical polarity proteins. Par proteins have been implicated in centrosome positioning in neuroepithelia as well as in the control of polarized morphogenetic movements in the neural rod. Understanding of microtubule functions during early nervous system development has so far been limited, partly by techniques that fail to distinguish ‘cause’ from ‘effect’. Future developments will likely rely on novel ways to selectively impair microtubule function in order to investigate the roles they play. PMID:27025884

  13. 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

  14. 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

  15. Benign notochordal cell tumors.

    PubMed

    Martínez Gamarra, C; Bernabéu Taboada, D; Pozo Kreilinger, J J; Tapia Viñé, M

    2017-08-01

    Benign notochordal cell tumors (TBCN) are lesions with notochordal differentiation which affect the axial skeleton. They are characterized by asymptomatic or non-specific symptomatology and are radiologically unnoticed because of their small size, or because they are mistaken with other benign bone lesions, such as vertebral hemangiomas. When they are large, or symptomatic, can be differential diagnosis with metastases, primary bone tumors and chordomas. We present a case of a TBCN in a 50-year-old woman, with a sacral lesion seen in MRI. A CT-guided biopsy was scheduled to analyze the lesion, finding that the tumor was not clearly recognizable on CT, so the anatomical references of MRI were used to select the appropriate plane. The planning of the approach and the radio-pathological correlation were determinant to reach the definitive diagnosis. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Stochasticity and stereotypy in the Ciona notochord.

    PubMed

    Carlson, Maia; Reeves, Wendy; Veeman, Michael

    2015-01-15

    Fate mapping with single cell resolution has typically been confined to embryos with completely stereotyped development. The lineages giving rise to the 40 cells of the Ciona notochord are invariant, but the intercalation of those cells into a single-file column is not. Here we use genetic labeling methods to fate map the Ciona notochord with both high resolution and large sample sizes. We find that the ordering of notochord cells into a single column is not random, but instead shows a distinctive signature characteristic of mediolaterally-biased intercalation. We find that patterns of cell intercalation in the notochord are somewhat stochastic but far more stereotyped than previously believed. Cell behaviors vary by lineage, with the secondary notochord lineage being much more constrained than the primary lineage. Within the primary lineage, patterns of intercalation reflect the geometry of the intercalating tissue. We identify the latest point at which notochord morphogenesis is largely stereotyped, which is shortly before the onset of mediolateral intercalation and immediately after the final cell divisions in the primary lineage. These divisions are consistently oriented along the AP axis. Our results indicate that the interplay between stereotyped and stochastic cell behaviors in morphogenesis can only be assessed by fate mapping experiments that have both cellular resolution and large sample sizes. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Coming into focus: the role of extracellular matrix in vertebrate optic cup morphogenesis.

    PubMed

    Kwan, Kristen M

    2014-10-01

    The vertebrate eye acquires its basic form during the process of optic cup morphogenesis, during which the optic vesicle emerges from the brain neuroepithelium and, through a series of cell and tissue movements, transforms itself into the multilayered optic cup, containing neural retina (comprised of retinal progenitors), retinal pigmented epithelium, and the lens, which is derived from the overlying ectoderm. While great strides have been made to understand the developmental signals controlling specification, patterning, and differentiation of the optic cup, only in recent years have the cellular and molecular bases of optic cup morphogenesis begun to be unraveled. One critical component of the morphogenetic process is the extracellular matrix: the complex, glycoprotein-rich layer that surrounds the optic vesicle and lens. Though the extracellular matrix has long been visualized by classical histological techniques and postulated to play various roles in optic cup development, its functional role was uncertain. This is now beginning to change, as live imaging techniques, quantitative image analyses, molecular genetics and in vitro models yield new insights into the process of optic cup morphogenesis and the specific influences of particular extracellular matrix components and their associated signaling pathways.

  18. HNK-1 immunoreactivity during early morphogenesis of the head region in a nonmodel vertebrate, crocodile embryo.

    PubMed

    Kundrát, Martin

    2008-11-01

    The present study examines HNK-1 immunoidentification of a population of the neural crest (NC) during early head morphogenesis in the nonmodel vertebrate, the crocodile (Crocodylus niloticus) embryos. Although HNK-1 is not an exclusive NC marker among vertebrates, temporospatial immunoreactive patterns found in the crocodile are almost consistent with NC patterns derived from gene expression studies known in birds (the closest living relatives of crocodiles) and mammals. In contrast to birds, the HNK-1 epitope is immunoreactive in NC cells at the neural fold level in crocodile embryos and therefore provides sufficient base to assess early migratory events of the cephalic NC. I found that crocodile NC forms three classic migratory pathways in the head: mandibular, hyoid, and branchial. Further, I demonstrate that, besides this classic phenotype, there is also a forebrain-derived migratory population, which consolidates into a premandibular stream in the crocodile. In contrast to the closely related chick model, crocodilian premandibular and mandibular NC cells arise from the open neural tube suggesting that species-specific heterochronic behavior of NC may be involved in the formation of different vertebrate facial phenotypes.

  19. HNK-1 immunoreactivity during early morphogenesis of the head region in a nonmodel vertebrate, crocodile embryo

    NASA Astrophysics Data System (ADS)

    Kundrát, Martin

    2008-11-01

    The present study examines HNK-1 immunoidentification of a population of the neural crest (NC) during early head morphogenesis in the nonmodel vertebrate, the crocodile ( Crocodylus niloticus) embryos. Although HNK-1 is not an exclusive NC marker among vertebrates, temporospatial immunoreactive patterns found in the crocodile are almost consistent with NC patterns derived from gene expression studies known in birds (the closest living relatives of crocodiles) and mammals. In contrast to birds, the HNK-1 epitope is immunoreactive in NC cells at the neural fold level in crocodile embryos and therefore provides sufficient base to assess early migratory events of the cephalic NC. I found that crocodile NC forms three classic migratory pathways in the head: mandibular, hyoid, and branchial. Further, I demonstrate that, besides this classic phenotype, there is also a forebrain-derived migratory population, which consolidates into a premandibular stream in the crocodile. In contrast to the closely related chick model, crocodilian premandibular and mandibular NC cells arise from the open neural tube suggesting that species-specific heterochronic behavior of NC may be involved in the formation of different vertebrate facial phenotypes.

  20. Dynamic Coupling of Pattern Formation and Morphogenesis in the Developing Vertebrate Retina

    PubMed Central

    Picker, Alexander; Cavodeassi, Florencia; Machate, Anja; Bernauer, Sabine; Hans, Stefan; Abe, Gembu; Kawakami, Koichi; Wilson, Stephen W.; Brand, Michael

    2009-01-01

    During embryonic development, pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements. In the vertebrate retina, patterning along the dorsal-ventral and nasal-temporal (anterior-posterior) axes is required for correct spatial representation in the retinotectal map. However, it is unknown how specification of axial cell positions in the retina occurs during the complex process of early eye morphogenesis. Studying zebrafish embryos, we show that morphogenetic tissue rearrangements during eye evagination result in progenitor cells in the nasal half of the retina primordium being brought into proximity to the sources of three fibroblast growth factors, Fgf8/3/24, outside the eye. Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. Surprisingly, nasal-temporal axis specification occurs very early along the dorsal-ventral axis of the evaginating eye. By in vivo imaging GFP-tagged retinal progenitor cells, we find that subsequent eye morphogenesis requires gradual tissue compaction in the nasal half and directed cell movements into the temporal half of the retina. Balancing these processes drives the progressive alignment of the nasal-temporal retina axis with the anterior-posterior body axis and is controlled by a feed-forward effect of Fgf signaling on Foxg1-mediated cell cohesion. Thus, the mechanistic coupling and dynamic synchronization of tissue patterning with morphogenetic cell behavior through Fgf signaling leads to the graded allocation of cell positional identity in the eye, underlying retinotectal map formation. PMID:19823566

  1. Dynamic coupling of pattern formation and morphogenesis in the developing vertebrate retina.

    PubMed

    Picker, Alexander; Cavodeassi, Florencia; Machate, Anja; Bernauer, Sabine; Hans, Stefan; Abe, Gembu; Kawakami, Koichi; Wilson, Stephen W; Brand, Michael

    2009-10-01

    During embryonic development, pattern formation must be tightly synchronized with tissue morphogenesis to coordinate the establishment of the spatial identities of cells with their movements. In the vertebrate retina, patterning along the dorsal-ventral and nasal-temporal (anterior-posterior) axes is required for correct spatial representation in the retinotectal map. However, it is unknown how specification of axial cell positions in the retina occurs during the complex process of early eye morphogenesis. Studying zebrafish embryos, we show that morphogenetic tissue rearrangements during eye evagination result in progenitor cells in the nasal half of the retina primordium being brought into proximity to the sources of three fibroblast growth factors, Fgf8/3/24, outside the eye. Triple-mutant analysis shows that this combined Fgf signal fully controls nasal retina identity by regulating the nasal transcription factor Foxg1. Surprisingly, nasal-temporal axis specification occurs very early along the dorsal-ventral axis of the evaginating eye. By in vivo imaging GFP-tagged retinal progenitor cells, we find that subsequent eye morphogenesis requires gradual tissue compaction in the nasal half and directed cell movements into the temporal half of the retina. Balancing these processes drives the progressive alignment of the nasal-temporal retina axis with the anterior-posterior body axis and is controlled by a feed-forward effect of Fgf signaling on Foxg1-mediated cell cohesion. Thus, the mechanistic coupling and dynamic synchronization of tissue patterning with morphogenetic cell behavior through Fgf signaling leads to the graded allocation of cell positional identity in the eye, underlying retinotectal map formation.

  2. Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation.

    PubMed

    Sullivan-Brown, Jessica L; Tandon, Panna; Bird, Kim E; Dickinson, Daniel J; Tintori, Sophia C; Heppert, Jennifer K; Meserve, Joy H; Trogden, Kathryn P; Orlowski, Sara K; Conlon, Frank L; Goldstein, Bob

    2016-01-01

    Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells' apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems.

  3. Identifying Regulators of Morphogenesis Common to Vertebrate Neural Tube Closure and Caenorhabditis elegans Gastrulation

    PubMed Central

    Sullivan-Brown, Jessica L.; Tandon, Panna; Bird, Kim E.; Dickinson, Daniel J.; Tintori, Sophia C.; Heppert, Jennifer K.; Meserve, Joy H.; Trogden, Kathryn P.; Orlowski, Sara K.; Conlon, Frank L.; Goldstein, Bob

    2016-01-01

    Neural tube defects including spina bifida are common and severe congenital disorders. In mice, mutations in more than 200 genes can result in neural tube defects. We hypothesized that this large gene set might include genes whose homologs contribute to morphogenesis in diverse animals. To test this hypothesis, we screened a set of Caenorhabditis elegans homologs for roles in gastrulation, a topologically similar process to vertebrate neural tube closure. Both C. elegans gastrulation and vertebrate neural tube closure involve the internalization of surface cells, requiring tissue-specific gene regulation, actomyosin-driven apical constriction, and establishment and maintenance of adhesions between specific cells. Our screen identified several neural tube defect gene homologs that are required for gastrulation in C. elegans, including the transcription factor sptf-3. Disruption of sptf-3 in C. elegans reduced the expression of early endodermally expressed genes as well as genes expressed in other early cell lineages, establishing sptf-3 as a key contributor to multiple well-studied C. elegans cell fate specification pathways. We also identified members of the actin regulatory WAVE complex (wve-1, gex-2, gex-3, abi-1, and nuo-3a). Disruption of WAVE complex members reduced the narrowing of endodermal cells’ apical surfaces. Although WAVE complex members are expressed broadly in C. elegans, we found that expression of a vertebrate WAVE complex member, nckap1, is enriched in the developing neural tube of Xenopus. We show that nckap1 contributes to neural tube closure in Xenopus. This work identifies in vivo roles for homologs of mammalian neural tube defect genes in two manipulable genetic model systems. PMID:26434722

  4. Development of the annelid axochord: insights into notochord evolution.

    PubMed

    Lauri, Antonella; Brunet, Thibaut; Handberg-Thorsager, Mette; Fischer, Antje H L; Simakov, Oleg; Steinmetz, Patrick R H; Tomer, Raju; Keller, Philipp J; Arendt, Detlev

    2014-09-12

    The origin of chordates has been debated for more than a century, with one key issue being the emergence of the notochord. In vertebrates, the notochord develops by convergence and extension of the chordamesoderm, a population of midline cells of unique molecular identity. We identify a population of mesodermal cells in a developing invertebrate, the marine annelid Platynereis dumerilii, that converges and extends toward the midline and expresses a notochord-specific combination of genes. These cells differentiate into a longitudinal muscle, the axochord, that is positioned between central nervous system and axial blood vessel and secretes a strong collagenous extracellular matrix. Ancestral state reconstruction suggests that contractile mesodermal midline cells existed in bilaterian ancestors. We propose that these cells, via vacuolization and stiffening, gave rise to the chordate notochord. Copyright © 2014, American Association for the Advancement of Science.

  5. Immunohistochemical Studies of Cytoskeletal and Extracellular Matrix Components in Dogfish Scyliorhinus canicula L. Notochordal Cells.

    PubMed

    Restović, Ivana; Vukojević, Katarina; Paladin, Antonela; Saraga-Babić, Mirna; Bočina, Ivana

    2015-10-01

    Immunofluorescence and immunohistochemical techniques were used to define the distribution of cytoskeletal (cytokeratin 8, vimentin) and extracellular matrix components (collagen type I, collagen type II, hyaluronic acid, and aggrecan) and bone morphogenetic proteins 4 and 7 (BMP4 and BMP7) in the notochord of the lesser spotted dogfish Scyliorhinus canicula L. Immunolocalization of hyaluronic acid was observed in the notochord, vertebral centrum, and neural and hemal arches, while positive labeling to aggrecan was observed in the ossified centrum, notochord, and the perichondrium of the hyaline cartilage. Type I collagen was observed in the mineralized cartilage of the vertebral bodies, the notochord, the fibrocartilage of intervertebral disc, and the perichondrium. A positive labeling to type II collagen was observed in the inner part of the cartilaginous vertebral centrum and the notochord, as well as in the neural arch and muscle tissue, but there was no appreciable labeling of the hyaline cartilage. The presence of both BMP4 and BMP7 was seen in the mineralized vertebral centrum, notochordal cells, and neural arch. The notochordal cells expressed both cytokeratin 8 and vimentin, but predominantly vimentin. Hyaluronic acid, collagen type I, and collagen type II expression confirmed the presence of a mixture of notochordal and fibrocartilaginous tissue in the intervertebral disc, while BMPs confirmed the presence of an ossification in the cartilaginous skeleton of the spotted dogfish. © 2015 Wiley Periodicals, Inc.

  6. Update on the Notochord Including its Embryology, Molecular Development, and Pathology: A Primer for the Clinician

    PubMed Central

    Ramesh, Tushar; Nagula, Sai V; Saker, Erfanul; Shoja, Mohammadali; Loukas, Marios; Oskouian, Rod J; Tubbs, R. Shane

    2017-01-01

    The notochord is a rod-like embryological structure, which plays a vital role in the development of the vertebrate. Though embryological, remnants of this structure have been observed in the nucleus pulposus of the intervertebral discs of normal adults. Pathologically, these remnants can give rise to slow-growing and recurrent notochord-derived tumors called chordomas. Using standard search engines, the literature was reviewed regarding the anatomy, embryology, molecular development, and pathology of the human notochord. Clinicians who interpret imaging or treat patients with pathologies linked to the notochord should have a good working knowledge of its development and pathology. PMID:28480155

  7. Split notochord syndrome with congenital unilateral Horner's sign.

    PubMed

    Kumakura, Akira; Takahara, Tadamori; Asada, Junko; Matsukawa, Yasuhiro; Hata, Daisuke

    2008-01-01

    A 2-year-old boy exhibited congenital right Horner's sign and right finger, wrist, and elbow flexion arthrogryposis. He had dyspnea and feeding difficulty 12 hours after birth. Radiologic examination revealed a thoracoabdominal intestinal tube and mediastinal cystic lesion at the right side, with vertebral anomaly at the cervical level. Histopathologically, the intestinal tube was diagnosed as bowel duplication. Because the mediastinal lesion could not be resected surgically, no histopathological diagnosis was made. Embryologically, the combination of transdiaphragmatic duplication, mediastinal cystic lesion, anterior spina bifida, and hemivertebra suggested notochord malformation. The diagnosis was split notochord syndrome, an extremely rare embryological malformation syndrome. Congenital unilateral Horner syndrome often has unknown etiology. In this case, cervical vertebral anomalies and mediastinal cystic lesion implied a compressed nerve root, resulting in Horner syndrome and right finger, wrist, and elbow flexion joint contracture. Split notochord syndrome should be included in differential diagnosis of congenital unilateral Horner syndrome.

  8. Loss of laminin alpha 1 results in multiple structural defects and divergent effects on adhesion during vertebrate optic cup morphogenesis.

    PubMed

    Bryan, Chase D; Chien, Chi-Bin; Kwan, Kristen M

    2016-08-15

    The vertebrate eye forms via a complex set of morphogenetic events. The optic vesicle evaginates and undergoes transformative shape changes to form the optic cup, in which neural retina and retinal pigmented epithelium enwrap the lens. It has long been known that a complex, glycoprotein-rich extracellular matrix layer surrounds the developing optic cup throughout the process, yet the functions of the matrix and its specific molecular components have remained unclear. Previous work established a role for laminin extracellular matrix in particular steps of eye development, including optic vesicle evagination, lens differentiation, and retinal ganglion cell polarization, yet it is unknown what role laminin might play in the early process of optic cup formation subsequent to the initial step of optic vesicle evagination. Here, we use the zebrafish lama1 mutant (lama1(UW1)) to determine the function of laminin during optic cup morphogenesis. Using live imaging, we find, surprisingly, that loss of laminin leads to divergent effects on focal adhesion assembly in a spatiotemporally-specific manner, and that laminin is required for multiple steps of optic cup morphogenesis, including optic stalk constriction, invagination, and formation of a spherical lens. Laminin is not required for single cell behaviors and changes in cell shape. Rather, in lama1(UW1) mutants, loss of epithelial polarity and altered adhesion lead to defective tissue architecture and formation of a disorganized retina. These results demonstrate that the laminin extracellular matrix plays multiple critical roles regulating adhesion and polarity to establish and maintain tissue structure during optic cup morphogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Egfl6 is involved in zebrafish notochord development.

    PubMed

    Wang, Xueqian; Wang, Xin; Yuan, Wei; Chai, Renjie; Liu, Dong

    2015-08-01

    The epidermal growth factor (EGF) repeat motif defines a superfamily of diverse protein involved in regulating a variety of cellular and physiological processes, such as cell cycle, cell adhesion, proliferation, migration, and neural development. Egfl6, an EGF protein, also named MAGE was first cloned in human tissue. Up to date, the study of zebrafish Egfl6 expression pattern and functional analysis of Egfl6 involved in embryonic development of vertebrate in vivo is thus far lacking. Here we reported that Egfl6 was involved in zebrafish notochord development. It was shown that Egfl6 mRNA was expressed in zebrafish, developing somites, fin epidermis, pharyngeal arches, and hindbrain region. Particularly the secreted Egfl6 protein was significantly accumulated in notochord. Loss of Egfl6 function in zebrafish embryos resulted in curved body with distorted notochord in the posterior trunk. It was observed that expression of all Notch ligand and receptors in notochord of 28 hpf Egfl6 morphants was not affected, except notch2, which was up-regulated. We found that inhibition of Notch signaling by DAPT efficiently rescued notochord developmental defect of Egfl6 deficiency embryos.

  10. Transient infection of the zebrafish notochord with E. coli induces chronic inflammation

    PubMed Central

    Nguyen-Chi, Mai; Phan, Quang Tien; Gonzalez, Catherine; Dubremetz, Jean-François; Levraud, Jean-Pierre; Lutfalla, Georges

    2014-01-01

    Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils) during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation. PMID:24973754

  11. Antennas of organ morphogenesis: the roles of cilia in vertebrate kidney development

    PubMed Central

    Marra, Amanda N.; Li, Yue

    2016-01-01

    Abstract Cilia arose early during eukaryotic evolution, and their structural components are highly conserved from the simplest protists to complex metazoan species. In recent years, the role of cilia in the ontogeny of vertebrate organs has received increasing attention due to a staggering correlation between human disease and dysfunctional cilia. In particular, the presence of cilia in both the developing and mature kidney has become a deep area of research due to ciliopathies common to the kidney, such as polycystic kidney disease (PKD). Interestingly, mutations in genes encoding proteins that localize to the cilia cause similar cystic phenotypes in kidneys of various vertebrates, suggesting an essential role for cilia in kidney organogenesis and homeostasis as well. Importantly, the genes so far identified in kidney disease have conserved functions across species, whose kidneys include both primary and motile cilia. Here, we aim to provide a comprehensive description of cilia and their role in kidney development, as well as highlight the usefulness of the zebrafish embryonic kidney as a model to further understand the function of cilia in kidney health. PMID:27389733

  12. Sox11 Is Required to Maintain Proper Levels of Hedgehog Signaling during Vertebrate Ocular Morphogenesis

    PubMed Central

    Pillai-Kastoori, Lakshmi; Wen, Wen; Wilson, Stephen G.; Strachan, Erin; Lo-Castro, Adriana; Fichera, Marco; Musumeci, Sebastiano A.; Lehmann, Ordan J.; Morris, Ann C.

    2014-01-01

    Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC) and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders. PMID:25010521

  13. Function of the Evx-2 gene in the morphogenesis of vertebrate limbs.

    PubMed Central

    Hérault, Y; Hraba-Renevey, S; van der Hoeven, F; Duboule, D

    1996-01-01

    Vertebrate gene members of the HoxD complex are essential for proper development of the appendicular skeletons. Inactivation of these genes induces severe alterations in the size and number of bony elements. Evx-2, a gene related to the Drosophila even-skipped (eve) gene, is located close to Hoxd-13 and is expressed in limbs like the neighbouring Hoxd genes. To investigate whether this tight linkage reflects a functional similarity, we produced a null allele of Evx-2. Furthermore, and because Hoxd-13 function is prevalent over that of nearby Hoxd genes, we generated two different double mutant loci wherein both Evx-2 and Hoxd-13 were inactivated in cis. The analysis of these various genetic configurations revealed the important function of Evx-2 during the development of the autopod as well as its genetic interaction with Hoxd-13. These results show that, in limbs, Evx-2 functions like a Hoxd gene. A potential evolutionary scenario is discussed, in which Evx-2 was recruited by the HoxD complex in conjunction with the emergence of digits in an ancestral tetrapod. Images PMID:8978698

  14. Did the notochord evolve from an ancient axial muscle? The axochord hypothesis

    PubMed Central

    Brunet, Thibaut; Lauri, Antonella

    2015-01-01

    The origin of the notochord is one of the key remaining mysteries of our evolutionary ancestry. Here, we present a multi‐level comparison of the chordate notochord to the axochord, a paired axial muscle spanning the ventral midline of annelid worms and other invertebrates. At the cellular level, comparative molecular profiling in the marine annelids P. dumerilii and C. teleta reveals expression of similar, specific gene sets in presumptive axochordal and notochordal cells. These cells also occupy corresponding positions in a conserved anatomical topology and undergo similar morphogenetic movements. At the organ level, a detailed comparison of bilaterian musculatures reveals that most phyla form axochord‐like muscles, suggesting that such a muscle was already present in urbilaterian ancestors. Integrating comparative evidence at the cell and organ level, we propose that the notochord evolved by modification of a ventromedian muscle followed by the assembly of an axial complex supporting swimming in vertebrate ancestors. PMID:26172338

  15. Apoptosis regulates notochord development in Xenopus

    PubMed Central

    Malikova, Marina; Van Stry, Melanie

    2009-01-01

    The notochord is the defining characteristic of the chordate embryo, and plays critical roles as a signaling center and as the primitive skeleton. In this study we show that early notochord development in Xenopus embryos is regulated by apoptosis. We find apoptotic cells in the notochord beginning at the neural groove stage and increasing in number as the embryo develops. These dying cells are distributed in an anterior to posterior pattern that is correlated with notochord extension through vacuolization. In axial mesoderm explants, inhibition of this apoptosis causes the length of the notochord to approximately double compared to controls. In embryos however, inhibition of apoptosis decreases the length of the notochord and it is severely kinked. This kinking also spreads from the anterior with developmental stage such that by the tadpole stage, the notochord lacks any recognizable structure, although notochord markers are expressed in a normal temporal pattern. Extension of the somites and neural plate mirror that of the notochord in these embryos, and the somites are severely disorganized. These data indicate that apoptosis is required for normal notochord development during the formation of the anterior-posterior axis, and its role in this process is discussed. PMID:17920580

  16. Wnt5 is required for notochord cell intercalation in the ascidian Halocynthia roretzi

    PubMed Central

    Niwano, Tomoko; Takatori, Naohito; Kumano, Gaku; Nishida, Hiroki

    2009-01-01

    Background information. In the embryos of various animals, the body elongates after gastrulation by morphogenetic movements involving convergent extension. The Wnt/PCP (planar cell polarity) pathway plays roles in this process, particularly mediolateral polarization and intercalation of the embryonic cells. In ascidians, several factors in this pathway, including Wnt5, have been identified and found to be involved in the intercalation process of notochord cells. Results. In the present study, the role of the Wnt5 genes, Hr-Wnt5α (Halocynthia roretzi Wnt5α) and Hr-Wnt5β, in convergent extension was investigated in the ascidian H. roretzi by injecting antisense oligonucleotides and mRNAs into single precursor blastomeres of various tissues, including notochord, at the 64-cell stage. Hr-Wnt5α is expressed in developing notochord and was essential for notochord morphogenesis. Precise quantitative control of its expression level was crucial for proper cell intercalation. Overexpression of Wnt5 proteins in notochord and other tissues that surround the notochord indicated that Wnt5α plays a role within the notochord, and is unlikely to be the source of polarizing cues arising outside the notochord. Detailed mosaic analysis of the behaviour of individual notochord cells overexpressing Wnt5α indicated that a Wnt5α-manipulated cell does not affect the behaviour of neighbouring notochord cells, suggesting that Wnt5α works in a cell-autonomous manner. This is further supported by comparison of the results of Wnt5α and Dsh (Dishevelled) knockdown experiments. In addition, our results suggest that the Wnt/PCP pathway is also involved in mediolateral intercalation of cells of the ventral row of the nerve cord (floor plate) and the endodermal strand. Conclusion. The present study highlights the role of the Wnt5α signal in notochord convergent extension movements in ascidian embryos. Our results raise the novel possibility that Wnt5α functions in a cell-autonomous manner

  17. How was the notochord born?

    PubMed

    Satoh, Nori; Tagawa, Kuni; Takahashi, Hiroki

    2012-01-01

    More than 550 million years ago, chordates originated from a common ancestor shared with nonchordate deuterostomes by developing a novel type of larva, the "tadpole larva." The notochord is the supporting organ of the larval tail and the most prominent feature of chordates; indeed, phylum Chordata is named after this organ. In this review, we discuss the molecular mechanisms involved in the formation of the notochord over the course of chordate evolution with a special emphasis on a member of T-box gene family, Brachyury. Comparison of the decoded genome of a unicellular choanoflagellate with the genomes of sponge and cnidarians suggests that T-box gene family arose at the time of the evolution of multicellular animals. Gastrulation is a morphogenetic movement that is essential for the formation of two- or three-germ-layered embryos. Brachyury is transiently expressed in the blastopore (bp) region, where it confers on cells the ability to undergo invagination. This process is involved in the formation of the archenteron in all metazoans. This is a "primary" function of Brachyury. During the evolution of chordates, Brachyury gained an additional expression domain at the dorsal midline region of the bp. In this new expression domain, Brachyury served its "secondary" function, recruiting another set of target genes to form a dorsal axial organ, notochord. The Wnt/β-catenin, BMP/Nodal, and FGF-signaling pathways are involved in the transcriptional activation of Brachyury. We discuss the molecular mechanisms of Brachyury secondary function in the context of the dorsal-ventral (D-V) inversion theory and the aboral-dorsalization hypothesis. Although the scope of this review requires some degree of oversimplification of Brachyury function, it is beneficial to facilitate studies on the notochord formation, a central evolutionary developmental biology problem in the history of metazoan evolution, pointed out first by Alexander Kowalevsky.

  18. Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis† †Electronic supplementary information (ESI) available: Figure showing the of effect of 5 and 6 on the notochord and experimental details for compounds 2–6. See DOI: 10.1039/b613673g Click here for additional data file.

    PubMed Central

    Anderson, Carrie; Bartlett, Stephen J.; Gansner, John M.; Wilson, Duncan; He, Ling; Gitlin, Jonathan D.

    2007-01-01

    As a result of a chemical genetic screen for modulators of metalloprotease activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan mutant. The location of the chemically-induced wavy notochord correlated with the timing of application, thus defining a narrow chemical sensitivity window during segmentation stages. Microscopic observations revealed that notochord undulations appeared during the phase of notochord cell vacuolation and notochord elongation. Notochord cells become swollen as well as disorganized, while electron microscopy revealed disrupted organization of collagen fibrils in the surrounding sheath. We demonstrate by assay in zebrafish extracts that 2-mercaptopyridine-N-oxide inhibits lysyl oxidase. Thus, we provide insight into notochord morphogenesis and reveal novel compounds for lysyl oxidase inhibition. Taken together, these data underline the utility of small molecules for elucidating the dynamic mechanisms of early morphogenesis and provide a potential explanation for the recently established role of copper in zebrafish notochord formation. PMID:17216056

  19. Vertebrate Axial Patterning: From Egg to Asymmetry.

    PubMed

    Houston, Douglas W

    2017-01-01

    The emergence of the bilateral embryonic body axis from a symmetrical egg has been a long-standing question in developmental biology. Historical and modern experiments point to an initial symmetry-breaking event leading to localized Wnt and Nodal growth factor signaling and subsequent induction and formation of a self-regulating dorsal "organizer." This organizer forms at the site of notochord cell internalization and expresses primarily Bone Morphogenetic Protein (BMP) growth factor antagonists that establish a spatiotemporal gradient of BMP signaling across the embryo, directing initial cell differentiation and morphogenesis. Although the basics of this model have been known for some time, many of the molecular and cellular details have only recently been elucidated and the extent that these events remain conserved throughout vertebrate evolution remains unclear. This chapter summarizes historical perspectives as well as recent molecular and genetic advances regarding: (1) the mechanisms that regulate symmetry-breaking in the vertebrate egg and early embryo, (2) the pathways that are activated by these events, in particular the Wnt pathway, and the role of these pathways in the formation and function of the organizer, and (3) how these pathways also mediate anteroposterior patterning and axial morphogenesis. Emphasis is placed on comparative aspects of the egg-to-embryo transition across vertebrates and their evolution. The future prospects for work regarding self-organization and gene regulatory networks in the context of early axis formation are also discussed.

  20. Stepwise enforcement of the notochord and its intersection with the myoseptum: an evolutionary path leading to development of the vertebra?

    PubMed Central

    Grotmol, Sindre; Kryvi, Harald; Keynes, Roger; Krossøy, Christel; Nordvik, Kari; Totland, Geir K

    2006-01-01

    The notochord constitutes the main axial support during the embryonic and larval stages, and the arrangement of collagen fibrils within the notochord sheath is assumed to play a decisive role in determining its functional properties as a fibre-wound hydrostatic skeleton. We have found that during early ontogeny in Atlantic salmon stepwise changes occur in the configuration of the collagen fibre-winding of the notochord sheath. The sheath consists of a basal lamina, a layer of type II collagen, and an elastica externa that delimits the notochord; and these constituents are secreted in a specific order. Initially, the collagen fibrils are circumferentially arranged perpendicular to the longitudinal axis, and this specific spatial fibril configuration is maintained until hatching when the collagen becomes reorganized into distinct layers or lamellae. Within each lamella, fibrils are parallel to each other, forming helices around the longitudinal axis of the notochord, with a tangent angle of 75–80° to the cranio-caudal axis. The helical geometry shifts between adjacent lamellae, forming enantiomorphous left- and right-handed coils, respectively, thus enforcing the sheath. The observed changes in the fibre-winding configuration may reflect adaptation of the notochord to functional demands related to stage in ontogeny. When the vertebral bodies initially form as chordacentra, the collagen lamellae of the sheath in the vertebral region are fixed by the deposition of minerals; in the intervertebral region, however, they represent a pre-adaptation providing torsional stability to the intervertebral joint. Hence, these modifications of the sheath transform the notochord per se into a functional vertebral column. The elastica externa, encasing the notochord, has serrated surfaces, connected inward to the type II collagen of the sheath, and outward to type I collagen of the mesenchymal connective tissue surrounding the notochord. In a similar manner, the collagen matrix of

  1. 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.

  2. Ptychoderid hemichordate neurulation without a notochord.

    PubMed

    Luttrell, Shawn; Konikoff, Charlotte; Byrne, Alana; Bengtsson, Barbara; Swalla, Billie J

    2012-12-01

    Enteropneust hemichordates share several characteristics with chordates, such as a Hox-specified anterior-posterior axis, pharyngeal gill slits, a dorsal central nervous system (CNS), and a juvenile postanal tail. Ptychoderid hemichordates, such as the indirect-developer Ptychodera flava, have feeding larvae and a remarkable capacity to regenerate their CNS. We compared neurulation of ptychoderid hemichordates and chordates using histological analyses, and found many similarities in CNS development. In ptychoderid hemichordates, which lack a notochord, the proboscis skeleton develops from endoderm after neurulation. The position of the proboscis skeleton directly under the nerve cord suggests that it serves a structural role similar to the notochord of chordates. These results suggest that either the CNS preceded evolution of the notochord or that the notochord has been lost in hemichordates. The evolution of the notochord remains ambiguous, but it may have evolved from endoderm, not mesoderm.

  3. 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

    2017-07-25

    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.

  4. Functional Brachyury Binding Sites Establish a Temporal Read-out of Gene Expression in the Ciona Notochord

    PubMed Central

    Passamaneck, Yale J.; Gazdoiu, Stefan; José-Edwards, Diana S.; Kugler, Jamie E.; Oda-Ishii, Izumi; Imai, Janice H.; Nibu, Yutaka; Di Gregorio, Anna

    2013-01-01

    The appearance of the notochord represented a milestone in Deuterostome evolution. The notochord is necessary for the development of the chordate body plan and for the formation of the vertebral column and numerous organs. It is known that the transcription factor Brachyury is required for notochord formation in all chordates, and that it controls transcription of a large number of target genes. However, studies of the structure of the cis-regulatory modules (CRMs) through which this control is exerted are complicated in vertebrates by the genomic complexity and the pan-mesodermal expression territory of Brachyury. We used the ascidian Ciona, in which the single-copy Brachyury is notochord-specific and CRMs are easily identifiable, to carry out a systematic characterization of Brachyury-downstream notochord CRMs. We found that Ciona Brachyury (Ci-Bra) controls most of its targets directly, through non-palindromic binding sites that function either synergistically or individually to activate early- and middle-onset genes, respectively, while late-onset target CRMs are controlled indirectly, via transcriptional intermediaries. These results illustrate how a transcriptional regulator can efficiently shape a shallow gene regulatory network into a multi-tiered transcriptional output, and provide insights into the mechanisms that establish temporal read-outs of gene expression in a fast-developing chordate embryo. PMID:24204212

  5. Essential role of lysyl oxidases in notochord development

    PubMed Central

    Gansner, John M.; Mendelsohn, Bryce A.; Hultman, Keith A.; Johnson, Stephen L.; Gitlin, Jonathan D.

    2007-01-01

    Recent studies reveal a critical role for copper in the development of the zebrafish notochord, suggesting that specific cuproenzymes are required for the structural integrity of the notochord sheath. We now demonstrate that β-aminopropionitrile, a known inhibitor of the copper-dependent lysyl oxidases, causes notochord distortion in the zebrafish embryo identical to that seen in copper deficiency. Characterization of the zebrafish lysyl oxidase genes reveals eight unique sequences, several of which are expressed in the developing notochord. Specific gene knockdown demonstrates that loss of loxl1 results in notochord distortion, and that loxl1 and loxl5b have overlapping roles in notochord formation. Interestingly, while notochord abnormalities are not observed following partial knockdown of loxl1 or loxl5b alone, in each case this markedly sensitizes developing embryos to notochord distortion if copper availability is diminished. Likewise, partial knockdown of the lysyl oxidase substrate col2a1 results in notochord distortion when combined with reduced copper availability or partial knockdown of loxl1 or loxl5b. These data reveal a complex interplay of gene expression and nutrient availability critical to notochord development. They also provide insight into specific genetic and nutritional factors that may play a role in the pathogenesis of structural birth defects of the axial skeleton. PMID:17543297

  6. Prenatal Evidence of Persistent Notochord and Absent Sacrum Caused by a Mutation in the T (Brachyury) Gene

    PubMed Central

    van Maarle, M. C.; Robles de Medina, P.; Oostra, R. J.; van Rijn, R. R.; Pajkrt, E.; Bilardo, C. M.

    2016-01-01

    Caudal regression syndrome (CRS) is a rare congenital disorder characterized by developmental abnormalities of caudal spinal segments. To date, the etiology of CRS is unclear; sporadic cases are strongly associated with maternal diabetes, while familiar recurrence is infrequent. We describe in detail the prenatal clinical and sonographic findings of a recently described hereditary caudal regression syndrome, in four fetuses reported to be homozygous for a mutation in the T (brachyury) gene. The syndrome occurred in three consanguineous, but unrelated families, originating from the same geographical area. All affected fetuses had persistence of the notochord in association with abnormal vertebral ossification, sacral agenesis, and bilateral clubfoot. These findings suggest that, in case of prenatal diagnosis of sacral agenesis, an advanced ultrasound examination should assess the vertebral ossification and the rare persistence of the notochord, in order to rule the involvement of the T gene. PMID:28116192

  7. An adhesome comprising laminin, dystroglycan and myosin IIA is required during notochord development in Xenopus laevis.

    PubMed

    Buisson, Nicolas; Sirour, Cathy; Moreau, Nicole; Denker, Elsa; Le Bouffant, Ronan; Goullancourt, Aline; Darribère, Thierry; Bello, Valérie

    2014-12-01

    Dystroglycan (Dg) is a transmembrane receptor for laminin that must be expressed at the right time and place in order to be involved in notochord morphogenesis. The function of Dg was examined in Xenopus laevis embryos by knockdown of Dg and overexpression and replacement of the endogenous Dg with a mutated form of the protein. This analysis revealed that Dg is required for correct laminin assembly, for cell polarization during mediolateral intercalation and for proper differentiation of vacuoles. Using mutations in the cytoplasmic domain, we identified two sites that are involved in cell polarization and are required for mediolateral cell intercalation, and a site that is required for vacuolation. Furthermore, using a proteomic analysis, the cytoskeletal non-muscle myosin IIA has been identified for the first time as a molecular link between the Dg-cytoplasmic domain and cortical actin. The data allowed us to identify the adhesome laminin-Dg-myosin IIA as being required to maintain the cortical actin cytoskeleton network during vacuolation, which is crucial to maintain the shape of notochordal cells.

  8. Chondroitin 4-O-sulfotransferases are required for cell adhesion and morphogenesis in the Ciona intestinalis embryo.

    PubMed

    Nakamura, Jun; Tetsukawa, Akira; Fujiwara, Shigeki

    2015-01-01

    Chondroitin sulfate (CS) is a carbohydrate component of proteoglycans. Several types of sulfotransferases determine the pattern of CS sulfation, and thus regulate the biological functions of proteoglycans. The protochordate ascidians are the closest relatives of vertebrates, but the functions of their sulfotransferases have not been investigated. Here, we show that two chondroitin 4-O-sulfotransferases (C4STs) play important roles in the embryonic morphogenesis of the ascidian Ciona intestinalis. Ci-C4ST-like1 is predominantly expressed in the epidermis and muscle. Epidermal and muscle cells became spherical upon the injection of a Ci-C4ST-like1-specific morpholino oligo (MO), thus suggesting weakened cell adhesion. Co-injection of a Ci-C4ST-like1-expressing transgene rescued the phenotype, suggesting that the effects of the MO were specific. Ci-C4ST-like3 was expressed in the central nervous system, muscle, and mesenchyme. A specific MO appeared to affect cell adhesion in the epidermis and muscle. Convergent extension movement of notochordal cells was also impaired. Forced expression of Ci-C4ST-like3 restored normal morphogenesis, suggesting that the effects of the MO were specific. The present study suggests that Ci-C4ST-like1 and Ci-C4ST-like3 are required for cell adhesion mainly in the epidermis and muscle.

  9. Digital development and morphogenesis

    PubMed Central

    Sanz-Ezquerro, JJ; Tickle, C

    2003-01-01

    Signalling interactions between the polarizing region, which produces SHH, and the apical ectodermal ridge, which produces FGFs, are essential for outgrowth and patterning of vertebrate limbs. However, mechanisms that mediate translation of early positional information of cells into anatomy remain largely unknown. In particular, the molecular and cellular basis of digit morphogenesis are not fully understood, either in terms of the formation of the different digits along the antero-posterior axis or in the way digits stop growing once pattern formation has been completed. Here we will review recent data about digit development. Manipulation of morphogenetic signals during digit formation, including application of SHH interdigitally, has shown that digit primordia possess a certain plasticity, and that digit anatomy becomes irreversibly fixed during morphogenesis. The process of generation of joints and thus segmentation and formation of digit tips is also discussed. PMID:12587920

  10. Vertebrate Lrig3-ErbB Interactions Occur In Vitro but Are Unlikely to Play a Role in Lrig3-Dependent Inner Ear Morphogenesis

    PubMed Central

    Abraira, Victoria E.; Satoh, Takunori; Fekete, Donna M.; Goodrich, Lisa V.

    2010-01-01

    Background The Lrig genes encode a family of transmembrane proteins that have been implicated in tumorigenesis, psoriasis, neural crest development, and complex tissue morphogenesis. Whether these diverse phenotypes reflect a single underlying cellular mechanism is not known. However, Lrig proteins contain evolutionarily conserved ectodomains harboring both leucine-rich repeats and immunoglobulin domains, suggesting an ability to bind to common partners. Previous studies revealed that Lrig1 binds to and inhibits members of the ErbB family of receptor tyrosine kinases by inducing receptor internalization and degradation. In addition, other receptor tyrosine kinase binding partners have been identified for both Lrig1 and Lrig3, leaving open the question of whether defective ErbB signaling is responsible for the observed mouse phenotypes. Methodology/Principal Findings Here, we report that Lrig3, like Lrig1, is able to interact with ErbB receptors in vitro. We examined the in vivo significance of these interactions in the inner ear, where Lrig3 controls semicircular canal formation by determining the timing and extent of Netrin1 expression in the otic vesicle epithelium. We find that ErbB2 and ErbB3 are present in the early otic epithelium, and that Lrig3 acts cell-autonomously here, as would be predicted if Lrig3 regulates ErbB2/B3 activity. However, inhibition of ErbB activation in the chick otic vesicle has no detectable effect on Netrin gene expression or canal morphogenesis. Conclusions/Significance Our results suggest that although both Lrig1 and Lrig3 can interact with ErbB receptors in vitro, modulation of Neuregulin signaling is unlikely to contribute to Lrig3-dependent processes of inner ear morphogenesis. These results highlight the similar binding properties of Lrig1 and Lrig3 and underscore the need to determine how these two family members bind to and regulate different receptors to affect diverse aspects of cell behavior in vivo. PMID:20126551

  11. Notochordal Cell-Derived Therapeutic Strategies for Discogenic Back Pain

    PubMed Central

    Purmessur, D.; Cornejo, M. C.; Cho, S. K.; Hecht, A. C.; Iatridis, J. C.

    2013-01-01

    An understanding of the processes that occur during development of the intervertebral disk can help inform therapeutic strategies for discogenic pain. This article reviews the literature to identify candidates that are found in or derived from the notochord or notochordal cells and evaluates the theory that such factors could be isolated and used as biologics to target the structural disruption, inflammation, and neurovascular ingrowth often associated with discogenic back pain. A systematic review using PubMed was performed with a primary search using keywords “(notochordal OR notochord) And (nerves OR blood vessels OR SHH OR chondroitin sulfate OR notch OR CTGF) NOT chordoma.” Secondary searches involved keywords associated with the intervertebral disk and pain. Several potential therapeutic candidates from the notochord and their possible targets were identified. Studies are needed to further identify candidates, explore mechanisms for effect, and to validate the theory that these candidates can promote structural restoration and limit or inhibit neurovascular ingrowth using in vivo studies. PMID:24436871

  12. 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

  13. Vertebral Development in Paleozoic and Mesozoic Tetrapods Revealed by Paleohistological Data.

    PubMed

    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 mass

  14. 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.

  15. Loss of col8a1a Function during Zebrafish Embryogenesis Results in Congenital Vertebral Malformations

    PubMed Central

    Gray, Ryan S.; Wilm, Thomas; Smith, Jeff; Bagnat, Michel; Dale, Rodney M.; Topczewski, Jacek; Johnson, Stephen L.; Solnica-Krezel, Lilianna

    2014-01-01

    Congenital vertebral malformations (CVM) occur in 1 in 1,000 live births and in many cases can cause spinal deformities, such as scoliosis, and result in disability and distress of affected individuals. Many severe forms of the disease, such as spondylocostal dystostosis, are recessive monogenic traits affecting somitogenesis, however the etiologies of the majority of CVM cases remain undetermined. Here we demonstrate that morphological defects of the notochord in zebrafish can generate congenital-type spine defects. We characterize three recessive zebrafish leviathan/col8a1a mutant alleles (m531, vu41, vu105) that disrupt collagen type VIII alpha1a (col8a1a), and cause folding of the embryonic notochord and consequently adult vertebral column malformations. Furthermore, we provide evidence that a transient loss of col8a1a function or inhibition of Lysyl oxidases with drugs during embryogenesis was sufficient to generate vertebral fusions and scoliosis in the adult spine. Using periodic imaging of individual zebrafish, we correlate focal notochord defects of the embryo with vertebral malformations (VM) in the adult. Finally, we show that bends and kinks in the notochord can lead to aberrant apposition of osteoblasts normally confined to well-segmented areas of the developing vertebral bodies. Our results afford a novel mechanism for the formation of VM, independent of defects of somitogenesis, resulting from aberrant bone deposition at regions of misshapen notochord tissue. PMID:24333517

  16. Picornavirus Morphogenesis

    PubMed Central

    Jiang, Ping; Liu, Ying; Ma, Hsin-Chieh; Paul, Aniko V.

    2014-01-01

    SUMMARY The Picornaviridae represent a large family of small plus-strand RNA viruses that cause a bewildering array of important human and animal diseases. Morphogenesis is the least-understood step in the life cycle of these viruses, and this process is difficult to study because encapsidation is tightly coupled to genome translation and RNA replication. Although the basic steps of assembly have been known for some time, very few details are available about the mechanism and factors that regulate this process. Most of the information available has been derived from studies of enteroviruses, in particular poliovirus, where recent evidence has shown that, surprisingly, the specificity of encapsidation is governed by a viral protein-protein interaction that does not involve an RNA packaging signal. In this review, we make an attempt to summarize what is currently known about the following topics: (i) encapsidation intermediates, (ii) the specificity of encapsidation (iii), viral and cellular factors that are required for encapsidation, (iv) inhibitors of encapsidation, and (v) a model of enterovirus encapsidation. Finally, we compare some features of picornavirus morphogenesis with those of other plus-strand RNA viruses. PMID:25184560

  17. Beyond cell proliferation in avian facial morphogenesis

    PubMed Central

    Linde-Medina, Marta; Hallgrímsson, Benedikt; Marcucio, Ralph

    2016-01-01

    The upper jaw in vertebrates forms from several prominences that arise around the stomodeum or primitive mouth. These prominences undergo coordinated growth and morphogenesis to fuse and form the face. Undirected, regionalized cell proliferation is thought to be the driving force behind the morphogenesis of the facial prominences. However, recent findings suggest that directed cell behaviors in the mesenchyme (e.g., directed cell division, directed cell movement, convergent extension) might be required for successful face formation. Here we discuss the evidence for this view and how directed behaviors may interact with the basement membrane to regulate morphogenesis of the facial region. We believe that future research in these largely unexplored areas could significantly impact our understanding of facial morphogenesis. PMID:26637960

  18. Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus.

    PubMed

    Merceron, Christophe; Mangiavini, Laura; Robling, Alexander; Wilson, Tremika LeShan; Giaccia, Amato J; Shapiro, Irving M; Schipani, Ernestina; Risbud, Makarand V

    2014-01-01

    The intervertebral disc (IVD) is one of the largest avascular organs in vertebrates. The nucleus pulposus (NP), a highly hydrated and proteoglycan-enriched tissue, forms the inner portion of the IVD. The NP is surrounded by a multi-lamellar fibrocartilaginous structure, the annulus fibrosus (AF). This structure is covered superior and inferior side by cartilaginous endplates (CEP). The NP is a unique tissue within the IVD as it results from the differentiation of notochordal cells, whereas, AF and CEP derive from the sclerotome. The hypoxia inducible factor-1α (HIF-1α) is expressed in NP cells but its function in NP development and homeostasis is largely unknown. We thus conditionally deleted HIF-1α in notochordal cells and investigated how loss of this transcription factor impacts NP formation and homeostasis at E15.5, birth, 1 and 4 months of age, respectively. Histological analysis, cell lineage studies, and TUNEL assay were performed. Morphologic changes of the mutant NP cells were identified as early as E15.5, followed, postnatally, by the progressive disappearance and replacement of the NP with a novel tissue that resembles fibrocartilage. Notably, lineage studies and TUNEL assay unequivocally proved that NP cells did not transdifferentiate into chondrocyte-like cells but they rather underwent massive cell death, and were completely replaced by a cell population belonging to a lineage distinct from the notochordal one. Finally, to evaluate the functional consequences of HIF-1α deletion in the NP, biomechanical testing of mutant IVD was performed. Loss of the NP in mutant mice significantly reduced the IVD biomechanical properties by decreasing its ability to absorb mechanical stress. These findings are similar to the changes usually observed during human IVD degeneration. Our study thus demonstrates that HIF-1α is essential for NP development and homeostasis, and it raises the intriguing possibility that this transcription factor could be involved in IVD

  19. Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation

    PubMed Central

    Tsumaki, Noriyuki; Tanaka, Kazuhiro; Arikawa-Hirasawa, Eri; Nakase, Takanobu; Kimura, Tomoatsu; Thomas, J. Terrig; Ochi, Takahiro; Luyten, Frank P.; Yamada, Yoshihiko

    1999-01-01

    Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. Transgenic mice with targeted expression of recombinant cartilage-derived morphogenetic protein-1 (CDMP-1), a member of the bone morphogenetic protein family, were created to investigate the role of CDMP-1 in skeletal formation. The mice exhibited chondrodysplasia with expanded cartilage, which consists of the enlarged hypertrophic zone and the reduced proliferating chondrocyte zone. Histologically, CDMP-1 increased the number of chondroprogenitor cells and accelerated chondrocyte differentiation to hypertrophy. Expression of CDMP-1 in the notochord inhibited vertebral body formation by blocking migration of sclerotome cells to the notochord. These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord. Our study suggests a molecular mechanism by which CDMP-1 regulates the formation, growth, and differentiation of the skeletal elements. PMID:9885252

  20. The origin of developmental mechanisms underlying vertebral elements: implications from hagfish evo-devo.

    PubMed

    Ota, Kinya G; Oisi, Yasuhiro; Fujimoto, Satoko; Kuratani, Shigeru

    2014-02-01

    The origins of the vertebral elements and the underlying developmental mechanisms have so far remained unclear, largely due to the unusual axial skeletal morphology of hagfish, one of two extant jawless vertebrate clades. Hagfish axial supporting tissue is generally believed to consist of the notochord and cartilaginous fin rays only. However, careful investigations of whether vertebral elements are truly absent in hagfish are scarce, and it is also unclear whether the axial skeletal morphology of the hagfish is an ancestral or a derived condition. To address these questions, we re-examined the axial skeletal morphology of the Japanese inshore hagfish (Eptatretus burgeri). Based on a report published a century ago which implied the existence of vertebral elements in hagfish, we conducted anatomical and histological analyses of the hagfish axial skeletal systems and their development. Through this analysis, we demonstrate that hagfish possesses sclerotome-derived cartilaginous vertebral elements at the ventral aspect of the notochord. Based on (i) molecular phylogenetic evidence in support of the monophyly of cyclostomes (hagfish and lampreys) and jawed vertebrates (gnathostomes), and (ii) the morphology of the vertebral elements in extant gnathostomes and cyclostomes, we propose that the embryos of the common ancestor of all vertebrates would have possessed sclerotomal cells that formed the segmentally arranged vertebral elements attached to the notochord. We also conclude that the underlying developmental mechanisms are likely to have been conserved among extinct jawless vertebrates and modern gnathostomes. Copyright © 2013 Elsevier GmbH. All rights reserved.

  1. Species-specific contribution of volumetric growth and tissue convergence to posterior body elongation in vertebrates.

    PubMed

    Steventon, Ben; Duarte, Fernando; Lagadec, Ronan; Mazan, Sylvie; Nicolas, Jean-François; Hirsinger, Estelle

    2016-05-15

    Posterior body elongation is a widespread mechanism propelling the generation of the metazoan body plan. The posterior growth model predicts that a posterior growth zone generates sufficient tissue volume to elongate the posterior body. However, there are energy supply-related differences between vertebrates in the degree to which growth occurs concomitantly with embryogenesis. By applying a multi-scalar morphometric analysis in zebrafish embryos, we show that posterior body elongation is generated by an influx of cells from lateral regions, by convergence-extension of cells as they exit the tailbud, and finally by a late volumetric growth in the spinal cord and notochord. Importantly, the unsegmented region does not generate additional tissue volume. Fibroblast growth factor inhibition blocks tissue convergence rather than volumetric growth, showing that a conserved molecular mechanism can control convergent morphogenesis through different cell behaviours. Finally, via a comparative morphometric analysis in lamprey, dogfish, zebrafish and mouse, we propose that elongation via posterior volumetric growth is linked to increased energy supply and is associated with an overall increase in volumetric growth and elongation. © 2016. Published by The Company of Biologists Ltd.

  2. Isolation and characterization of node/notochord-like cells from mouse embryonic stem cells.

    PubMed

    Winzi, Maria K; Hyttel, Poul; Dale, Jacqueline Kim; Serup, Palle

    2011-11-01

    The homeobox gene Noto is expressed in the node and its derivative the notochord. Here we use a targeted Noto-GFP reporter to isolate and characterize node/notochord-like cells derived from mouse embryonic stem cells. We find very few Noto-expressing cells after spontaneous differentiation. However, the number of Noto-expressing cells was increased when using Activin A to induce a Foxa2- and Brachyury-expressing progenitor population, whose further differentiation into Noto-expressing cells was improved by simultaneous inhibition of BMP, Wnt, and retinoic acid signaling. Noto-GFP(+) cells expressed the node/notochord markers Noto, Foxa2, Shh, Noggin, Chordin, Foxj1, and Brachyury; showed a vacuolarization characteristic of notochord cells; and can integrate into midline structures when grafted into Hensen's node of gastrulating chicken embryos. The ability to generate node/notochord-like cells in vitro will aid the biochemical characterization of these developmentally important structures.

  3. Notochordal Cells Influence Gene Expression of Inflammatory Mediators of Annulus Fibrosus Cells in Proinflammatory Cytokines Stimulation

    PubMed Central

    Moon, Hong Joo; Joe, Hoon; Kwon, Taek Hyun; Choi, Hye-Kyoung; Park, Youn Kwan

    2010-01-01

    Objective Notochordal cells in the intervertebral disc interact with nucleus pulposus (NP) cells and support the maintenance of disc homeostasis by regulation of matrix production. However, the influence of notochordal cells has not been evaluated in the annulus fibrosus (AF), which is the primary pain generator in the disc. We hypothesized that the notochordal cell has the capacity to modulate inflammatory mediators secreted by AF cells secondary to stimulation. Methods Notochordal and AF cells were isolated from adult New Zealand white rabbits. AF pellets were cultured with notochordal cell clusters or in notochordal cell-conditioned media (NCCM) for 24 or 48 hours with proinflammatory cytokines at varying concentrations. Gene expression in AF pellets were assayed for nitric oxide synthase (iNOS), cyclo-oxygenase (COX)-2, and interleukin (IL)-6 by real time reverse transcriptase polymerase chain reaction (RT-PCR). Results AF pellet in NCCM significantly decreased the iNOS and COX-2 messenger ribonucleic acid (mRNA) levels compared to AF pellets alone and AF pellets with notochordal cells (p < 0.05). AF pellet resulted in dose-dependent iNOS and COX-2 expression in response to IL-1β, stimulation, demonstrating that 1 ng/ml for 24 hours yielded a maximal response. AF pellet in NCCM significantly decreased the expression of iNOS and COX-2 in response to 1ng/ml IL-1β, stimulation at 24 hours (p < 0.05). There was no difference in IL-6 expression compared to AF pellets alone or AF pellets with notochordal cell clusters. Conclusion We conclude that soluble factors from notochordal cells mitigate the gene expression of inflammatory mediators in stimulated AF, as expected after annular injury, suggesting that notochordal cells could serve as a novel therapeutic approach in symptomatic disc development. PMID:20717505

  4. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  5. The notochord curvature in medaka (Oryzias latipes) embryos as a response to ultraviolet A irradiation.

    PubMed

    Sayed, Alaa El-Din Hamid; Mitani, Hiroshi

    2016-11-01

    In the present work, the destructive effects of ultraviolet A (UVA; 366nm) irradiation on the developmental stages of Japanese medaka (Oryzias latipes) are revealed in terms of hatching success, mortality rate, and morphological malformations (yolk sac edema, body curvature, fin blistering, and dwarfism). Fertilized eggs in stage 4 were exposed to 15, 30, and 60min/day UVA for 3days in replicates. Fish were staged and aged following the stages established by Iwamatsu [1]. We observed and recorded the hatching time and deformed and dead embryos continuously. The hatching time was prolonged and the deformed and dead embryos numbers were increased by UVA dose increase. At stage 40, samples from each group were fixed to investigate their morphology and histopathology. Some morphological malformations were recorded after UVA exposure in both strains. Histopathological changes were represented as different shapes of curvature in notochord with collapse. The degree of collapsation was depended on the dose and time of UVA exposure. Our findings show that exposure to UVA irradiation caused less vertebral column curvature in medaka fry. Moreover, p53-deficient embryos were more tolerant than those of wild-type (Hd-rR) Japanese medaka. This study indicated the dangerous effects of the UVA on medaka. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Branching Morphogenesis

    PubMed Central

    Horowitz, Arie; Simons, Michael

    2009-01-01

    Tubular structures are a fundamental anatomical theme recurring in a wide range of animal species. In mammals, tubulogenesis underscores the development of several systems and organs, including the vascular system, the lungs, and the kidneys. All tubular systems are hierarchical, branching into segments of gradually diminishing diameter. There are only two cell types that form the lumen of tubular systems – either endothelial cells in the vascular system, or epithelial cells in all other organs. The most important feature in determining the morphology of the tubular systems is the frequency and geometry of branching. Hence, deciphering the molecular mechanisms underlying the sprouting of new branches from pre-existing ones is the key to understanding the formation of tubular systems. The morphological similarity between the various tubular systems is underscored by similarities between the signaling pathways which control their branching. A prominent feature common to these pathways is their duality – an agonist counterbalanced by an inhibitor. The formation of the tracheal system in Drosophila melanogaster is driven by fibroblast growth factor (FGF) and inhibited by Sprouty/Notch. In vertebrates, the analogous pathways are FGF and transforming growth factor β in epithelial tubular systems, or vascular endothelial growth factor and Notch in the vascular system. PMID:19179661

  7. FoxA4 Favours Notochord Formation by Inhibiting Contiguous Mesodermal Fates and Restricts Anterior Neural Development in Xenopus Embryos

    PubMed Central

    Murgan, Sabrina; Castro Colabianchi, Aitana Manuela; Monti, Renato José; Boyadjián López, Laura Elena; Aguirre, Cecilia E.; Stivala, Ernesto González; López, Silvia L.

    2014-01-01

    In vertebrates, the embryonic dorsal midline is a crucial signalling centre that patterns the surrounding tissues during development. Members of the FoxA subfamily of transcription factors are expressed in the structures that compose this centre. Foxa2 is essential for dorsal midline development in mammals, since knock-out mouse embryos lack a definitive node, notochord and floor plate. The related gene foxA4 is only present in amphibians. Expression begins in the blastula –chordin and –noggin expressing centre (BCNE) and is later restricted to the dorsal midline derivatives of the Spemann's organiser. It was suggested that the early functions of mammalian foxa2 are carried out by foxA4 in frogs, but functional experiments were needed to test this hypothesis. Here, we show that some important dorsal midline functions of mammalian foxa2 are exerted by foxA4 in Xenopus. We provide new evidence that the latter prevents the respecification of dorsal midline precursors towards contiguous fates, inhibiting prechordal and paraxial mesoderm development in favour of the notochord. In addition, we show that foxA4 is required for the correct regionalisation and maintenance of the central nervous system. FoxA4 participates in constraining the prospective rostral forebrain territory during neural specification and is necessary for the correct segregation of the most anterior ectodermal derivatives, such as the cement gland and the pituitary anlagen. Moreover, the early expression of foxA4 in the BCNE (which contains precursors of the whole forebrain and most of the midbrain and hindbrain) is directly required to restrict anterior neural development. PMID:25343614

  8. An amphioxus winged helix/forkhead gene, AmphiFoxD: insights into vertebrate neural crest evolution

    NASA Technical Reports Server (NTRS)

    Yu, Jr-Kai; Holland, Nicholas D.; Holland, Linda Z.

    2002-01-01

    During amphioxus development, the neural plate is bordered by cells expressing many genes with homologs involved in vertebrate neural crest induction. However, these amphioxus cells evidently lack additional genetic programs for the cell delaminations, migrations, and differentiations characterizing definitive vertebrate neural crest. We characterize an amphioxus winged helix/forkhead gene (AmphiFoxD) closely related to vertebrate FoxD genes. Phylogenetic analysis indicates that the AmphiFoxD is basal to vertebrate FoxD1, FoxD2, FoxD3, FoxD4, and FoxD5. One of these vertebrate genes (FoxD3) consistently marks neural crest during development. Early in amphioxus development, AmphiFoxD is expressed medially in the anterior neural plate as well as in axial (notochordal) and paraxial mesoderm; later, the gene is expressed in the somites, notochord, cerebral vesicle (diencephalon), and hindgut endoderm. However, there is never any expression in cells bordering the neural plate. We speculate that an AmphiFoxD homolog in the common ancestor of amphioxus and vertebrates was involved in histogenic processes in the mesoderm (evagination and delamination of the somites and notochord); then, in the early vertebrates, descendant paralogs of this gene began functioning in the presumptive neural crest bordering the neural plate to help make possible the delaminations and cell migrations that characterize definitive vertebrate neural crest. Copyright 2002 Wiley-Liss, Inc.

  9. Dynamics of cell polarity in tissue morphogenesis: a comparative view from Drosophila and Ciona.

    PubMed

    Veeman, Michael T; McDonald, Jocelyn A

    2016-01-01

    Tissues in developing embryos exhibit complex and dynamic rearrangements that shape forming organs, limbs, and body axes. Directed migration, mediolateral intercalation, lumen formation, and other rearrangements influence the topology and topography of developing tissues. These collective cell behaviors are distinct phenomena but all involve the fine-grained control of cell polarity. Here we review recent findings in the dynamics of polarized cell behavior in both the Drosophila ovarian border cells and the Ciona notochord. These studies reveal the remarkable reorganization of cell polarity during organ formation and underscore conserved mechanisms of developmental cell polarity including the Par/atypical protein kinase C (aPKC) and planar cell polarity pathways. These two very different model systems demonstrate important commonalities but also key differences in how cell polarity is controlled in tissue morphogenesis. Together, these systems raise important, broader questions on how the developmental control of cell polarity contributes to morphogenesis of diverse tissues across the metazoa.

  10. Composition of fluid from the notochordal canal of the coelacanth, Latimeria chalumnae.

    PubMed

    Griffith, R W; Mathews, M B; Umminger, B L; Grant, B F; Pang, P K; Thomson, K S; Pickford, G E

    1975-05-01

    Fluid from the notochordal canal of the coelacanth, Latimeria chalumnae, was analyzed for major inorganic and organic constituents and compared with blood serum from the same fish. Significantly or suggestively lower levels of sodium, magnesium, calcium, bicarbonate, sulfate, total carbohydrates, glucose, lactate, cholesterol, bound phosphate and total proteins were found in notochordal fluid than in serum, whereas potassium, chloride, urea, trimethylamine oxide, and total free amino acids were higher and inorganic phosphorus essentially identical. Osmolarity of notochordal fluid (1058 mOsm) exceeds that of serum (942 mOsm). A whitish precipitate in the fluid consisted of a matrix of fibers 100 A in diameter and of indefinite length. It resembled a sialoglycoprotein in composition and was stabilized by disulfide bonds. The fluid contained cellular debris.

  11. A one-dimensional model of PCP signaling: polarized cell behavior in the notochord of the ascidian Ciona.

    PubMed

    Kourakis, Matthew J; Reeves, Wendy; Newman-Smith, Erin; Maury, Benoit; Abdul-Wajid, Sarah; Smith, William C

    2014-11-01

    Despite its importance in development and physiology the planar cell polarity (PCP) pathway remains one of the most enigmatic signaling mechanisms. The notochord of the ascidian Ciona provides a unique model for investigating the PCP pathway. Interestingly, the notochord appears to be the only embryonic structure in Ciona activating the PCP pathway. Moreover, the Ciona notochord as a single-file array of forty polarized cells is a uniquely tractable system for the study of polarization dynamics and the transmission of the PCP pathway. Here, we test models for propagation of a polarizing signal, interrogating temporal, spatial and signaling requirements. A simple cell-cell relay cascading through the entire length of the notochord is not supported; instead a more complex mechanism is revealed, with interactions influencing polarity between neighboring cells, but not distant ones. Mechanisms coordinating notochord-wide polarity remain elusive, but appear to entrain general (i.e., global) polarity even while local interactions remain important. However, this global polarizer does not appear to act as a localized, spatially-restricted determinant. Coordination of polarity along the long axis of the notochord requires the PCP pathway, a role we demonstrate is temporally distinct from this pathway's earlier role in convergent extension and intercalation. We also reveal polarity in the notochord to be dynamic: a cell's polarity state can be changed and then restored, underscoring the Ciona notochord's amenability for in vivo studies of PCP. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Vertebral development and amphibian evolution.

    PubMed

    Carroll, R L; Kuntz, A; Albright, K

    1999-01-01

    Amphibians provide an unparalleled opportunity to integrate studies of development and evolution through the investigation of the fossil record of larval stages. The pattern of vertebral development in modern frogs strongly resembles that of Paleozoic labyrinthodonts in the great delay in the ossification of the vertebrae, with the centra forming much later than the neural arches. Slow ossification of the trunk vertebrae in frogs and the absence of ossification in the tail facilitate the rapid loss of the tail during metamorphosis, and may reflect retention of the pattern in their specific Paleozoic ancestors. Salamanders and caecilians ossify their centra at a much earlier stage than frogs, which resembles the condition in Paleozoic lepospondyls. The clearly distinct patterns and rates of vertebral development may indicate phylogenetic separation between the ultimate ancestors of frogs and those of salamanders and caecilians within the early radiation of ancestral tetrapods. This divergence may date from the Lower Carboniferous. Comparison with the molecular regulation of vertebral development described in modern mammals and birds suggests that the rapid chondrification of the centra in salamanders relative to that of frogs may result from the earlier migration of sclerotomal cells expressing Pax1 to the area surrounding the notochord.

  13. Muscular contractions in the zebrafish embryo are necessary to reveal thiuram-induced notochord distortions

    SciTech Connect

    Teraoka, Hiroki . E-mail: hteraoka@rakuno.ac.jp; Urakawa, Satsuki; Nanba, Satomi; Nagai, Yuhki; Wu Dong; Imagawa, Tomohiro; Tanguay, Robert L.; Svoboda, Kurt; Handley-Goldstone, Heather M.; Stegeman, John J.; Hiraga, Takeo

    2006-04-01

    Dithiocarbamates form a large group of chemicals that have numerous uses in agriculture and medicine. It has been reported that dithiocarbamates, including thiuram (tetramethylthiuram disulfide), cause wavy distortions of the notochord in zebrafish and other fish embryos. In the present study, we investigated the mechanism underlying the toxicity of thiuram in zebrafish embryos. When embryos were exposed to thiuram (2-1000 nM: 0.48-240 {mu}g/L) from 3 h post fertilization (hpf) (30% epiboly) until 24 hpf (Prim-5), all embryos develop wavy notochords, disorganized somites, and have shortened yolk sac extensions. The thiuram response was specific and did not cause growth retardation or mortality at 24 hpf. The thiuram-dependent responses showed the same concentration dependence with a waterborne EC{sub 5} values of approximately 7 nM. Morphometric measurements revealed that thiuram does not affect the rate of notochord lengthening. However, the rate of overall body lengthening was significantly reduced in thiuram-exposed animals. Other dithiocarbamates, such as ziram, caused similar malformations to thiuram. While expression of genes involved in somitogenesis was not affected, the levels of notochord-specific transcripts were altered after the onset of malformations. Distortion of the notochord started precisely at 18 hpf, which is concomitant with onset of spontaneous rhythmic trunk contractions. Abolishment of spontaneous contractions using tricaine, {alpha}-bungarotoxin, and a paralytic mutant sofa potato, resulted in normal notochord morphology in the presence of thiuram. These results indicate that muscle activity is necessary to reveal the underlying functional deficit and suggest that the developmental target of dithiocarbamates impairs trunk plasticity through an unknown mechanism.

  14. Mechanisms of thymus organogenesis and morphogenesis

    PubMed Central

    Gordon, Julie; Manley, Nancy R.

    2011-01-01

    The thymus is the primary organ responsible for generating functional T cells in vertebrates. Although T cell differentiation within the thymus has been an area of intense investigation, the study of thymus organogenesis has made slower progress. The past decade, however, has seen a renewed interest in thymus organogenesis, with the aim of understanding how the thymus develops to form a microenvironment that supports T cell maturation and regeneration. This has prompted modern revisits to classical experiments and has driven additional genetic approaches in mice. These studies are making significant progress in identifying the molecular and cellular mechanisms that control specification, early organogenesis and morphogenesis of the thymus. PMID:21862553

  15. [Neural crest and vertebrate evolution].

    PubMed

    Le Douarin, Nicole M; Creuzet, Sophie

    2011-01-01

    The neural crest (NC) is a remarkable structure of the Vertebrate embryo, which forms from the lateral borders of the neural plate (designated as neural folds) during neural tube closure. As soon as the NC is formed, its constitutive cells detach and migrate away from the neural primordium along definite pathways and at precise periods of time according to a rostro-caudal progression. The NC cells aggregate in definite places in the developing embryo, where they differentiate into a large variety of cell types including the neurons and glial cells of the peripheral nervous system, the pigment cells dispersed throughout the body and endocrine cells such as the adrenal medulla and the calcitonin producing cells. At the cephalic level only, in higher Vertebrates (but along the whole neural axis in Fishes and Amphibians), the NC is also at the origin of mesenchymal cells differentiating into connective tissue chondrogenic and osteogenic cells. Vertebrates belong to the larger group of Cordates which includes also the Protocordates (Cephalocordates and the Urocordates). All Cordates are characterized by the same body plan with a dorsal neural tube and a notochord which, in Vertebrates, exists only at embryonic stages. The main difference between Protocordates and Vertebrates is the very rudimentary development of cephalic structures in the former. As a result, the process of cephalization is one of the most obvious characteristics of Vertebrates. It was accompanied by the apparition of the NC which can therefore be considered as an innovation of Vertebrates during evolution. The application of a cell marking technique which consists in constructing chimeric embryos between two species of birds, the quail and the chicken, has led to show that the vertebrate head is mainly formed by cells originating from the NC, meaning that this structure was an important asset in Vertebrate evolution. Recent studies, described in this article, have strengthened this view by showing

  16. Dynamic epithelia of the developing vertebrate face.

    PubMed

    Choe, Chong Pyo; Crump, J Gage

    2015-06-01

    A segmental series of endoderm-derived pouch and ectoderm-derived cleft epithelia act as signaling centers in the developing face. Their precise morphogenesis is therefore essential for proper patterning of the vertebrate head. Intercellular adhesion and polarity are highly dynamic within developing facial epithelial cells, with signaling from the adjacent mesenchyme controlling both epithelial character and directional migration. Endodermal and ectodermal epithelia fuse to form the primary mouth and gill slits, which involves basement membrane dissolution, cell intercalations, and apoptosis, as well as undergo further morphogenesis to generate the middle ear cavity and glands of the neck. Recent studies of facial epithelia are revealing both core programs of epithelial morphogenesis and insights into the coordinated assembly of the vertebrate head.

  17. Craniofacial morphogenesis workshop report.

    PubMed

    Solursh, M; Murray, J

    1994-05-01

    The following report highlights the discussions and interaction at the workshop on craniofacial morphogenesis, sponsored by The Human Frontier Science Program, held in April 1993 at the University of Iowa. A brief summary of selected sessions is included to exemplify the benefits of bringing together individuals from various disciplines and backgrounds in order to establish a unified theory of craniofacial morphogenesis. The synthesis of information and experience of a wide range of approaches made the 4-day period an invaluable experience for the participants from nine different countries.

  18. Characterization of NF-κΒ/IκΒ Proteins in Zebra Fish and Their Involvement in Notochord Development

    PubMed Central

    Correa, Ricardo G.; Tergaonkar, Vinay; Ng, Jennifer K.; Dubova, Ilir; Izpisua-Belmonte, Juan Carlos; Verma, Inder M.

    2004-01-01

    Although largely involved in innate and adaptive immunity, NF-κB plays an important role in vertebrate development. In chicks, the inactivation of the NF-κΒ pathway induces functional alterations of the apical ectodermal ridge, which mediates limb outgrowth. In mice, the complete absence of NF-κB activity leads to prenatal death and neural tube defects. Here, we report the cloning and characterization of NF-κΒ/IκB proteins in zebra fish. Despite being ubiquitously expressed among the embryonic tissues, NF-κΒ/IκB members present distinct patterns of gene expression during the early zebra fish development. Biochemical assays indicate that zebra fish NF-κΒ proteins are able to bind consensus DNA-binding (κB) sites and inhibitory IκBα proteins from mammals. We show that zebra fish IκBαs are degraded in a time-dependent manner after induction of transduced murine embryo fibroblasts (MEFs) and that these proteins are able to rescue NF-κΒ activity in IκBα−/− MEFs. Expression of a dominant-negative form of the murine IκBα (mIκBαM), which is able to block NF-κΒ in zebra fish cells, interferes with the notochord differentiation, generating no tail (ntl)-like embryos. This phenotype can be rescued by coinjection of the T-box gene ntl (Brachyury homologue), which is typically required for the formation of posterior mesoderm and axial development, suggesting that ntl lies downstream of NF-κΒ. We further show that ntl and Brachyury promoter regions contain functional κB sites and NF-κΒ can directly modulate ntl expression. Our study illustrates the conservation and compatibility of NF-κΒ/IκB proteins among vertebrates and the importance of NF-κΒ pathway in mesoderm formation during early embryogenesis. PMID:15169890

  19. From Notochord Formation to Hereditary Chordoma: The Many Roles of Brachyury

    PubMed Central

    Nibu, Yutaka; José-Edwards, Diana S.; Di Gregorio, Anna

    2013-01-01

    Chordoma is a rare, but often malignant, bone cancer that preferentially affects the axial skeleton and the skull base. These tumors are both sporadic and hereditary and appear to occur more frequently after the fourth decade of life; however, modern technologies have increased the detection of pediatric chordomas. Chordomas originate from remnants of the notochord, the main embryonic axial structure that precedes the backbone, and share with notochord cells both histological features and the expression of characteristic genes. One such gene is Brachyury, which encodes for a sequence-specific transcription factor. Known for decades as a main regulator of notochord formation, Brachyury has recently gained interest as a biomarker and causative agent of chordoma, and therefore as a promising therapeutic target. Here, we review the main characteristics of chordoma, the molecular markers, and the clinical approaches currently available for the early detection and possible treatment of this cancer. In particular, we report on the current knowledge of the role of Brachyury and of its possible mechanisms of action in both notochord formation and chordoma etiogenesis. PMID:23662285

  20. Brachyury Essential for Notochord Cell Fate, Not Proliferation or EMT | Center for Cancer Research

    Cancer.gov

    The Brachyury or T gene encodes a transcription factor that is essential for body axis elongation during embryonic development. T is also highly expressed in chordomas, rare sarcomas derived from notochord cells, and a number of additional tumor types, including lung, prostate, and colon cancers. 

  1. A case of split notochord syndrome: Presenting with respiratory failure in the neonatal period

    PubMed Central

    Coskun, Yesim; Akman, Ipek; Demir, Mustafa Kemal; Yapicier, Ozlem; Somuncu, Salih

    2016-01-01

    Summary Split notochord syndrome (SNS) is a very rare congenital anomaly. This report describes a male newborn with a neuroenteric cyst in the posterior mediastinum and multiple vertebrae anomalies presenting with respiratory failure and pulmonary hypertension. This report also discusses the embryological development and the etiologic theories of SNS. PMID:27195197

  2. A one-dimensional model of PCP signaling: polarized cell behavior in the notochord of the ascidian Ciona

    PubMed Central

    Kourakis, Matthew J.; Reeves, Wendy; Newman-Smith, Erin; Maury, Benoit; Abdul-Wajid, Sarah; Smith, William C.

    2014-01-01

    Despite its importance in development and physiology the planar cell polarity (PCP) pathway remains one of the most enigmatic signaling mechanisms. The notochord of the ascidian Ciona provides a unique model for investigating the PCP pathway. Interestingly, the notochord appears to be the only embryonic structure in Ciona activating the PCP pathway. Moreover, the Ciona notochord as a single-file array of forty polarized cells is a uniquely tractable system for the study of polarization dynamics and the transmission of the PCP pathway. Here, we test models for propagation of a polarizing signal, interrogating temporal, spatial and signaling requirements. A simple cell-cell relay cascading through the entire length of the notochord is not supported; instead a more complex mechanism is revealed, with interactions influencing polarity between neighboring cells, but not distant ones. Mechanisms coordinating notochord-wide polarity remain elusive, but appear to entrain general (i.e., global) polarity even while local interactions remain important. However, this global polarizer does not appear to act as a localized, spatially-restricted determinant. Coordination of polarity along the long axis of the notochord requires the PCP pathway, a role we demonstrate is temporally distinct from this pathway’s earlier role in convergent extension and intercalation. We also reveal polarity in the notochord to be dynamic: a cell’s polarity state can be changed and then restored, underscoring the Ciona notochord’s amenability for in vivo studies of PCP. PMID:25173874

  3. 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) ...

  4. 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) ...

  5. The early origin of vertebral anomalies, as illustrated by a 'butterfly vertebra'.

    PubMed Central

    Müller, F; O'Rahilly, R; Benson, D R

    1986-01-01

    An anomalous (butterfly) eleventh thoracic vertebra in a fetus of 63 mm greatest length is described and graphic reconstructions (together with normal controls) are provided. The cartilaginous hemicentra are separated by disc-like material. Cartilaginous bars to adjacent vertebrae are present. The neural arch is complete. The notochord is not duplicated. Only one comparable case in the embryonic period has been described previously. After a discussion of cleft vertebrae in the human and in experimental animals, a developmental timetable of the appearance of several vertebral anomalies is provided. The sensitive period for butterfly vertebrae, depending on the mode of origin, seems to be 3-6 postovulatory weeks. More severe anomalies, such as the split notochord syndrome, appear earlier. It is concluded that most of the vertebral anomalies discussed arise during the embryonic period proper, although the timing of a few, such as spina bifida occulta, extends into the early fetal period. Images Fig. 1 Fig. 3 Fig. 5 PMID:3693103

  6. The origin of the vertebrate skeleton

    NASA Astrophysics Data System (ADS)

    Pivar, Stuart

    2011-01-01

    The anatomy of the human and other vertebrates has been well described since the days of Leonardo da Vinci and Vesalius. The causative origin of the configuration of the bones and of their shapes and forms has been addressed over the ensuing centuries by such outstanding investigators as Goethe, Von Baer, Gegenbauer, Wilhelm His and D'Arcy Thompson, who sought to apply mechanical principles to morphogenesis. However, no coherent causative model of morphogenesis has ever been presented. This paper presents a causative model for the origin of the vertebrate skeleton, based on the premise that the body is a mosaic enlargement of self-organized patterns engrained in the membrane of the egg cell. Drawings illustrate the proposed hypothetical origin of membrane patterning and the changes in the hydrostatic equilibrium of the cytoplasm that cause topographical deformations resulting in the vertebrate body form.

  7. 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.

  8. Late Development of Hagfish Vertebral Elements

    PubMed Central

    Ota, Kinya G; Fujimoto, Satoko; Oisi, Yasuhiro; Kuratani, Shigeru

    2013-01-01

    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. J. Exp. Zool. (Mol. Dev. Evol.) 320B:129–139, 2013. © 2013 Wiley Periodicals, Inc. PMID:23401412

  9. Differential gene expression in notochord and nerve cord fate segregation in the Ciona intestinalis embryo.

    PubMed

    Kobayashi, Kenji; Yamada, Lixy; Satou, Yutaka; Satoh, Nori

    2013-09-01

    During early embryogenesis, embryonic cells gradually restrict their developmental potential and are eventually destined to give rise to one type of cells. Molecular mechanisms underlying developmental fate restriction are one of the major research subjects within developmental biology. In this article, this subject was addressed by combining blastomere isolation with microarray analysis. During the 6th cleavage of the Ciona intestinalis embryo, from the 32-cell to the 64-cell stage, four mother cells divide into daughter cells with two distinct fates, one giving rise to notochord precursor cells and the other to nerve cord precursors. Approximately 2,200 each of notochord and nerve cord precursor cells were isolated, and their mRNA expression profiles were compared by microarray. This analysis identified 106 and 68 genes, respectively, that are differentially expressed in notochord and nerve cord precursor cells. These included not only genes for transcription factors and signaling molecules but also those with generalized functions observed in many types of cells. In addition, whole-mount in situ hybridization showed dynamic spatial expression profiles of these genes during segregation of the two fates: partitioning of transcripts present in the mother cells into either type of daughter cells, and initiation of preferential gene expression in either type of cells.

  10. 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

  11. 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.

  12. New insights into the complex structure and ontogeny of the occipito-vertebral gap in barbeled dragonfishes (Stomiidae, Teleostei).

    PubMed

    Schnell, Nalani K; Britz, Ralf; Johnson, G David

    2010-08-01

    In all stomiid genera there is an occipito-vertebral gap between the skull and the first vertebra bridged only by the flexible notochord. Morphological studies from the early 20th century suggested that some stomiid genera have 1-10 of the anteriormost centra reduced or entire vertebrae missing in this region. Our study reviews this previous hypothesis. Using a new approach, we show that only in Chauliodus, Eustomias and Leptostomias gladiator vertebral centra are actually lost, with their respective neural arches and parapophyses persisting. We present results from a comparative analysis of the number and insertion sites of the anteriormost myosepta in 26 of the 28 stomiid genera. Generally in teleosts the first three myosepta are associated with the occiput, and the fourth is the first vertebral myoseptum. The insertion site of the fourth myoseptum plays an important role in this analysis, because it provides a landmark for the first vertebra. Lack of association of the fourth myoseptum with a vertebra is thus evidence that the first vertebra is reduced or absent. By counting the occipital and vertebral myosepta the number of reduced vertebrae in Chauliodus, Eustomias and Leptostomias gladiator can be inferred. Proper identification of the spino-occipital nerves provides an additional source of information about vertebral reduction. In all other stomiid genera the extensive occipito- vertebral gap is not a consequence of the reduction of vertebrae, but of an elongation of the notochord. The complex structure and ontogeny of the anterior part of the vertebral column of stomiids are discussed comparatively.

  13. Cellular Morphogenesis In Silico

    PubMed Central

    Shinbrot, Troy; Chun, Young; Caicedo-Carvajal, Carlos; Foty, Ramsey

    2009-01-01

    Abstract We describe a model that simulates spherical cells of different types that can migrate and interact either attractively or repulsively. We find that both expected morphologies and previously unreported patterns spontaneously self-assemble. Among the newly discovered patterns are a segmented state of alternating discs, and a “shish-kebab” state, in which one cell type forms a ring around a second type. We show that these unique states result from cellular attraction that increases with distance (e.g., as membranes stretch viscoelastically), and would not be seen in traditional, e.g., molecular, potentials that diminish with distance. Most of the states found computationally have been observed in vitro, and it remains to be established what role these self-assembled states may play in in vivo morphogenesis. PMID:19686642

  14. On Buckling Morphogenesis.

    PubMed

    Nelson, Celeste M

    2016-02-01

    Cell-generated mechanical forces drive many of the tissue movements and rearrangements that are required to transform simple populations of cells into the complex three-dimensional geometries of mature organs. However, mechanical forces do not need to arise from active cellular movements. Recent studies have illuminated the roles of passive forces that result from mechanical instabilities between epithelial tissues and their surroundings. These mechanical instabilities cause essentially one-dimensional epithelial tubes and two-dimensional epithelial sheets to buckle or wrinkle into complex topologies containing loops, folds, and undulations in organs as diverse as the brain, the intestine, and the lung. Here, I highlight examples of buckling and wrinkling morphogenesis, and suggest that this morphogenetic mechanism may be broadly responsible for sculpting organ form.

  15. On Buckling Morphogenesis

    PubMed Central

    Nelson, Celeste M.

    2016-01-01

    Cell-generated mechanical forces drive many of the tissue movements and rearrangements that are required to transform simple populations of cells into the complex three-dimensional geometries of mature organs. However, mechanical forces do not need to arise from active cellular movements. Recent studies have illuminated the roles of passive forces that result from mechanical instabilities between epithelial tissues and their surroundings. These mechanical instabilities cause essentially one-dimensional epithelial tubes and two-dimensional epithelial sheets to buckle or wrinkle into complex topologies containing loops, folds, and undulations in organs as diverse as the brain, the intestine, and the lung. Here, I highlight examples of buckling and wrinkling morphogenesis, and suggest that this morphogenetic mechanism may be broadly responsible for sculpting organ form. PMID:26632268

  16. Physics of bacterial morphogenesis.

    PubMed

    Sun, Sean X; Jiang, Hongyuan

    2011-12-01

    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.

  17. 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

  18. Notochord-derived hedgehog is essential for tail regeneration in Xenopus tadpole

    PubMed Central

    2014-01-01

    Background Appendage regeneration in amphibians is regulated by the combinatorial actions of signaling molecules. The requirement of molecules secreted from specific tissues is reflected by the observation that the whole process of regeneration can be inhibited if a certain tissue is removed from the amputated stump. Interestingly, urodeles and anurans show different tissue dependencies during tail regeneration. The spinal cord is essential for tail regeneration in urodele but not in anuran larva, whereas the notochord but not the spinal cord is essential for tail regeneration in anuran tadpoles. Sonic hedgehog is one of the signaling molecules responsible for such phenomenon in axolotl, as hedgehog signaling is essential for overall tail regeneration and sonic hedgehog is exclusively expressed in the spinal cord. In order to know whether hedgehog signaling is involved in the molecular mechanism underlying the inconsistent tissue dependency for tail regeneration between anurans and urodeles, we investigated expression of hedgehog signal-related genes in the regenerating tail of Xenopus tadpole and examined the effect of the hedgehog signal inhibitor, cyclopamine, on the tail regeneration. Results In Xenopus, sonic hedgehog is expressed exclusively in the notochord but not in the spinal cord of the regenerate. Overall regeneration was severely impaired in cyclopamine-treated tadpoles. Notochord maturation in the regenerate, including cell alignment and vacuolation, and myofiber formation were inhibited. Proliferation of spinal cord cells in the neural ampulla and of mesenchymal cells was also impaired. Conclusion As in the axolotl, hedgehog signaling is required for multiple steps in tail regeneration in the Xenopus tadpole, although the location of the Shh source is quite different between the two species. This difference in Shh localization is the likely basis for the differing tissue requirement for tail regeneration between urodeles and anurans. PMID:24941877

  19. Generation of knock-in mice that express nuclear enhanced green fluorescent protein and tamoxifen-inducible Cre recombinase in the notochord from Foxa2 and T loci.

    PubMed

    Imuta, Yu; Kiyonari, Hiroshi; Jang, Chuan-Wei; Behringer, Richard R; Sasaki, Hiroshi

    2013-03-01

    The node and the notochord are important embryonic signaling centers that control embryonic pattern formation. Notochord progenitor cells present in the node and later in the posterior end of the notochord move anteriorly to generate the notochord. To understand the dynamics of cell movement during notochord development and the molecular mechanisms controlling this event, analyses of cell movements using time-lapse imaging and conditional manipulation of gene activities are required. To achieve this goal, we generated two knock-in mouse lines that simultaneously express nuclear enhanced green fluorescent protein (EGFP) and tamoxifen-inducible Cre, CreER(T2) , from two notochord gene loci, Foxa2 and T (Brachury). In Foxa2(nEGFP-CreERT2/+) and T(nEGFP-CreERT2/+) embryos, nuclei of the Foxa2 or T-expressing cells, which include the node, notochord, and endoderm (Foxa2) or wide range of posterior mesoderm (T), were labeled with EGFP at intensities that can be used for live imaging. Cre activity was also induced in cells expressing Foxa2 and T 1 day after tamoxifen administration. These mice are expected to be useful tools for analyzing the mechanisms of notochord development.

  20. Whole Transcriptome Analysis of Notochord-Derived Cells during Embryonic Formation of the Nucleus Pulposus.

    PubMed

    Peck, Sun H; McKee, Kendra K; Tobias, John W; Malhotra, Neil R; Harfe, Brian D; Smith, Lachlan J

    2017-09-05

    Recapitulation of developmental signals represents a promising strategy for treating intervertebral disc degeneration. During development, embryonic notochord-derived cells (NDCs) are the direct progenitors of cells that populate the adult nucleus pulposus (NP) and are an important source of secreted signaling molecules. The objective of this study was to define global gene expression profiles of NDCs at key stages of embryonic disc formation. NDCs were isolated from Shh-cre;ROSA:YFP mice at embryonic day 12.5 and postnatal day 0, representing opposite ends of the notochord to NP transformation. Differences in global mRNA abundance across this developmental window were established using RNA-Seq. Protein expression of selected molecules was confirmed using immunohistochemistry. Principal component analysis revealed clustering of gene expression at each developmental stage with more than 5000 genes significantly differentially expressed between E12.5 and P0. There was significantly lower mRNA abundance of sonic hedgehog pathway elements at P0 vs E12.5, while abundance of elements of the transforming growth factor-beta and insulin-like growth factors pathways, and extracellular matrix components including collagen 6 and aggrecan, were significantly higher at P0. This study represents the first transcriptome-wide analysis of embryonic NDCs. Results suggest signaling and biosynthesis of NDCs change dramatically as a function of developmental stage.

  1. Sensitivity of notochordal disc cells to mechanical loading: an experimental animal study.

    PubMed

    Guehring, Thorsten; Nerlich, Andreas; Kroeber, Markus; Richter, Wiltrud; Omlor, Georg W

    2010-01-01

    The immature disc nucleus pulposus (NP) consists of notochordal cells (NCs). With maturation NCs disappear in humans, to be replaced by chondrocyte-like mature NP cells (MNPCs); this change in cell phenotype coincidences with early signs of disc degeneration. The reasons for NC disappearance are important to understand disc degeneration, but remain unknown, yet. This study investigated, whether loading induced a change from a notochordal nucleus phenotype to a chondrocyte-like one. An in vivo disc compression model with fixateur externe was used in 36 mature rabbits. Discs were compressed for different time periods (1, 28, 56 days), and compared with uncompressed control discs (56 days without treatment), and discs with sham compression (28 days). Nucleus cell phenotype was determined by histology and immunohistochemistry. NCs, but not MNPCs highly expressed bone-morphogenetic-protein 2 and cytokeratin 8, thus NC and MNPC numbers could be determined. A histologic score was used to detect structural endplate changes after compression (28 days). Control and sham compressed discs contained around 70% NCs and 30% MNPCs, to be decreased to <10% NCs after 28-56 days of loading. NC density fell sharply by >50% after 28-56 days of compression (P < 0.05 vs. controls). Signs of decreased endplate cellularity and increased endplate sclerosis and fibrosis were found after loading. These experiments show that NCs were less resistant to mechanical stress than MNPCs suggesting that increased intradiscal pressures after loading, and limited nutrition through structurally altered endplates could instigate the disappearance of NCs.

  2. Bioelectromagnetics in morphogenesis.

    PubMed

    Levin, Michael

    2003-07-01

    Understanding the factors that allow biological systems to reliably self-assemble consistent, highly complex, four dimensional patterns on many scales is crucial for the biomedicine of cancer, regeneration, and birth defects. The role of chemical signaling factors in controlling embryonic morphogenesis has been a central focus in modern developmental biology. While the role of tensile forces is also beginning to be appreciated, another major aspect of physics remains largely neglected by molecular embryology: electromagnetic fields and radiations. The continued progress of molecular approaches to understanding biological form and function in the post genome era now requires the merging of genetics with functional understanding of biophysics and physiology in vivo. The literature contains much data hinting at an important role for bioelectromagnetic phenomena as a mediator of morphogenetic information in many contexts relevant to embryonic development. This review attempts to highlight briefly some of the most promising (and often underappreciated) findings that are of high relevance for understanding the biophysical factors mediating morphogenetic signals in biological systems. These data originate from contexts including embryonic development, neoplasm, and regeneration.

  3. PATHWAYS OF CELLULAR MORPHOGENESIS

    PubMed Central

    Green, Paul B.

    1965-01-01

    Evidence is presented to show that a given change in cell form or size may generally be brought about by a variety of patterns of local surface distortion and expansion. Structural and chemical features of the cell which are important in morphogenesis may thus be expected to relate not to form per se but to the kinetics of surface behavior which establish form. These kinetics evaluate both the rate at which local regions of cell surface expand and the directed character (anisotropy) of this expansion. These variables have been studied in model systems and, through marking experiments, in growing cells of various shapes in Phycomyces, Clypeaster, and particularly Nitella. In the latter plant, prominent "giant internodes" display a well defined longitudinal anisotropic expansion devoid of sizeable gradients in expansion rate. These cells have their origin, however, in apical cells which have a pronounced gradient in area expansion rate (maximal at the tip). The great part of the expansion in the apical cell is apparently isotropic (equal in all directions), but the basal region often shows predominant expansion laterally. This transverse stretching in the apical cell could align cell wall texture and possibly fibrous cytoplasmic constituents, such as microtubules, into configurations significant in later morphogenetic stages, including the elongation of the internodes. PMID:5884630

  4. 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.

  5. Inhibition of "spontaneous," notochord-induced, and collagen-induced in vitro somite chondrogenesis by the calcium lonophore, A23187.

    PubMed

    Kosher, R A

    1978-02-01

    The present study represents a first step in investigating the possible involvement of calcium (Ca2+) in the stimulation of somite chondrogenesis elicited by extracellular matrix components produced by the embryonic notochord. The ionophore, A23187, a drug that facilitates Ca2+ uptake leading to elevation of cytoplasmic Ca2+ levels, at concentrations of 0.25-1.0 microgram/ml severely impairs "spontaneous" somite chondrogenesis, i.e., inhibits the formation of the small amount of cartilaginous matrix normally formed by embryonic somites in vitro in the absence of inducing tissues. This inhibition is reflected in a considerable reduction in sulfated glycosaminoglycan (GAG) accumulation by A23187-treated somite explants. Furthermore, A23187 inhibits the striking stimulation of cartilaginous matrix formation and sulfated GAG accumulation normally elicited by the embryonic notochord and collagen substrates. In fact, 1.0 microgram/ml of A23187 reduces sulfated GAG accumulation by somites cultured in association with notochord or on collagen to a level even below that accumulated by somites cultured in the absence of these inductive agents. Although these results must be interpreted with caution, they provide incentive for considering a possible regulatory role for Ca2+ in the chondrogenic response of somites to extracellular matrix components produced by the embryonic notochord.

  6. Hyaluronan in limb morphogenesis.

    PubMed

    Li, Yingcui; Toole, Bryan P; Dealy, Caroline N; Kosher, Robert A

    2007-05-15

    Hyaluronan (HA) is a large glycosaminoglycan that is not only a structural component of extracellular matrices, but also interacts with cell surface receptors to promote cell proliferation, migration, and intracellular signaling. HA is a major component of the extracellular matrix of the distal subapical mesenchymal cells of the developing limb bud that are undergoing proliferation, directed migration, and patterning in response to the apical ectodermal ridge (AER), and has the functional potential to be involved in these processes. Here we show that the HA synthase Has2 is abundantly expressed by the distal subridge mesodermal cells of the chick limb bud and also by the AER itself. Has2 expression and HA production are downregulated in the proximal central core of the limb bud during the formation of the precartilage condensations of the skeletal elements, suggesting that downregulation of HA may be necessary for the close juxtaposition of cells and the resulting cell-cell interactions that trigger cartilage differentiation during condensation. Overexpression of Has2 in the mesoderm of the chick limb bud in vivo results in the formation of shortened and severely malformed limbs that lack one or more skeletal elements. Skeletal elements that do form in limbs overexpressing Has2 are reduced in length, exhibit abnormal morphology, and are positioned inappropriately. We also demonstrate that sustained HA production in micromass cultures of limb mesenchymal cells inhibits formation of precartilage condensations and subsequent chondrogenesis, indicating that downregulation of HA is indeed necessary for formation of the precartilage condensations that trigger cartilage differentiation. Taken together these results suggest involvement of HA in various aspects of limb morphogenesis.

  7. 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.

  8. Lipid synthesis during morphogenesis of Mucor racemosus.

    PubMed Central

    Ito, E T; Cihlar, R L; Inderlied, C B

    1982-01-01

    Lipid synthesis increases coordinately with protein and RNA synthesis during morphogenesis of Mucor racemosus. The lipid synthesis inhibitor cerulenin can completely block morphogenesis under conditions in which cell growth continues. An increase in phospholipid turnover may be an important correlate to morphogenesis of Mucor spp., especially the turnover of phosphotidyl inositol and phosphatidyl ethanolamine. The increase in ornithine decarboxylase, which occurs during morphogenesis, is inhibited by the addition of cerulenin. Images PMID:7130131

  9. Direct activation of Shroom3 transcription by Pitx proteins drives epithelial morphogenesis in the developing gut

    PubMed Central

    Chung, Mei-I; Nascone-Yoder, Nanette M.; Grover, Stephanie A.; Drysdale, Thomas A.; Wallingford, John B.

    2010-01-01

    Individual cell shape changes are essential for epithelial morphogenesis. A transcriptional network for epithelial cell shape change is emerging in Drosophila, but this area remains largely unexplored in vertebrates. The distinction is important as so far, key downstream effectors of cell shape change in Drosophila appear not to be conserved. Rather, Shroom3 has emerged as a central effector of epithelial morphogenesis in vertebrates, driving both actin- and microtubule-based cell shape changes. To date, the morphogenetic role of Shroom3 has been explored only in the neural epithelium, so the broad expression of this gene raises two important questions: what are the requirements for Shroom3 in non-neural tissues and what factors control Shroom3 transcription? Here, we show in Xenopus that Shroom3 is essential for cell shape changes and morphogenesis in the developing vertebrate gut and that Shroom3 transcription in the gut requires the Pitx1 transcription factor. Moreover, we show that Pitx proteins directly activate Shroom3 transcription, and we identify Pitx-responsive regulatory elements in the genomic DNA upstream of Shroom3. Finally, we show that ectopic expression of Pitx proteins is sufficient to induce Shroom3-dependent cytoskeletal reorganization and epithelial cell shape change. These data demonstrate new breadth to the requirements for Shroom3 in morphogenesis, and they also provide a cell-biological basis for the role of Pitx transcription factors in morphogenesis. More generally, these results provide a foundation for deciphering the transcriptional network that underlies epithelial cell shape change in developing vertebrates. PMID:20332151

  10. Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora.

    PubMed

    Lagman, Carlito; Varshneya, Kunal; Sarmiento, J Manuel; Turtz, Alan R; Chitale, Rohan V

    2016-03-30

    Ecchordosis physaliphora (EP) is a benign notochordal remnant derived from ectopic nests found along the craniospinal axis. It typically presents asymptomatically and is diagnosed using classic radiologic features, particularly location, T1-hypointensity, T2-hyperintensity, and lack of enhancement following gadolinium (Gd) contrast administration. Distinguishing EP from its malignant counterpart, chordoma, is of paramount importance, given the aggressive nature of the latter. Advances in imaging and immunohistochemistry have aided in diagnosis to an extent but, to our knowledge, identification of the genetic fingerprint of EP has yet to take place. Further cytological analysis of these lesions in search of a genetic link is warranted. We propose here a set of diagnostic criteria based on features consistently cited in the literature. In this literature review, 23 case reports were identified and collated into a summary of symptomatic cases of ecchordosis physaliphora. An illustrative case report of two patients was also included.

  11. Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora

    PubMed Central

    Lagman, Carlito; Sarmiento, J. Manuel; Turtz, Alan R; Chitale, Rohan V

    2016-01-01

    Ecchordosis physaliphora (EP) is a benign notochordal remnant derived from ectopic nests found along the craniospinal axis. It typically presents asymptomatically and is diagnosed using classic radiologic features, particularly location, T1-hypointensity, T2-hyperintensity, and lack of enhancement following gadolinium (Gd) contrast administration. Distinguishing EP from its malignant counterpart, chordoma, is of paramount importance, given the aggressive nature of the latter. Advances in imaging and immunohistochemistry have aided in diagnosis to an extent but, to our knowledge, identification of the genetic fingerprint of EP has yet to take place. Further cytological analysis of these lesions in search of a genetic link is warranted. We propose here a set of diagnostic criteria based on features consistently cited in the literature. In this literature review, 23 case reports were identified and collated into a summary of symptomatic cases of ecchordosis physaliphora. An illustrative case report of two patients was also included.  PMID:27158576

  12. 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

  13. Sensitivity of notochordal disc cells to mechanical loading: an experimental animal study

    PubMed Central

    Guehring, Thorsten; Nerlich, Andreas; Kroeber, Markus; Richter, Wiltrud

    2009-01-01

    The immature disc nucleus pulposus (NP) consists of notochordal cells (NCs). With maturation NCs disappear in humans, to be replaced by chondrocyte-like mature NP cells (MNPCs); this change in cell phenotype coincidences with early signs of disc degeneration. The reasons for NC disappearance are important to understand disc degeneration, but remain unknown, yet. This study investigated, whether loading induced a change from a notochordal nucleus phenotype to a chondrocyte-like one. An in vivo disc compression model with fixateur externe was used in 36 mature rabbits. Discs were compressed for different time periods (1, 28, 56 days), and compared with uncompressed control discs (56 days without treatment), and discs with sham compression (28 days). Nucleus cell phenotype was determined by histology and immunohistochemistry. NCs, but not MNPCs highly expressed bone-morphogenetic-protein 2 and cytokeratin 8, thus NC and MNPC numbers could be determined. A histologic score was used to detect structural endplate changes after compression (28 days). Control and sham compressed discs contained around 70% NCs and 30% MNPCs, to be decreased to <10% NCs after 28–56 days of loading. NC density fell sharply by >50% after 28–56 days of compression (P < 0.05 vs. controls). Signs of decreased endplate cellularity and increased endplate sclerosis and fibrosis were found after loading. These experiments show that NCs were less resistant to mechanical stress than MNPCs suggesting that increased intradiscal pressures after loading, and limited nutrition through structurally altered endplates could instigate the disappearance of NCs. PMID:19936803

  14. Notochordal cell-derived conditioned medium protects human nucleus pulposus cells from stress-induced apoptosis.

    PubMed

    Mehrkens, Arne; Matta, Ajay; Karim, Muhammad Zia; Kim, Sarah; Fehlings, Michael G; Schaeren, Stefan; Mark Erwin, William

    2017-04-01

    Degenerative disc disease (DDD) remains without an effective therapy and presents a costly burden to society. Based upon prior reports concerning the effects of notochordal cell-conditioned medium (NCCM) on disc cells, we performed a proof of principle study to determine whether NCCM could reduce cytotoxic stress-induced apoptosis in human disc nucleus pulposus (NP) cells. This is an "in vitro" fundamental or basic science study. Nucleus pulpous cells derived from 15 patients undergoing spinal surgery were treated with interleukin (IL)-1β and Fas ligand or etoposide in the presence of NCCM. We determined pro- or antiapoptotic events using activated caspase assays and determined genomic regulation of apoptosis using polymerase chain reaction arrays validated using Western blotting methods. We interrogated cellular apoptotic regulation using JC-1 dye and flow cytometry and performed enzyme-linked immunosorbent assays to evaluate NP inflammatory cytokine secretion. Notochordal cell-conditioned medium inhibits cytotoxic stress-induced caspase-9 and -3/7 activities and maintains the mitochondrial membrane potential in human NP cells, thereby suppressing the intrinsic apoptotic pathway. Gene expression analysis revealed the X-linked inhibitor of apoptosis protein as a key player responsible for evading etoposide-induced apoptosis in the presence of NCCM, and we verified these data using Western blotting. Enzyme-linked immunosorbent assay results revealed distinct differences in IL-6 and IL-8 secretions by NP cells in response to etoposide in the presence of NCCM. Here we demonstrate for the first time that NCCM reduces cytotoxic stress-induced apoptosis in human NP cells. Soluble factors present in NCCM could be harnessed for the development of novel therapeutics for the treatment of DDD. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Vertebrate skeletogenesis

    PubMed Central

    Lefebvre, Véronique; Bhattaram, Pallavi

    2011-01-01

    Vertebrate skeletogenesis consists in elaborating an edifice of more than 200 pieces of bone and cartilage. Each skeletal piece is crafted at a distinct location in the body, is articulated with others, and reaches a specific size, shape, and tissue composition according to both species instructions and individual determinants. This complex, customized body frame fulfills multiple essential tasks. It confers morphological features, allows controlled postures and movements, protects vital organs, houses hematopoiesis, stores minerals, and adsorbs toxins. This review provides an overview of the multiple facets of this ingenious process for experts as well as non-experts of skeletogenesis. We explain how the developing vertebrate uses both specific and ubiquitously expressed genes to generate multipotent mesenchymal cells, specify them to a skeletogenic fate, control their survival and proliferation, and direct their differentiation into cartilage, bone and joint cells. We review milestone discoveries made towards uncovering the intricate networks of regulatory factors that are involved in these processes, with an emphasis on signaling pathways and transcription factors. We describe numerous skeletal malformation and degeneration diseases that occur in humans as a result of mutations in regulatory genes, and explain how these diseases both help and motivate us to further decipher skeletogenic processes. Upon discussing current knowledge and gaps in knowledge in the control of skeletogenesis, we highlight ultimate research goals, and propose research priorities and approaches for future endeavors. PMID:20691853

  16. Mechanotransduction: getting morphogenesis down pat.

    PubMed

    Hardin, Jeff

    2011-05-10

    Embryonic morphogenesis requires the coordination of forces across multiple tissues and their associated extracellular matrices. A new study reports a mechanical feedback loop in the Caenorhabditis elegans embryo between muscle and epidermis that may provide a model for understanding how tissues coordinate morphogenetic events in the embryo.

  17. Chemotactic collapse and mesenchymal morphogenesis

    NASA Astrophysics Data System (ADS)

    Escudero, Carlos

    2005-08-01

    We study the effect of chemotactic signaling among mesenchymal cells. We show that the particular physiology of the mesenchymal cells allows one-dimensional collapse in contrast to the case of bacteria, and that the mesenchymal morphogenesis represents thus a more complex type of pattern formation than those found in bacterial colonies. We compare our theoretical predictions with recent in vitro experiments.

  18. Cellular Mechanisms of Drosophila Heart Morphogenesis

    PubMed Central

    Vogler, Georg; Bodmer, Rolf

    2015-01-01

    Many of the major discoveries in the fields of genetics and developmental biology have been made using the fruit fly, Drosophila melanogaster. With regard to heart development, the conserved network of core cardiac transcription factors that underlies cardiogenesis has been studied in great detail in the fly, and the importance of several signaling pathways that regulate heart morphogenesis, such as Slit/Robo, was first shown in the fly model. Recent technological advances have led to a large increase in the genomic data available from patients with congenital heart disease (CHD). This has highlighted a number of candidate genes and gene networks that are potentially involved in CHD. To validate genes and genetic interactions among candidate CHD-causing alleles and to better understand heart formation in general are major tasks. The specific limitations of the various cardiac model systems currently employed (mammalian and fish models) provide a niche for the fly model, despite its evolutionary distance to vertebrates and humans. Here, we review recent advances made using the Drosophila embryo that identify factors relevant for heart formation. These underline how this model organism still is invaluable for a better understanding of CHD. PMID:26236710

  19. Ontogeny of the vertebral column of Eleutherodactylus johnstonei (Anura: Eleutherodactylidae) reveals heterochronies relative to metamorphic frogs.

    PubMed

    Meza-Joya, Fabio Leonardo; Ramos-Pallares, Eliana Patricia; Ramírez-Pinilla, Martha Patricia

    2013-07-01

    Over the last century, the morphogenesis of the vertebral column has been considered as a highly conserved process among anurans. This statement is based on the study of few metamorphic taxa, ignoring the role of developmental mechanisms underlying the evolution of specialized life-histories. Direct development in anurans has been regarded as evolutionarily derived and involves developmental recapitulation and repatterning at different levels in all amphibian taxa studied so far. Herein, we analyze the vertebral column morphogenesis of the direct-developing frog Eleutherodactylus johnstonei, describing the sequence of chondrification and ossification, based on cleared and double-stained specimens from early stage embryos to adults. In general, our results show that the morphogenesis of the vertebral column in E. johnstonei recapitulates the ancestral tadpole-like pattern of development. However, the analysis of the sequence of events using heterochrony plots shows important heterocronies relative to metamorphic species, such as a delay in the chondrification of the vertebral centra and in osteogenesis. These ontogenetic peculiarities may represent derived traits in direct-developing frogs and are possibly correlated with its unusual life history. In addition, several features of the vertebral column of E. johnstonei are highly variable from its typical morphology. We report some malformations and small deviations, which do not seem to affect the survival of individuals. These anomalies have also been found in other frogs, and include many vertebral defects, such as vertebral fusion, and vertebral preclusion and/or induction.

  20. Analysis of cellular behavior and cytoskeletal dynamics reveal a constriction mechanism driving optic cup morphogenesis.

    PubMed

    Nicolás-Pérez, María; Kuchling, Franz; Letelier, Joaquín; Polvillo, Rocío; Wittbrodt, Jochen; Martínez-Morales, Juan R

    2016-10-31

    Contractile actomyosin networks have been shown to power tissue morphogenesis. Although the basic cellular machinery generating mechanical tension appears largely conserved, tensions propagate in unique ways within each tissue. Here we use the vertebrate eye as a paradigm to investigate how tensions are generated and transmitted during the folding of a neuroepithelial layer. We record membrane pulsatile behavior and actomyosin dynamics during zebrafish optic cup morphogenesis by live imaging. We show that retinal neuroblasts undergo fast oscillations and that myosin condensation correlates with episodic contractions that progressively reduce basal feet area. Interference with lamc1 function impairs basal contractility and optic cup folding. Mapping of tensile forces by laser cutting uncover a developmental window in which local ablations trigger the displacement of the entire tissue. Our work shows that optic cup morphogenesis is driven by a constriction mechanism and indicates that supra-cellular transmission of mechanical tension depends on ECM attachment.

  1. Vertebrate-like regeneration in the invertebrate chordate amphioxus

    PubMed Central

    Somorjai, Ildikó M. L.; Garcia-Fernàndez, Jordi; Escrivà, Hector

    2012-01-01

    An important question in biology is why some animals are able to regenerate, whereas others are not. The basal chordate amphioxus is uniquely positioned to address the evolution of regeneration. We report here the high regeneration potential of the European amphioxus Branchiostoma lanceolatum. Adults regenerate both anterior and posterior structures, including neural tube, notochord, fin, and muscle. Development of a classifier based on tail regeneration profiles predicts the assignment of young and old adults to their own class with >94% accuracy. The process involves loss of differentiated characteristics, formation of an msx-expressing blastema, and neurogenesis. Moreover, regeneration is linked to the activation of satellite-like Pax3/7 progenitor cells, the extent of which declines with size and age. Our results provide a framework for understanding the evolution and diversity of regeneration mechanisms in vertebrates. PMID:22203957

  2. Vertebrate Endoderm Development and Organ Formation

    PubMed Central

    Zorn, Aaron M.; Wells, James M.

    2010-01-01

    The endoderm germ layer contributes to the respiratory and gastrointestinal tracts, and all of their associated organs. Over the past decade, studies in vertebrate model organisms; including frog, fish, chick, and mouse; have greatly enhanced our understanding of the molecular basis of endoderm organ development. We review this progress with a focus on early stages of endoderm organogenesis including endoderm formation, gut tube morphogenesis and patterning, and organ specification. Lastly, we discuss how developmental mechanisms that regulate endoderm organogenesis are used to direct differentiation of embryonic stem cells into specific adult cell types, which function to alleviate disease symptoms in animal models. PMID:19575677

  3. Redundant roles of Tead1 and Tead2 in notochord development and the regulation of cell proliferation and survival.

    PubMed

    Sawada, Atsushi; Kiyonari, Hiroshi; Ukita, Kanako; Nishioka, Noriyuki; Imuta, Yu; Sasaki, Hiroshi

    2008-05-01

    Four members of the TEAD/TEF family of transcription factors are expressed widely in mouse embryos and adult tissues. Although in vitro studies have suggested various roles for TEAD proteins, their in vivo functions remain poorly understood. Here we examined the role of Tead genes by generating mouse mutants for Tead1 and Tead2. Tead2(-/-) mice appeared normal, but Tead1(-/-); Tead2(-/-) embryos died at embryonic day 9.5 (E9.5) with severe growth defects and morphological abnormalities. At E8.5, Tead1(-/-); Tead2(-/-) embryos were already small and lacked characteristic structures such as a closed neural tube, a notochord, and somites. Despite these overt abnormalities, differentiation and patterning of the neural plate and endoderm were relatively normal. In contrast, the paraxial mesoderm and lateral plate mesoderm were displaced laterally, and a differentiated notochord was not maintained. These abnormalities and defects in yolk sac vasculature organization resemble those of mutants for Yap, which encodes a coactivator of TEAD proteins. Moreover, we demonstrated genetic interactions between Tead1 and Tead2 and Yap. Finally, Tead1(-/-); Tead2(-/-) embryos showed reduced cell proliferation and increased apoptosis. These results suggest that Tead1 and Tead2 are functionally redundant, use YAP as a major coactivator, and support notochord maintenance as well as cell proliferation and survival in mouse development.

  4. Redundant Roles of Tead1 and Tead2 in Notochord Development and the Regulation of Cell Proliferation and Survival▿

    PubMed Central

    Sawada, Atsushi; Kiyonari, Hiroshi; Ukita, Kanako; Nishioka, Noriyuki; Imuta, Yu; Sasaki, Hiroshi

    2008-01-01

    Four members of the TEAD/TEF family of transcription factors are expressed widely in mouse embryos and adult tissues. Although in vitro studies have suggested various roles for TEAD proteins, their in vivo functions remain poorly understood. Here we examined the role of Tead genes by generating mouse mutants for Tead1 and Tead2. Tead2−/− mice appeared normal, but Tead1−/−; Tead2−/− embryos died at embryonic day 9.5 (E9.5) with severe growth defects and morphological abnormalities. At E8.5, Tead1−/−; Tead2−/− embryos were already small and lacked characteristic structures such as a closed neural tube, a notochord, and somites. Despite these overt abnormalities, differentiation and patterning of the neural plate and endoderm were relatively normal. In contrast, the paraxial mesoderm and lateral plate mesoderm were displaced laterally, and a differentiated notochord was not maintained. These abnormalities and defects in yolk sac vasculature organization resemble those of mutants for Yap, which encodes a coactivator of TEAD proteins. Moreover, we demonstrated genetic interactions between Tead1 and Tead2 and Yap. Finally, Tead1−/−; Tead2−/− embryos showed reduced cell proliferation and increased apoptosis. These results suggest that Tead1 and Tead2 are functionally redundant, use YAP as a major coactivator, and support notochord maintenance as well as cell proliferation and survival in mouse development. PMID:18332127

  5. 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.

  6. Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model

    PubMed Central

    2014-01-01

    Introduction The intervertebral disc has a complex structure originating developmentally from both the mesenchyme and notochord. Notochordal cells disappear during adolescence, which is also when human discs begin to show degenerative signs. During degeneration later in life, disc cells decline because of apoptosis. Although many animal models have been developed to simulate human disc degeneration, few studies have explored the long-term changes in cell population and phenotype. Our objective was to elucidate the time-dependent notochordal cell disappearance and apoptotic cell death in a rat tail static compression-induced disc degeneration model. Methods Twenty-four 12-week-old male Sprague–Dawley rat tails were instrumented with an Ilizarov-type device and loaded statically at 1.3 MPa for up to 56 days. Loaded and distal-unloaded discs were harvested. Changes in cell number and phenotype were assessed with histomorphology and immunofluorescence. Apoptosis involvement was determined with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry. Results The number of disc nucleus pulposus and annulus fibrosus cells decreased with the loading period; particularly, the decrease was notable at day 7 in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, indicating notochordal origin. Subsequently, the proportion of cells positive for TUNEL and cleaved caspase-3, markers of apoptosis induction, increased from day 7 through day 56. Although the percentage of cells immunopositive for cleaved caspase-8, a marker of apoptosis initiation through the death-receptor pathway, increased only at day 7, the percentage of cells immunopositive for cleaved caspase-9 and p53-regulated apoptosis-inducing protein 1 (p53AIP1), markers of apoptosis initiation through the p53-mediated mitochondrial pathway, increased from day 7 through day 56. The percentage of cells immunopositive for B-cell lymphoma 2 (Bcl-2) and silent

  7. Vertebral column and associated elements in dipnoans and comparison with other fishes: development and homology.

    PubMed

    Arratia, G; Schultze, H P; Casciotta, J

    2001-11-01

    A vertebral column consisting of a persistent notochord and ossified arcocentra is the primitive condition for Gnathostomata; it still persists in primitive actinopterygians and sarcopterygians. Advanced actinopterygians and sarcopterygians develop numerous types of centra that include, among others, the presence of holocentrum, chordacentrum, and autocentrum. The chordacentrum, a mineralization or calcification of the fibrous sheath of the notochord, is only found in actinopterygians, whereas an autocentrum is a synapomorphy of teleosts above Leptolepis coryphaenoides. The chordacentrum, formed by migration of cartilaginous cells from the arches into the fibrous sheath of the notochord and usually covered by a thin calcification, is a unique feature of chondrichthyans. The actinopterygian chordacentrum and the chondrichthyan chordacentrum are not homologous. The postcaudal cartilaginous centrum is only known in postcaudal vertebrae of living dipnoans. The holocentrum is present in certain fossil dipnoans and actinopterygians, where it has been independently acquired. It is formed by proliferation of cartilage cells around the elastica externa of the notochord. These cells later ossify, forming a compact centrum. A vertebral column formed by a persistent notochord without vertebral centra is the primitive pattern for all vertebrates. The formation of centra, which is not homologous among vertebrate groups, is acquired independently in some lineages of placoderms, most advanced actinopterygians, and some dipnoans and rhipidistians. Several series of structures are associated with the vertebral column such as the supraneurals, interhaemals, radials, and ribs. In living dipnoans median neural spine, "supraneural," and dorsal radial result from growth and distal differentiation of one median cartilage into two or three median bones during ontogeny. The median neural spine articulates with the neural arch and fuses with it in the caudal vertebrae early in ontogeny. Two

  8. Transcriptome analysis of vertebral bone in the flounder, Paralichthys olivaceus (Teleostei, Pleuronectiformes), using Illumina sequencing.

    PubMed

    Ibaraki, Harumi; Wu, Xiaoming; Uji, Susumu; Yokoi, Hayato; Sakai, Yoshifumi; Suzuki, Tohru

    2015-12-01

    The processes underlying vertebral development in teleosts and tetrapods differ markedly in a variety of ways. At present, the molecular basis of teleost vertebral development and growth is poorly understood. Understanding vertebral development at the molecular level is important for aquaculture to prevent vertebral anomalies that can arise from a variety of factors, including excess vitamin A (all-trans retinol, VA) in the diet. To facilitate studies on teloest vertebral development, we performed transcriptome analysis of four month old flounder, Paralichthys olivaceus, vertebrae using next-generation sequencing. Expression profile obtained demonstrates that some members of the hh, bmp, fgf, wnt gene families, and their receptors, hox, pax, sox, dlx and tbx gene families and ntl, which are known to function in notochord and somite development in embryos, are expressed in the vertebrae. It was also showed that in addition to the retinoic acid receptor (Rar), the vertebrae express alcohol dehydrogenase 1 and retinal dehydrogenase 2 which convert VA to all-trans-retinoic acid (RA). The assembled contigs also included cytochrome p450 family members, which inactivate RA, as well as phosphatidylcholine-retinol O-acetyltransferase, which converts VA to all-trans-retinyl ester, a stock form of VA. These data suggest that in teleost vertebrae, expression of various signals and transcription factors which function in the notochord and somite development is maintained until adult stage, and RA metabolism and signaling are active to regulate transcription of RA-responsible genes, such as hedgehog and hox genes. This is the first transcriptome analysis of teleost fish vertebrae.

  9. Morphogenesis and regionalization of the medaka embryonic brain.

    PubMed

    Kage, Takahiro; Takeda, Hiroyuki; Yasuda, Takako; Maruyama, Kouichi; Yamamoto, Naoyuki; Yoshimoto, Masami; Araki, Kazuo; Inohaya, Keiji; Okamoto, Hiroyuki; Yasumasu, Shigeki; Watanabe, Kaori; Ito, Hironobu; Ishikawa, Yuji

    2004-08-23

    We examined the morphogenesis and regionalization of the embryonic brain of an acanthopterygian teleost, medaka (Oryzias latipes), by in situ hybridization using 14 gene probes. We compared our results with previous studies in other vertebrates, particularly zebrafish, an ostariophysan teleost. During the early development of the medaka neural rod, three initial brain vesicles arose: the anterior brain vesicle, which later developed into the telencephalon and rostral diencephalon; the intermediate brain vesicle, which later developed into the caudal diencephalon, mesencephalon, and metencephalon; and the posterior brain vesicle, which later developed into the myelencephalon. In the late neural rod, the rostral brain bent ventrally and the axis of the brain had a marked curvature at the diencephalon. In the final stage of the neural rod, ventricles began to develop, transforming the neural rod into the neural tube. In situ hybridization revealed that the brain can be divided into three longitudinal zones (dorsal, intermediate, and ventral) and many transverse subdivisions, on the basis of molecular expression patterns. The telencephalon was subdivided into two transverse domains. Our results support the basic concept of neuromeric models, including the prosomeric model, which suggests the existence of a conserved organization of all vertebrate neural tubes. Our results also show that brain development in medaka differs from that reported in other vertebrates, including zebrafish, in gene-expression patterns in the telencephalon, in brain vesicle formation, and in developmental speed. Developmental and genetic programs for brain development may be somewhat different even among teleosts.

  10. Molecular mechanisms of dendrite morphogenesis

    PubMed Central

    Arikkath, Jyothi

    2012-01-01

    Dendrites are key integrators of synaptic information in neurons and play vital roles in neuronal plasticity. Hence, it is necessary that dendrite arborization is precisely controlled and coordinated with synaptic activity to ensure appropriate functional neural network integrity. In the past several years, it has become increasingly clear that several cell intrinsic and extrinsic mechanisms contribute to dendritic arborization. In this review, we will discuss some of the molecular mechanisms that regulate dendrite morphogenesis, particularly in cortical and hippocampal pyramidal neurons and some of the implications of aberrant dendritic morphology for human disease. Finally, we will discuss the current challenges and future directions in the field. PMID:23293584

  11. The role of retinoic acid in the morphogenesis of the neural tube

    PubMed Central

    Wilson, L; Gale, E; Maden, M

    2003-01-01

    We have examined the role of the signalling molecule, retinoic acid, in the process of neurulation and the subsequent growth and differentiation of the central nervous system using quail embryos that have developed in the absence of retinoic acid. Such retinoic acid-free embryos undergo abnormal neural tube formation in terms of its shape and structure, but the embryos do not display spina bifida or exencephaly. The neural tubes have a wider floor plate, a thicker roof plate and a different dorsoventral shape. Phalloidin staining and electron microscopy revealed alterations in the actin filaments and the junctional complexes of the cell layer lining the lumen. Initially the neural tubes proliferated at the same rate as normal, but later the proliferation rate declined drastically and neuronal differentiation was highly deficient. There were very few motoneurons extending neurites into the periphery, and within the neural tube axon trajectories were chaotic. These results reveal several functions for retinoic acid in the morphogenesis and growth of the neural tube, many of which can be explained by defective notochord signalling, but they do not suggest that this molecule plays a role in neural tube closure. PMID:14620376

  12. Eye morphogenesis and patterning of the optic vesicle.

    PubMed

    Fuhrmann, Sabine

    2010-01-01

    Organogenesis of the eye is a multistep process that starts with the formation of optic vesicles followed by invagination of the distal domain of the vesicles and the overlying lens placode resulting in morphogenesis of the optic cup. The late optic vesicle becomes patterned into distinct ocular tissues: the neural retina, retinal pigment epithelium (RPE), and optic stalk. Multiple congenital eye disorders, including anophthalmia or microphthalmia, aniridia, coloboma, and retinal dysplasia, stem from disruptions in embryonic eye development. Thus, it is critical to understand the mechanisms that lead to initial specification and differentiation of ocular tissues. An accumulating number of studies demonstrate that a complex interplay between inductive signals provided by tissue-tissue interactions and cell-intrinsic factors is critical to ensuring proper specification of ocular tissues as well as maintenance of RPE cell fate. While several of the extrinsic and intrinsic determinants have been identified, we are just at the beginning in understanding how these signals are integrated. In addition, we know very little about the actual output of these interactions. In this chapter, we provide an update of the mechanisms controlling the early steps of eye development in vertebrates, with emphasis on optic vesicle evagination, specification of neural retina and RPE at the optic vesicle stage, the process of invagination during morphogenesis of the optic cup, and maintenance of the RPE cell fate.

  13. Notochordal cells protect nucleus pulposus cells from degradation and apoptosis: implications for the mechanisms of intervertebral disc degeneration

    PubMed Central

    2011-01-01

    Introduction The relative resistance of non-chondrodystrophic (NCD) canines to degenerative disc disease (DDD) may be due to a combination of anabolic and anti-catabolic factors secreted by notochordal cells within the intervertebral disc (IVD) nucleus pulposus (NP). Factors known to induce DDD include interleukin-1 beta (IL-1ß) and/or Fas-Ligand (Fas-L). Therefore we evaluated the ability of notochordal cell conditioned medium (NCCM) to protect NP cells from IL-1ß and IL-1ß +FasL-mediated cell death and degeneration. Methods We cultured bovine NP cells with IL-1ß or IL-1ß+FasL under hypoxic serum-free conditions (3.5% O2) and treated the cells with either serum-free NCCM or basal medium (Advanced DMEM/F-12). We used flow cytometry to evaluate cell death and real-time (RT-)PCR to determine the gene expression of aggrecan, collagen 2, and link protein, mediators of matrix degradation ADAMTS-4 and MMP3, the matrix protection molecule TIMP1, the cluster of differentiation (CD)44 receptor, the inflammatory cytokine IL-6 and Ank. We then determined the expression of specific apoptotic pathways in bovine NP cells by characterizing the expression of activated caspases-3, -8 and -9 in the presence of IL-1ß+FasL when cultured with NCCM, conditioned medium obtained using bovine NP cells (BCCM), and basal medium all supplemented with 2% FBS. Results NCCM inhibits bovine NP cell death and apoptosis via suppression of activated caspase-9 and caspase-3/7. Furthermore, NCCM protects NP cells from the degradative effects of IL-1ß and IL-1ß+Fas-L by up-regulating the expression of anabolic/matrix protective genes (aggrecan, collagen type 2, CD44, link protein and TIMP-1) and down-regulating matrix degrading genes such as MMP-3. Expression of ADAMTS-4, which encodes a protein for aggrecan remodeling, is increased. NCCM also protects against IL-1+FasL-mediated down-regulation of Ank expression. Furthermore, NP cells treated with NCCM in the presence of IL-1ß+Fas-L down

  14. Intact glycosaminoglycans from intervertebral disc-derived notochordal cell-conditioned media inhibit neurite growth while maintaining neuronal cell viability.

    PubMed

    Purmessur, Devina; Cornejo, Marisa C; Cho, Samuel K; Roughley, Peter J; Linhardt, Robert J; Hecht, Andrew C; Iatridis, James C

    2015-05-01

    Painful human intervertebral discs (IVDs) exhibit nerve growth deep into the IVD. Current treatments for discogenic back pain do not address the underlying mechanisms propagating pain and are often highly invasive or only offer temporary symptom relief. The notochord produces factors during development that pattern the spine and inhibit the growth of dorsal root ganglion (DRG) axons into the IVD. We hypothesize that notochordal cell (NC)-conditioned medium (NCCM) includes soluble factors capable of inhibiting neurite growth and may represent a future therapeutic target. To test if NCCM can inhibit neurite growth and determine if NC-derived glycosaminoglycans (GAGs) are necessary candidates for this inhibition. Human neuroblastoma (SH-SY5Y) cells and rat DRG cells were treated with NCCM in two-dimensional culture in vitro, and digestion and mechanistic studies determined if specific GAGs were responsible for inhibitory effects. Notochordal cell-conditioned medium was generated from porcine nucleus pulposus tissue that was cultured in Dulbecco's modified eagle's medium for 4 days. A dose study was performed using SH-SY5Y cells that were seeded in basal medium for 24 hours and neurite outgrowth and cell viability were assessed after treatment with basal media or NCCM (10% and 100%) for 48 hours. Glycosaminoglycans from NCCM were characterized using multiple digestions and liquid chromatography mass spectroscopy (LC-MS). Neurite growth was assessed on both SH-SY5Y and DRG cells after treatment with NCCM with and without GAG digestion. Notochordal cell-conditioned medium significantly inhibited the neurite outgrowth from SH-SY5Y cells compared with basal controls without dose or cytotoxic effects; % of neurite expressing cells were 39.0±2.9%, 27.3±3.6%, and 30.2±2.7% and mean neurite length was 60.3±3.5, 50.8±2.4, 53.2±3.7 μm for basal, 10% NCCM, and 100% NCCM, respectively. Digestions and LC-MS determined that chondroitin-6-sulfate was the major GAG chain in

  15. Localization of type II collagen, long form alpha 1(IX) collagen, and short form alpha 1(IX) collagen transcripts in the developing chick notochord and axial skeleton.

    PubMed

    Swiderski, R E; Solursh, M

    1992-06-01

    In this study we compare, by in situ hybridization, the spatial and temporal expression patterns of transcripts of avian type II collagen and the long and short forms of the (alpha 1) chain of type IX collagen during the development of the notochord and axial skeleton. We observed type II collagen and short form type IX collagen transcripts in the developing (stage 25-28) nonchondrogenic notochord. Conversely, long form type IX transcripts were not detectable in the notochord or perinotochordal sheath. Interestingly, all three transcripts colocalized in the developing chondrogenic vertebrae of the axial skeleton as well as in the chondrocranium and Meckel's cartilage. The expression of the short form of type IX collagen in these regions was more restricted than that of the long form. This report provides additional support for a complex regulatory pathway of cartilage marker gene expression in chondrogenic vs. nonchondrogenic tissues during avian embryogenesis.

  16. Spatiotemporal analysis of putative notochordal cell markers reveals CD24 and keratins 8, 18, and 19 as notochord‐specific markers during early human intervertebral disc development

    PubMed Central

    Rodrigues‐Pinto, Ricardo; Berry, Andrew; Piper‐Hanley, Karen; Hanley, Neil; Richardson, Stephen M.

    2016-01-01

    ABSTRACT In humans, the nucleus pulposus (NP) is composed of large vacuolated notochordal cells in the fetus but, soon after birth, becomes populated by smaller, chondrocyte‐like cells. Although animal studies indicate that notochord‐derived cells persist in the adult NP, the ontogeny of the adult human NP cell population is still unclear. As such, identification of unique notochordal markers is required. This study was conducted to determine the spatiotemporal expression of putative human notochordal markers to aid in the elucidation of the ontogeny of adult human NP cells. Human embryos and fetuses (3.5–18 weeks post‐conception (WPC)) were microdissected to isolate the spine anlagens (notochord and somites/sclerotome). Morphology of the developing IVD was assessed using hematoxylin and eosin. Expression of keratin (KRT) 8, KRT18, KRT19, CD24, GAL3, CD55, BASP1, CTGF, T, CD90, Tie2, and E‐cadherin was assessed using immunohistochemistry. KRT8, KRT18, KRT19 were uniquely expressed by notochordal cells at all spine levels at all stages studied; CD24 was expressed at all stages except 3.5 WPC. While GAL3, CD55, BASP1, CTGF, and T were expressed by notochordal cells at specific stages, they were also co‐expressed by sclerotomal cells. CD90, Tie2, and E‐cadherin expression was not detectable in developing human spine cells at any stage. This study has identified, for the first time, the consistent expression of KRT8, KRT18, KRT19, and CD24 as human notochord‐specific markers during early IVD development. Thus, we propose that these markers can be used to help ascertain the ontogeny of adult human NP cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 34:1327–1340, 2016. PMID:26910849

  17. Polarity in Mammalian Epithelial Morphogenesis

    PubMed Central

    Roignot, Julie; Peng, Xiao; Mostov, Keith

    2013-01-01

    Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture models has brought new insights into the mechanisms underlying the establishment and maintenance of higher-order epithelial tissue architecture, and in the dynamic remodeling of cell polarity that often occurs during development of epithelial organs. Here we discuss some important aspects of mammalian epithelial morphogenesis, from the establishment of cell polarity to epithelial tissue generation. PMID:23378592

  18. UV-B induced morphogenesis

    PubMed Central

    Jansen, Marcel A.K.; Coffey, Aoife M.; Prinsen, Els

    2012-01-01

    Low levels of ultraviolet (UV)-radiation alter the morphology of plants. UV-B exposure can lead to shorter petioles and shorter, narrower and/or thicker leaf blades. The resulting decrease in leaf area has been associated with inhibitory UV-B effects on biomass accumulation. In Arabidopsis, UV-B effects on leaf area have variously been attributed to altered cell division, cell expansion or combinations of these two processes. A dedicated UV-B sensory system, crosstalk between flavonoids and auxins, endoreduplication and generic Stress Induced Morphogenic Responses (SIMR) have all been proposed to contribute to the UV-B phenotype. Here, we propose that UV-mediated morphogenesis, rather than being controlled by a single regulatory pathway, is controlled by a regulatory blur involving multiple compensatory molecular and physiological feedback interactions. PMID:22899069

  19. 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...

  20. Increased osmolarity and cell clustering preserve canine notochordal cell phenotype in culture.

    PubMed

    Spillekom, Sandra; Smolders, Lucas A; Grinwis, Guy C M; Arkesteijn, Irene T M; Ito, Keita; Meij, Björn P; Tryfonidou, Marianna A

    2014-08-01

    Degeneration of the intervertebral disc (IVD) is associated with a loss of notochordal cells (NCs) from the nucleus pulposus (NP) and their replacement by chondrocyte-like cells. NCs are known to maintain extracellular matrix quality and stimulate the chondrocyte-like NP cells, making NCs attractive for designing new tissue engineering approaches for IVD regeneration. However, optimal conditions, such as osmolarity and other characteristics of the culture media, for long-term culture of NCs are not known. The purpose of this study was to investigate the effects of different culture media and osmolarity on the physiology of NCs in vitro. NC clusters isolated from canine IVDs were suspended in alginate beads and cultured at 37°C under normoxic conditions for 28 days. Three different culture conditions were investigated; (1) Dulbecco's modified Eagle's medium (DMEM)/F12 (300 mOsm/L), (2) α-MEM (300 mOsm/L), and (3) α-MEM adjusted to 400 mOsm/L to mimic a hyperosmolar environment. NC morphology, expression of genes related to NC markers, matrix production and remodeling, and DNA- and glycosaminoglycan (GAG) analyses were performed on 1, 7, 14, and 28 days in culture. Large, vesicle-containing cells organized in clusters, characterized as NCs, remained present during 28 days for all culture conditions. However, the proportion of the NC clusters decreased over time, whereas the proportion of spindle-shaped cells increased. Gene expression profiling at 7, 14, and 28 days in culture compared to day 1 indicated a initial loss of NC phenotype followed by some recovery of brachyury and aggrecan gene expression after 28 days of culture supporting a potential recovery of NC phenotype. NCs cultured in α-MEM adjusted to 400 mOsm/L showed the highest gene expression of brachyury, cytokeratin 18, and aggrecan, the highest GAG production, and the lowest collagen 1α1 gene expression. In conclusion, NCs cultured in alginate in native cell clusters, partially retained their

  1. Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus

    PubMed Central

    Matta, Ajay; Karim, M. Zia; Isenman, David E.; Erwin, W. Mark

    2017-01-01

    Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the non-chondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM). Ingenuity Pathway Analysis revealed TGFβ1 and CTGF as major hubs in protein interaction networks. In vitro treatment with TGFβ1 and CTGF promoted the synthesis of healthy extra-cellular matrix proteins, increased cell proliferation and reduced cell death in human degenerative disc NP cells. A single intra-discal injection of recombinant TGFβ1 and CTGF proteins in a pre-clinical rat-tail disc injury model restored the NC and stem cell rich NP. In conclusion, we demonstrate the potential of TGFβ1 and CTGF to mitigate the progression of disc degeneration and the potential use of these molecules in a molecular therapy to treat the degenerative disc. PMID:28358123

  2. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

  3. The three-dimensional architecture of the notochordal nucleus pulposus: novel observations on cell structures in the canine intervertebral disc.

    PubMed

    Hunter, Christopher J; Matyas, John R; Duncan, Neil A

    2003-03-01

    Cells from the nucleus pulposus of young (< 2 years) and old (> 5 years) non-chondrodystrophoid dogs were studied using routine histology, confocal laser scanning microscopy and transmission electron microscopy. The architecture of cell structures--from the tissue scale down to subcellular scale--was reported. Clusters of notochordal cells were observed in young nuclei pulposi, ranging from 10 to 426 cells each. These clusters resisted mechanical disruption and showed evidence of cell-cell signalling via gap junctions. Cells (30-40 microm in diameter) within the clusters had a physaliferous appearance, containing numerous large inclusions which ranged from 1 to 20 microm in diameter. The inclusions were surrounded by a dense actin cortex but were not contained by a lipid bilayer. The contents of the inclusions were determined not to be predominantly carbohydrate or neutral lipid as assessed by histochemical staining, but the exact composition of the contents remained uncertain. There were striking differences in the cell architecture of young vs. old nuclei pulposi, with a loss of both cell clusters and physaliferous cells during ageing. These observations demonstrate unique cell structures, which may influence our understanding of the differences between notochordal and chondrocytic cells in the nucleus pulposus. Such differences could have substantial impact upon how we think about development, degeneration and repair of the intervertebral disc.

  4. Hagfish and lancelet fibrillar collagens reveal that type II collagen-based cartilage evolved in stem vertebrates

    PubMed Central

    Zhang, GuangJun; Cohn, Martin J.

    2006-01-01

    The origin of vertebrates was defined by evolution of a skeleton; however, little is known about the developmental mechanisms responsible for this landmark evolutionary innovation. In jawed vertebrates, cartilage matrix consists predominantly of type II collagen (Col2α1), whereas that of jawless fishes has long been thought to be noncollagenous. We recently showed that Col2α1 is present in lamprey cartilage, indicating that type II collagen-based cartilage evolved earlier than previously recognized. Here, we investigate the origin of vertebrate cartilage, and we report that hagfishes, the sister group to lampreys, also have Col2α1-based cartilage, suggesting its presence in the common ancestor of crown-group vertebrates. We go on to show that lancelets, a sister group to vertebrates, possess an ancestral clade A fibrillar collagen (ColA) gene that is expressed in the notochord. Together, these results suggest that duplication and diversification of ColA genes at the chordate–vertebrate transition may underlie the evolutionary origin of vertebrate skeletal tissues. PMID:17077149

  5. Hagfish and lancelet fibrillar collagens reveal that type II collagen-based cartilage evolved in stem vertebrates.

    PubMed

    Zhang, Guangjun; Cohn, Martin J

    2006-11-07

    The origin of vertebrates was defined by evolution of a skeleton; however, little is known about the developmental mechanisms responsible for this landmark evolutionary innovation. In jawed vertebrates, cartilage matrix consists predominantly of type II collagen (Col2alpha1), whereas that of jawless fishes has long been thought to be noncollagenous. We recently showed that Col2alpha1 is present in lamprey cartilage, indicating that type II collagen-based cartilage evolved earlier than previously recognized. Here, we investigate the origin of vertebrate cartilage, and we report that hagfishes, the sister group to lampreys, also have Col2alpha1-based cartilage, suggesting its presence in the common ancestor of crown-group vertebrates. We go on to show that lancelets, a sister group to vertebrates, possess an ancestral clade A fibrillar collagen (ColA) gene that is expressed in the notochord. Together, these results suggest that duplication and diversification of ColA genes at the chordate-vertebrate transition may underlie the evolutionary origin of vertebrate skeletal tissues.

  6. Extracranial vertebral artery intervention.

    PubMed

    Mukherjee, Debabrata; Pineda, Guillermo

    2007-12-01

    Atherosclerosis is the commonest cause of vertebral artery stenosis and has a predilection for the origin and proximal section of the extracranial portion of the vessel and also the intracranial portion of the vessel. Although it has generally been thought that extracranial vertebral artery (ECVA) disease has a more benign outcome compared to intracranial vertebral artery disease, significant occlusive disease of the proximal vertebral artery is the primary cause of vertebral artery ischemia in a significant proportion of patients. We focus on the interventional management of patients with proximal ECVA disease in this article.

  7. Cell-intrinsic drivers of dendrite morphogenesis.

    PubMed

    Puram, Sidharth V; Bonni, Azad

    2013-12-01

    The proper formation and morphogenesis of dendrites is fundamental to the establishment of neural circuits in the brain. Following cell cycle exit and migration, neurons undergo organized stages of dendrite morphogenesis, which include dendritic arbor growth and elaboration followed by retraction and pruning. Although these developmental stages were characterized over a century ago, molecular regulators of dendrite morphogenesis have only recently been defined. In particular, studies in Drosophila and mammalian neurons have identified numerous cell-intrinsic drivers of dendrite morphogenesis that include transcriptional regulators, cytoskeletal and motor proteins, secretory and endocytic pathways, cell cycle-regulated ubiquitin ligases, and components of other signaling cascades. Here, we review cell-intrinsic drivers of dendrite patterning and discuss how the characterization of such crucial regulators advances our understanding of normal brain development and pathogenesis of diverse cognitive disorders.

  8. 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.

  9. The primary brain vesicles revisited: are the three primary vesicles (forebrain/midbrain/hindbrain) universal in vertebrates?

    PubMed

    Ishikawa, Yuji; Yamamoto, Naoyuki; Yoshimoto, Masami; Ito, Hironobu

    2012-01-01

    It is widely held that three primary brain vesicles (forebrain, midbrain, and hindbrain vesicles) develop into five secondary brain vesicles in all vertebrates (von Baer's scheme). We reviewed previous studies in various vertebrates to see if this currently accepted scheme of brain morphogenesis is a rule applicable to vertebrates in general. Classical morphological studies on lamprey, shark, zebrafish, frog, chick, Chinese hamster, and human embryos provide only partial evidence to support the existence of von Baer's primary vesicles at early stages. Rather, they suggest that early brain morphogenesis is diverse among vertebrates. Gene expression and fate map studies on medaka, chick, and mouse embryos show that the fates of initial brain vesicles do not accord with von Baer's scheme, at least in medaka and chick brains. The currently accepted von Baer's scheme of brain morphogenesis, therefore, is not a universal rule throughout vertebrates. We propose here a developmental hourglass model as an alternative general rule: Brain morphogenesis is highly conserved at the five-brain vesicle stage but diverges more extensively at earlier and later stages. This hypothesis does not preclude the existence of deep similarities in molecular prepatterns at early stages. Copyright © 2012 S. Karger AG, Basel.

  10. Zebrafish eleutheroembryos as an alternative system for screening chemicals disrupting the mammalian thyroid gland morphogenesis and function.

    PubMed

    Raldúa, Demetrio; Thienpont, Benedicte; Babin, Patrick J

    2012-04-01

    The importance and irreversibility of the effects of thyroid hormone deficiency on human brain development highlight the importance of identifying environmental agents that interfere with thyroid gland morphogenesis and function. Zebrafish eleutheroembryos are currently used by many pharmaceutical companies in drug discovery as a vertebrate model, not subjected to regulations for animal experiments, that provides an intermediate step between in vitro and rodent assay. The mechanisms of zebrafish thyroid development are generally comparable to those in humans, and moreover, molecular and functional studies of zebrafish thyroid follicles have demonstrated a high degree of conservation with upper vertebrates, opening up the possibility of designing alternative methods for screening individual chemicals and mixtures that impairing thyroid gland morphogenesis and/or function. Analysis of the intrafollicular thyroxine-content of zebrafish larvae exposed to potential disruptors has proved to be a reliable, physiologically relevant endpoint to estimate effects of chemicals on the mammalian thyroid gland.

  11. Activation of autophagy via Ca(2+)-dependent AMPK/mTOR pathway in rat notochordal cells is a cellular adaptation under hyperosmotic stress.

    PubMed

    Jiang, Li-Bo; Cao, Lu; Yin, Xiao-Fan; Yasen, Miersalijiang; Yishake, Mumingjiang; Dong, Jian; Li, Xi-Lei

    2015-01-01

    Nucleus pulposus (NP) cells experience hyperosmotic stress in spinal discs; however, how these cells can survive in the hostile microenvironment remains unclear. Autophagy has been suggested to maintain cellular homeostasis under different stresses by degrading the cytoplasmic proteins and organelles. Here, we explored whether autophagy is a cellular adaptation in rat notochordal cells under hyperosmotic stress. Hyperosmotic stress was found to activate autophagy in a dose- and time-dependent manner. SQSTM1/P62 expression was decreased as the autophagy level increased. Transient Ca(2+) influx from intracellular stores and extracellular space was stimulated by hyperosmotic stress. Activation of AMPK and inhibition of p70S6K were observed under hyperosmotic conditions. However, intercellular Ca(2+) chelation inhibited the increase of LC3-II and partly reversed the decrease of p70S6K. Hyperosmotic stress decreased cell viability and promoted apoptosis. Inhibition of autophagy led to SQSTM1/P62 accumulation, reduced cell viability, and accelerated apoptosis in notochordal cells under this condition. These evidences suggest that autophagy induction via the Ca(2+)-dependent AMPK/mTOR pathway might occur as an adaptation mechanism for notochordal cells under hyperosmotic stress. Thus, activating autophagy might be a promising approach to improve viability of notochordal cells in intervertebral discs.

  12. The 'Tully monster' is a vertebrate.

    PubMed

    McCoy, Victoria E; Saupe, Erin E; Lamsdell, James C; Tarhan, Lidya G; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G; Anderson, Ross P; Petermann, Holger; Locatelli, Emma R; Briggs, Derek E G

    2016-04-28

    Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica', particularly the 'weird wonders' of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.

  13. The Tully Monster is a Vertebrate

    SciTech Connect

    McCoy, Victoria E.; Saupe, Erin E.; Lamsdell, James C.; Tarhan, Lidya G.; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D.; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G.; Anderson, Ross P.; Petermann, Holger; Locatelli, Emma R.; Briggs, Derek E.G.

    2016-04-28

    Abstract Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the 'problem of the problematica'(1), particularly the 'weird wonders'(2) of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium(3), popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans(4,5), polychaetes(4), gastropods(4), conodonts(6), and the stem arthropod Opabinia(4). Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes(3-6). We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys(7-9), a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years

  14. 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

  15. Cellular dynamics and embryonic morphogenesis

    NASA Astrophysics Data System (ADS)

    Zallen, Jennifer

    2007-11-01

    The elongated body axis is a characteristic feature of many multicellular animals. Axis elongation occurs largely through cell rearrangements that are coordinated across a large cell population and driven by an asymmetric distribution of cytoskeletal and junctional proteins [1]. To visualize cellular dynamics during this process, we performed time-lapse confocal imaging of cell behavior in the Drosophila embryo. These studies revealed that rearranging cells display a steady increase in topological disorder that is accompanied by the formation of transient structures where 5-11 cells meet [2,3]. These multicellular rosettes form and resolve in a directional fashion to produce a local change in the aspect ratio of the cellular assembly, contributing to an overall change in tissue structure. We propose that higher-order rosette structures link local cell interactions to global tissue reorganization during morphogenesis. [1] J. Zallen and E. Wieschaus, Developmental Cell 6, 343 (2004). [2] J. Zallen and R. Zallen, J. Phys.: Condens. Matter 16, S5073 (2004). [3] J. Blankenship et al., Developmental Cell 11, 459 (2006).

  16. On the Morphogenesis of Feathers

    PubMed Central

    Yu, Mingke; Wu, Ping; Widelitz, Randall B.; Chuong, Cheng-Ming

    2015-01-01

    The most unique character of the feather is its highly ordered hierarchical branched structure1, 2. This evolutionary novelty confers flight function to birds3–5. Recent discoveries of fossils in China have prompted keen interest in the origin and evolution of feathers6–14. However, controversy arises whether the irregularly branched integumentary fibers on dinosaurs such as Sinornithosaurus are truly feathers6, 11, and whether an integumentary appendage with a major central shaft and notched edges is a non-avian feather or a proto-feather8–10. Here we take a developmental approach to analyze molecular mechanisms in feather branching morphogenesis. We have used the replication competent avian sarcoma (RCAS) retrovirus15 to efficiently deliver exogenous genes to regenerating chicken flight feather follicles. We show that the antagonistic balance between noggin and bone morphogenetic protein 4 (BMP4) plays 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 apoptosis of the marginal plate epithelia to become spaces between barbs. Our analyses show the molecular pathways underlying the topological transformation of feathers from cylindrical epithelia to the hierarchical branched structures, and provide first clues on the possible developmental mechanisms in the evolution of feather forms. PMID:12442169

  17. Lamprey metamorphosis: Thyroid hormone signaling in a basal vertebrate.

    PubMed

    Manzon, Richard G; Manzon, Lori A

    2017-06-16

    As one of the most basal living vertebrates, lampreys represent an excellent model system to study the evolution of thyroid hormone (TH) signaling. The lamprey hypothalamic-pituitary-thyroid and reproductive axes overlap functionally. Lampreys have 3 gonadotropin-releasing hormones and a single glycoprotein hormone from the hypothalamus and pituitary, respectively, that regulate both the reproductive and thyroid axes. TH synthesis in larval lampreys takes place in an endostyle that transforms into typical vertebrate thyroid tissue during metamorphosis; both the endostyle and follicular tissue have all the typical TH synthetic components found in other vertebrates. Furthermore, lampreys also have the vertebrate suite of peripheral regulators including TH distributor proteins (THDPs), deiodinases and TH receptors (TRs). Although at the molecular level the components of the lamprey thyroid system are ancestral to other vertebrates, their functions have been largely conserved. TH signaling as it relates to lamprey metamorphosis represents a particularly interesting phenomenon. Unlike other metamorphosing vertebrates, lamprey THs increase throughout the larval period, peak prior to metamorphosis and decline rapidly at the onset of metamorphosis; patterns of deiodinase activity are consistent with these increases and declines. Moreover, goitrogens (which suppress TH levels) initiate precocious metamorphosis, and exogenous TH treatment blocks goitrogen-induced metamorphosis and disrupts natural metamorphosis. Despite this clear physiological difference, TH action via TRs is consistent with higher vertebrates. Based on observations that TRs are upregulated in a tissue-specific fashion during morphogenesis and the finding that lamprey TRs upregulate genes via THs in a fashion similar to higher vertebrates, we propose the following hypothesis for further testing. THs have a dual role in lampreys where high TH levels promote larval feeding and growth and then at the onset of

  18. Chordoma-derived cell line U-CH1-N recapitulates the biological properties of notochordal nucleus pulposus cells.

    PubMed

    Fujita, Nobuyuki; Suzuki, Satoshi; Watanabe, Kota; Ishii, Ken; Watanabe, Ryuichi; Shimoda, Masayuki; Takubo, Keiyo; Tsuji, Takashi; Toyama, Yoshiaki; Miyamoto, Takeshi; Horiuchi, Keisuke; Nakamura, Masaya; Matsumoto, Morio

    2016-08-01

    Intervertebral disc degeneration proceeds with age and is one of the major causes of lumbar pain and degenerative lumbar spine diseases. However, studies in the field of intervertebral disc biology have been hampered by the lack of reliable cell lines that can be used for in vitro assays. In this study, we show that a chordoma-derived cell line U-CH1-N cells highly express the nucleus pulposus (NP) marker genes, including T (encodes T brachyury transcription factor), KRT19, and CD24. These observations were further confirmed by immunocytochemistry and flow cytometry. Reporter analyses showed that transcriptional activity of T was enhanced in U-CH1-N cells. Chondrogenic capacity of U-CH1-N cells was verified by evaluating the expression of extracellular matrix (ECM) genes and Alcian blue staining. Of note, we found that proliferation and synthesis of chondrogenic ECM proteins were largely dependent on T in U-CH1-N cells. In accordance, knockdown of the T transcripts suppressed the expression of PCNA, a gene essential for DNA replication, and SOX5 and SOX6, the master regulators of chondrogenesis. On the other hand, the CD24-silenced cells showed no reduction in the mRNA expression level of the chondrogenic ECM genes. These results suggest that U-CH1-N shares important biological properties with notochordal NP cells and that T plays crucial roles in maintaining the notochordal NP cell-like phenotype in this cell line. Taken together, our data indicate that U-CH1-N may serve as a useful tool in studying the biology of intervertebral disc. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 34:1341-1350, 2016.

  19. Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

    PubMed

    Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

    2016-02-01

    During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development.

  20. Influenza virus morphogenesis and budding

    PubMed Central

    Nayak, Debi P.; Balogun, Rilwan A.; Yamada, Hiroshi; Zhou, Z. Hong; Barman, Subrata

    2009-01-01

    Influenza viruses are enveloped, negative stranded, segmented RNA viruses belonging to Orthomyxoviridae family. Each virion consists of three major subviral components, namely (i) a viral envelope decorated with three transmembrane proteins hemagglutinin (HA), neuraminidase (NA) and M2, (ii) an intermediate layer of matrix protein (M1), and (iii) an innermost helical viral ribonucleocapsid [vRNP] core formed by nucleoprotein (NP) and negative strand viral RNA (vRNA). Since complete virus particles are not found inside the cell, the processes of assembly, morphogenesis, budding and release of progeny virus particles at the plasma membrane of the infected cells are critically important for the production of infectious virions and pathogenesis of influenza viruses as well. Morphogenesis and budding require that all virus components must be brought to the budding site which is the apical plasma membrane in polarized epithelial cells whether in vitro cultured cells or in vivo infected animals. HA and NA forming the outer spikes on the viral envelope possess apical sorting signals and use exocytic pathways and lipid rafts for cell surface transport and apical sorting. NP also has apical determinant(s) and is probably transported to the apical budding site similarly via lipid rafts and/or through cortical actin microfilaments. M1 binds the NP and the exposed RNAs of vRNPs, as well as to the cytoplasmic tails (CT) and transmembrane (TM) domains of HA, NA and M2, and is likely brought to the budding site on the piggy-back of vRNP and transmembrane proteins. Budding processes involve bud initiation, bud growth and bud release. Presence of lipid rafts and assembly of viral components at the budding site can cause asymmetry of lipid bilayers and outward membrane bending leading to bud initiation and bud growth. Bud release requires fusion of the apposing viral and cellular membranes and scission of the virus buds from the infected cellular membrane. The processes involved in

  1. 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…

  2. 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…

  3. 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.

  4. Two T-box genes play independent and cooperative roles to regulate morphogenesis of ciliated Kupffer's vesicle in zebrafish.

    PubMed

    Amack, Jeffrey D; Wang, Xinghao; Yost, H Joseph

    2007-10-15

    The brain, heart and gastro-intestinal tract develop distinct left-right (LR) asymmetries. Asymmetric cilia-dependent fluid flow in the embryonic node in mouse, Kupffer's vesicle in zebrafish, notochordal plate in rabbit and gastrocoel roof plate in frog appears to be a conserved mechanism that directs LR asymmetric gene expression and establishes the orientation of organ asymmetry. However, the cellular processes and genetic pathways that control the formation of these essential ciliated structures are unknown. In zebrafish, migratory dorsal forerunner cells (DFCs) give rise to Kupffer's vesicle (KV), a ciliated epithelial sheet that forms a lumen and generates fluid flow. Using the epithelial marker atypical Protein Kinase C (aPKC) and other markers to analyze DFCs and KV cells, we describe a multi-step process by which DFCs form a functional KV. Using mutants and morpholinos, we show that two T-box transcription factors-No tail (Ntl)/Brachyury and Tbx16/Spadetail-cooperatively regulate an early step of DFC mesenchyme to epithelial transition (MET) and KV cell specification. Subsequently, each transcription factor independently controls a distinct step in KV formation: Tbx16 regulates apical clustering of KV cells and Ntl is necessary for KV lumen formation. By targeting morpholinos to DFCs, we show that these cell autonomous functions in KV morphogenesis are necessary for LR patterning throughout the embryo.

  5. Imaging embryonic morphogenesis in C. elegans.

    PubMed

    Hardin, Jeff

    2011-01-01

    The Caenorhabditis elegans embryo is well suited to morphogenetic analysis via modern microscopy, due to its short generation time, transparency, invariant lineage, and the ability to generate transgenic embryos expressing various fluorescent proteins. This chapter provides an overview of microscopy techniques for imaging embryonic morphogenesis, including making agar mounts, capturing four-dimensional (4D) data using Nomarski microscopy, imaging of actin in embryos, factors important for optimizing 4D fluorescence microscopy, and recent techniques that leverage fluorescence microscopy for intracellular imaging of cellular components during morphogenesis.

  6. Regulation of dendrite morphogenesis by extrinsic cues.

    PubMed

    Valnegri, Pamela; Puram, Sidharth V; Bonni, Azad

    2015-07-01

    Dendrites play a central role in the integration and flow of information in the nervous system. The morphogenesis and maturation of dendrites is hence an essential step in the establishment of neuronal connectivity. Recent studies have uncovered crucial functions for extrinsic cues in the development of dendrites. We review the contribution of secreted polypeptide growth factors, contact-mediated proteins, and neuronal activity in distinct phases of dendrite development. We also highlight how extrinsic cues influence local and global intracellular mechanisms of dendrite morphogenesis. Finally, we discuss how these studies have advanced our understanding of neuronal connectivity and have shed light on the pathogenesis of neurodevelopmental disorders.

  7. Gene expression throughout a vertebrate's embryogenesis

    PubMed Central

    2011-01-01

    Background Describing the patterns of gene expression during embryonic development has broadened our understanding of the processes and patterns that define morphogenesis. Yet gene expression patterns have not been described throughout vertebrate embryogenesis. This study presents statistical analyses of gene expression during all 40 developmental stages in the teleost Fundulus heteroclitus using four biological replicates per stage. Results Patterns of gene expression for 7,000 genes appear to be important as they recapitulate developmental timing. Among the 45% of genes with significant expression differences between pairs of temporally adjacent stages, significant differences in gene expression vary from as few as five to more than 660. Five adjacent stages have disproportionately more significant changes in gene expression (> 200 genes) relative to other stages: four to eight and eight to sixteen cell stages, onset of circulation, pre and post-hatch, and during complete yolk absorption. The fewest differences among adjacent stages occur during gastrulation. Yet, at stage 16, (pre-mid-gastrulation) the largest number of genes has peak expression. This stage has an over representation of genes in oxidative respiration and protein expression (ribosomes, translational genes and proteases). Unexpectedly, among all ribosomal genes, both strong positive and negative correlations occur. Similar correlated patterns of expression occur among all significant genes. Conclusions These data provide statistical support for the temporal dynamics of developmental gene expression during all stages of vertebrate development. PMID:21356103

  8. Analysis of cellular behavior and cytoskeletal dynamics reveal a constriction mechanism driving optic cup morphogenesis

    PubMed Central

    Nicolás-Pérez, María; Kuchling, Franz; Letelier, Joaquín; Polvillo, Rocío; Wittbrodt, Jochen; Martínez-Morales, Juan R

    2016-01-01

    Contractile actomyosin networks have been shown to power tissue morphogenesis. Although the basic cellular machinery generating mechanical tension appears largely conserved, tensions propagate in unique ways within each tissue. Here we use the vertebrate eye as a paradigm to investigate how tensions are generated and transmitted during the folding of a neuroepithelial layer. We record membrane pulsatile behavior and actomyosin dynamics during zebrafish optic cup morphogenesis by live imaging. We show that retinal neuroblasts undergo fast oscillations and that myosin condensation correlates with episodic contractions that progressively reduce basal feet area. Interference with lamc1 function impairs basal contractility and optic cup folding. Mapping of tensile forces by laser cutting uncover a developmental window in which local ablations trigger the displacement of the entire tissue. Our work shows that optic cup morphogenesis is driven by a constriction mechanism and indicates that supra-cellular transmission of mechanical tension depends on ECM attachment. DOI: http://dx.doi.org/10.7554/eLife.15797.001 PMID:27797321

  9. How proteases regulate bone morphogenesis.

    PubMed

    Ortega, Nathalie; Behonick, Danielle; Stickens, Dominique; Werb, Zena

    2003-05-01

    Matrix metalloproteinases (MMPs) degrade most components of the extracellular matrix (ECM), as well as many non-ECM molecules. MMPs participate in (1). degradation of ECM to allow cell migration; (2). alteration of the ECM microenvironment resulting in alteration in cellular behavior; (3). modulation of biologically active molecules by direct cleavage or release from ECM stores; (4). regulation of the activity of other proteases; and (5). cell attachment, proliferation, differentiation, and apoptosis. We have sought to understand the role of MMPs during development and tissue repair in transgenic mice. Endochondral bone formation presents a particularly interesting developmental challenge. During this process, an avascular tissue (cartilage) is converted into one of the most highly vascularized tissues (bone) in the vertebrate body. Ossification begins with invasion of the calcified hypertrophic cartilage by capillaries. Apoptosis of the terminal hypertrophic chondrocytes, degradation of the cartilage matrix, and deposition of bone matrix by osteoblasts accompanies neovascularization of the growth plate. Remodeling of ECM results in a cavity filled with vascular channels containing hematopoietic cells. Our results reveal that MMP9, MMP13, and vascular endothelial growth factor are key regulators for the remodeling of the skeletal tissues. They coordinate not only matrix degradation, but also the recruitment and differentiation of endothelial cells, osteoclasts, chondroclasts, and osteoprogenitors.

  10. Neurogenesis and Morphogenesis in the Cerebellar Cortex*

    PubMed Central

    Eccles, J. C.

    1970-01-01

    The cerebellum presents the best site in the central nervous system for defining fundamental problems concerning the origin and differentiation of neurones, and their growth and development. The many recent experimental investigations of these problems are reviewed, and hypotheses based upon them are developed in relation to neurogenesis, morphogenesis, and synaptogenesis. PMID:4915885

  11. Vertebral Compression Fractures

    MedlinePlus

    ... OI: Information on Vertebral Compression Fractures 804 W. Diamond Ave., Ste. 210 Gaithersburg, MD 20878 (800) 981- ... osteogenesis imperfecta contact : Osteogenesis Imperfecta Foundation 804 W. Diamond Avenue, Suite 210, Gaithersburg, MD 20878 Tel: 800- ...

  12. Compartmentalization of vertebrate optic neuroephithelium: external cues and transcription factors.

    PubMed

    Kim, Hyoung-Tai; Kim, Jin Woo

    2012-04-01

    The vertebrate eye is a laterally extended structure of the forebrain. It develops through a series of events, including specification and regionalization of the anterior neural plate, evagination of the optic vesicle (OV), and development of three distinct optic structures: the neural retina (NR), optic stalk (OS), and retinal pigment epithelium (RPE). Various external signals that act on the optic neuroepithelium in a spatial- and temporal-specific manner control the fates of OV subdomains by inducing localized expression of key transcription factors. Investigating the mechanisms underlying compartmentalization of these distinct optic neuroepithelium-derived tissues is therefore not only important from the standpoint of accounting for vertebrate eye morphogenesis, it is also helpful for understanding the fundamental basis of fate determination of other neuroectoderm- derived tissues. This review focuses on the molecular signatures of OV subdomains and the external factors that direct the development of tissues originating from the OV.

  13. Cytoskeleton and Morphogenesis in Brown Algae

    PubMed Central

    KATSAROS, CHRISTOS; KARYOPHYLLIS, DEMOSTHENES; GALATIS, BASIL

    2006-01-01

    • Background Morphogenesis on a cellular level includes processes in which cytoskeleton and cell wall expansion are strongly involved. In brown algal zygotes, microtubules (MTs) and actin filaments (AFs) participate in polarity axis fixation, cell division and tip growth. Brown algal vegetative cells lack a cortical MT cytoskeleton, and are characterized by centriole-bearing centrosomes, which function as microtubule organizing centres. • Scope Extensive electron microscope and immunofluorescence studies of MT organization in different types of brown algal cells have shown that MTs constitute a major cytoskeletal component, indispensable for cell morphogenesis. Apart from participating in mitosis and cytokinesis, they are also involved in the expression and maintenance of polarity of particular cell types. Disruption of MTs after Nocodazole treatment inhibits cell growth, causing bulging and/or bending of apical cells, thickening of the tip cell wall, and affecting the nuclear positioning. Staining of F-actin using Rhodamine-Phalloidin, revealed a rich network consisting of perinuclear, endoplasmic and cortical AFs. AFs participate in mitosis by the organization of an F-actin spindle and in cytokinesis by an F-actin disc. They are also involved in the maintenance of polarity of apical cells, as well as in lateral branch initiation. The cortical system of AFs was found related to the orientation of cellulose microfibrils (MFs), and therefore to cell wall morphogenesis. This is expressed by the coincidence in the orientation between cortical AFs and the depositing MFs. Treatment with cytochalasin B inhibits mitosis and cytokinesis, as well as tip growth of apical cells, and causes abnormal deposition of MFs. • Conclusions Both the cytoskeletal elements studied so far, i.e. MTs and AFs are implicated in brown algal cell morphogenesis, expressed in their relationship with cell wall morphogenesis, polarization, spindle organization and cytokinetic mechanism. The

  14. In vivo Analysis of Choroid Plexus Morphogenesis in Zebrafish

    PubMed Central

    Fong, Steven H.; Ye, Zhang-Rui; Korzh, Vladimir

    2008-01-01

    Background The choroid plexus (ChP), a component of the blood-brain barrier (BBB), produces the cerebrospinal fluid (CSF) and as a result plays a role in (i) protecting and nurturing the brain as well as (ii) in coordinating neuronal migration during neurodevelopment. Until now ChP development was not analyzed in living vertebrates due to technical problems. Methodology/Principal Findings We have analyzed the formation of the fourth ventricle ChP of zebrafish in the GFP-tagged enhancer trap transgenic line SqET33-E20 (Gateways) by a combination of in vivo imaging, histology and mutant analysis. This process includes the formation of the tela choroidea (TC), the recruitment of cells from rhombic lips and, finally, the coalescence of TC resulting in formation of ChP. In Notch-deficient mib mutants the first phase of this process is affected with premature GFP expression, deficient cell recruitment into TC and abnormal patterning of ChP. In Hedgehog-deficient smu mutants the second phase of the ChP morphogenesis lacks cell recruitment and TC cells undergo apoptosis. Conclusions/Significance This study is the first to demonstrate the formation of ChP in vivo revealing a role of Notch and Hedgehog signalling pathways during different developmental phases of this process. PMID:18769618

  15. Split top: a maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

    PubMed Central

    Langdon, Yvette G.; Fuentes, Ricardo; Zhang, Hong; Abrams, Elliott W.; Marlow, Florence L.; Mullins, Mary C.

    2016-01-01

    The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel

  16. Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling

    PubMed Central

    Gibbs, Holly C.; Chang-Gonzalez, Ana; Hwang, Wonmuk; Yeh, Alvin T.; Lekven, Arne C.

    2017-01-01

    A constriction in the neural tube at the junction of the midbrain and hindbrain is a conserved feature of vertebrate embryos. The constriction is a defining feature of the midbrain-hindbrain boundary (MHB), a signaling center that patterns the adjacent midbrain and rostral hindbrain and forms at the junction of two gene expression domains in the early neural plate: an anterior otx2/wnt1 positive domain and a posterior gbx/fgf8 positive domain. otx2 and gbx genes encode mutually repressive transcription factors that create a lineage restriction boundary at their expression interface. Wnt and Fgf genes form a mutually dependent feedback system that maintains their expression domains on the otx2 or gbx side of the boundary, respectively. Constriction morphogenesis occurs after these conserved gene expression domains are established and while their mutual interactions maintain their expression pattern; consequently, mutant studies in zebrafish have led to the suggestion that constriction morphogenesis should be considered a unique phase of MHB development. We analyzed MHB morphogenesis in fgf8 loss of function zebrafish embryos using a reporter driven by the conserved wnt1 enhancer to visualize anterior boundary cells. We found that fgf8 loss of function results in a re-activation of wnt1 reporter expression posterior to the boundary simultaneous with an inactivation of the wnt1 reporter in the anterior boundary cells, and that these events correlate with relaxation of the boundary constriction. In consideration of other results that correlate the boundary constriction with Wnt and Fgf expression, we propose that the maintenance of an active Wnt-Fgf feedback loop is a key factor in driving the morphogenesis of the MHB constriction. PMID:28824384

  17. Fgfr signaling is required as the early eye field forms to promote later patterning and morphogenesis of the eye.

    PubMed

    Atkinson-Leadbeater, K; Hehr, C L; Mcfarlane, S

    2014-05-01

    A major step in eye morphogenesis is the transition from optic vesicle to optic cup, which occurs as a ventral groove forms along the base of the optic vesicle. A ventral gap in the eye, or coloboma, results when this groove fails to close. Extrinsic signals, such as fibroblast growth factors (Fgfs), play a critical role in the development and morphogenesis of the vertebrate eye. Whether these extrinsic signals are required throughout eye development, or within a defined critical period remains an unanswered question. Here we show that an early Fgf signal, required as the eye field is first emerging, drives eye morphogenesis. In addition to triggering coloboma, inhibition of this early Fgf signal results in defects in dorsal-ventral patterning of the neural retina, particularly in the nasal retina, and development of the periocular mesenchyme (POM). These processes are unaffected by inhibition of Fgfr signaling at later time points. We propose that Fgfs act within an early critical period as the eye field forms to promote development of the neural retina and POM, which subsequently drive eye morphogenesis. Copyright © 2014 Wiley Periodicals, Inc.

  18. Failure of articular process (zygaphophyseal) joint development as a cause of vertebral fusion (blocked vertebrae).

    PubMed Central

    Chandraraj, S

    1987-01-01

    Examination of congenitally fused (blocked) vertebrae in this study suggests that non-development of the joint between articular facets results in fusion of the vertebral arches which in turn leads to secondary fusion of the bodies and hypoplasia of the intervertebral discs. The presence of independent pedicles and transverse processes do not favour the concept that such an abnormality is the result of non-segmentation of the sclerotome. The condition is probably linked to a defect of an inductor substance which influences normal morphogenesis of the vertebral arch in the embryonic period. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:3429327

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

    PubMed

    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.

  20. 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

  1. A complex choreography of cell movements shapes the vertebrate eye.

    PubMed

    Kwan, Kristen M; Otsuna, Hideo; Kidokoro, Hinako; Carney, Keith R; Saijoh, Yukio; Chien, Chi-Bin

    2012-01-01

    Optic cup morphogenesis (OCM) generates the basic structure of the vertebrate eye. Although it is commonly depicted as a series of epithelial sheet folding events, this does not represent an empirically supported model. Here, we combine four-dimensional imaging with custom cell tracking software and photoactivatable fluorophore labeling to determine the cellular dynamics underlying OCM in zebrafish. Although cell division contributes to growth, we find it dispensable for eye formation. OCM depends instead on a complex set of cell movements coordinated between the prospective neural retina, retinal pigmented epithelium (RPE) and lens. Optic vesicle evagination persists for longer than expected; cells move in a pinwheel pattern during optic vesicle elongation and retinal precursors involute around the rim of the invaginating optic cup. We identify unanticipated movements, particularly of central and peripheral retina, RPE and lens. From cell tracking data, we generate retina, RPE and lens subdomain fate maps, which reveal novel adjacencies that might determine corresponding developmental signaling events. Finally, we find that similar movements also occur during chick eye morphogenesis, suggesting that the underlying choreography is conserved among vertebrates.

  2. The maternal genes Ci-p53/p73-a and Ci-p53/p73-b regulate zygotic ZicL expression and notochord differentiation in Ciona intestinalis embryos.

    PubMed

    Noda, Takeshi

    2011-12-01

    I isolated a Ciona intestinalis homolog of p53, Ci-p53/p73-a, in a microarray screen of rapidly degraded maternal mRNA by comparing the transcriptomes of unfertilized eggs and 32-cell stage embryos. Higher expression of the gene in eggs and lower expression in later embryonic stages were confirmed by whole-mount in situ hybridization (WISH) and quantitative reverse transcription-PCR (qRT-PCR); expression was ubiquitous in eggs and early embryos. Knockdown of Ci-p53/p73-a by injection of antisense morpholino oligonucleotides (MOs) severely perturbed gastrulation cell movements and expression of notochord marker genes. A key regulator of notochord differentiation in Ciona embryos is Brachyury (Ci-Bra), which is directly activated by a zic-like gene (Ci-ZicL). The expression of Ci-ZicL and Ci-Bra in A-line notochord precursors was downregulated in Ci-p53/p73-a knockdown embryos. Maternal expression of Ci-p53/p73-b, a homolog of Ci-p53/p73-a, was also detected. In Ci-p53/p73-b knockdown embryos, gastrulation cell movements, expression of Ci-ZicL and Ci-Bra in A-line notochord precursors, and expression of notochord marker gene at later stages were perturbed. The upstream region of Ci-ZicL contains putative p53-binding sites. Cis-regulatory analysis of Ci-ZicL showed that these sites are involved in expression of Ci-ZicL in A-line notochord precursors at the 32-cell and early gastrula stages. These results suggest that p53 genes are maternal factors that play a crucial role in A-line notochord differentiation in C. intestinalis embryos by regulating Ci-ZicL expression.

  3. Localization of Proliferating Cells in the Inter-Vertebral Region of the Developing and Adult Vertebrae of Lizards in Relation to Growth and Regeneration.

    PubMed

    Alibardi, Lorenzo

    2016-04-01

    New cartilaginous tissues in lizards is formed during the regeneration of the tail or after vertebral damage. In order to understand the origin of new cartilaginous cells in the embryo and after injury of adult vertebrae we have studied the distribution of proliferating cartilaginous cells in the vertebral column of embryos and adults of the lizard Anolis lineatopus using autoradiography for H3-thymidine and light and ultrastructural immunocytochemistry for 5BrdU. Proliferating sclerotomal cells initially surround the notochord in a segmental pattern and give rise to the chondrocytes of the vertebral centrum that replace the original chordal cells. Qualitative observations show that proliferating sclerotomal cells dilute the labeling up to 13 days post-injection but a few maintain the labeling as long labeling retention cells and remain in the inter-centra and perichondrium after birth. These cells supply new chondroblasts for post-natal growth of vertebrae but can also proliferate in case of vertebral damage or tail amputation in lizards, a process that sustains tail regeneration. The lack of somitic organization in the regenerating tail impedes the re-formation of a segmental vertebral column that is instead replaced by a continuous cartilaginous tube. It is hypothesized that long labeling retaining cells might represent stem/primordial cells, and that their permanence in the inter-vertebral cartilages and the nearby perichondrium in adult lizards pre-adapt these reptiles to elicit a broad cartilage regeneration in case of injury of the vertebrae. © 2016 Wiley Periodicals, Inc.

  4. Kinship affects morphogenesis in cannibalistic salamanders.

    PubMed

    Pfennig, D W; Collins, J P

    1993-04-29

    Inclusive fitness theory predicts that organisms can often increase their fitness by helping relatives. Indeed, many animals modify their behaviour towards kin in a fashion consistent with theory. Morphogenesis may also be sensitive to kinship environment, especially in species that facultatively produce distinct morphs that differ in their ability to harm relatives, such as those that produce alternative cannibalistic and non-cannibalistic phenotypes. We tested this hypothesis by examining whether consanguinity affected the probability that structurally distinctive cannibal morphs would develop in larval Arizona tiger salamanders (Ambystoma tigrinum nebulosum). We report here that when tiger salamander larvae are reared in mixed-brood groups they are significantly more likely to develop the cannibal morphology and at an earlier age than siblings reared in pure-sibship groups. In general, morphogenesis may be responsive to kinship in any species that facultatively develops structures that can be used against conspecifics as weaponry.

  5. Mechanics of epithelial tissue homeostasis and morphogenesis.

    PubMed

    Guillot, Charlène; Lecuit, Thomas

    2013-06-07

    Epithelia are robust tissues that support the structure of embryos and organs and serve as effective barriers against pathogens. Epithelia also chemically separate different physiological environments. These vital functions require tight association between cells through the assembly of junctions that mechanically stabilize the tissue. Remarkably, epithelia are also dynamic and can display a fluid behavior. Cells continuously die or divide, thereby allowing functional tissue homeostasis. Epithelial cells can change shape or intercalate as tissues deform during morphogenesis. We review the mechanical basis of tissue robustness and fluidity, with an emphasis on the pivotal role of junction dynamics. Tissue fluidity emerges from local active stresses acting at cell interfaces and allows the maintenance of epithelial organization during morphogenesis and tissue renewal.

  6. Computational Models for Mechanics of Morphogenesis

    PubMed Central

    Wyczalkowski, Matthew A.; Chen, Zi; Filas, Benjamen A.; Varner, Victor D.; Taber, Larry A.

    2012-01-01

    In the developing embryo, tissues differentiate, deform, and move in an orchestrated manner to generate various biological shapes driven by the complex interplay between genetic, epigenetic, and environmental factors. Mechanics plays a key role in regulating and controlling morphogenesis, and quantitative models help us understand how various mechanical forces combine to shape the embryo. Models allow for the quantitative, unbiased testing of physical mechanisms, and when used appropriately, can motivate new experimental directions. This knowledge benefits biomedical researchers who aim to prevent and treat congenital malformations, as well as engineers working to create replacement tissues in the laboratory. In this review, we first give an overview of fundamental mechanical theories for morphogenesis, and then focus on models for specific processes, including pattern formation, gastrulation, neurulation, organogenesis, and wound healing. The role of mechanical feedback in development is also discussed. Finally, some perspectives are given on the emerging challenges in morphomechanics and mechanobiology. PMID:22692887

  7. Peripheral nerve morphogenesis induced by scaffold micropatterning

    PubMed Central

    Memon, Danish; Boneschi, Filippo Martinelli; Madaghiele, Marta; Brambilla, Paola; Del Carro, Ubaldo; Taveggia, Carla; Riva, Nilo; Trimarco, Amelia; Lopez, Ignazio D.; Comi, Giancarlo; Pluchino, Stefano; Martino, Gianvito; Sannino, Alessandro; Quattrini, Angelo

    2014-01-01

    Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous microstructure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold’s microstructure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration. PMID:24559639

  8. 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

  9. 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

  10. Functional interactions between Fat family cadherins in tissue morphogenesis and planar polarity

    PubMed Central

    Saburi, Sakura; Hester, Ian; Goodrich, Lisa; McNeill, Helen

    2012-01-01

    The atypical cadherin fat (ft) was originally discovered as a tumor suppressor in Drosophila and later shown to regulate a form of tissue patterning known as planar polarity. In mammals, four ft homologs have been identified (Fat1-4). Recently, we demonstrated that Fat4 plays a role in vertebrate planar polarity. Fat4 has the highest homology to ft, whereas other Fat family members are homologous to the second ft-like gene, ft2. Genetic studies in flies and mice imply significant functional differences between the two groups of Fat cadherins. Here, we demonstrate that Fat family proteins act both synergistically and antagonistically to influence multiple aspects of tissue morphogenesis. We find that Fat1 and Fat4 cooperate during mouse development to control renal tubular elongation, cochlear extension, cranial neural tube formation and patterning of outer hair cells in the cochlea. Similarly, Fat3 and Fat4 synergize to drive vertebral arch fusion at the dorsal midline during caudal vertebra morphogenesis. We provide evidence that these effects depend on conserved interactions with planar polarity signaling components. In flies, the transcriptional co-repressor Atrophin (Atro) physically interacts with Ft and acts as a component of Fat signaling for planar polarity. We find that the mammalian orthologs of atro, Atn1 and Atn2l, modulate Fat4 activity during vertebral arch fusion and renal tubular elongation, respectively. Moreover, Fat4 morphogenetic defects are enhanced by mutations in Vangl2, a ‘core’ planar cell polarity gene. These studies highlight the wide range and complexity of Fat activities and suggest that a Fat-Atrophin interaction is a conserved element of planar polarity signaling. PMID:22510986

  11. Punctuated evolution and robustness in morphogenesis.

    PubMed

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

    2014-09-01

    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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Laminin is required for Schwann cell morphogenesis.

    PubMed

    Yu, Wei-Ming; Chen, Zu-Lin; North, Alison J; Strickland, Sidney

    2009-04-01

    Development of the peripheral nervous system requires radial axonal sorting by Schwann cells (SCs). To accomplish sorting, SCs must both proliferate and undergo morphogenetic changes such as process extension. Signaling studies reveal pathways that control either proliferation or morphogenesis, and laminin is essential for SC proliferation. However, it is not clear whether laminin is also required for SC morphogenesis. By using a novel time-lapse live-cell-imaging technique, we demonstrated that laminins are required for SCs to form a bipolar shape as well as for process extension. These morphological deficits are accompanied by alterations in signaling pathways. Phosphorylation of Schwannomin at serine 518 and activation of Rho GTPase Cdc42 and Rac1 were all significantly decreased in SCs lacking laminins. Inhibiting Rac1 and/or Cdc42 activities in cultured SCs attenuated laminin-induced myelination, whereas forced activation of Rac1 and/or Cdc42 in vivo improved sorting and hypomyelinating phenotypes in SCs lacking laminins. These findings indicate that laminins play a pivotal role in regulating SC cytoskeletal signaling. Coupled with previous results demonstrating that laminin is critical for SC proliferation, this work identifies laminin signaling as a central regulator coordinating the processes of proliferation and morphogenesis in radial axonal sorting.

  13. NRAGE: a potential rheostat during branching morphogenesis.

    PubMed

    Nikopoulos, George N; Martins, Joao Ferreira; Adams, Tamara L; Karaczyn, Aldona; Adams, Derek; Vary, Calvin; Oxburgh, Leif; Verdi, Joseph M

    2009-01-01

    Branching morphogenesis is a developmental process characteristic of many organ systems. Specifically, during renal branching morphogenesis, its been postulated that the final number of nephrons formed is one key clinical factor in the development of hypertension in adulthood. As it has been established that BMPs regulate, in part, renal activity of p38 MAP kinase (p38(MAPK)) and it has demonstrated that the cytoplasmic protein Neurotrophin Receptor MAGE homologue (NRAGE) augments p38(MAPK) activation, it was hypothesized that a decrease in the expression of NRAGE during renal branching would result in decreased branching of the UB that correlated with changes in p38(MAPK) activation. To verify this, the expression of NRAGE was reduced in ex vivo kidney explants cultures using antisense morpholino. Morpholino treated ex vivo kidney explants expression were severely stunted in branching, a trait that was rescued with the addition of exogenous GDNF. Renal explants also demonstrated a precipitous drop in p38(MAPK) activation that too was reversed in the presence of recombinant GDNF. RNA profiling of NRAGE diminished ex vivo kidney explants resulted in altered expression of GDNF, Ret, BMP7 and BMPRIb mRNAs. Our results suggested that in early kidney development NRAGE might have multiple roles during renal branching morphogenesis through association with both the BMP and GDNF signaling pathways.

  14. NRAGE: A Potential Rheostat During Branching Morphogenesis

    PubMed Central

    Nikopoulos, George N.; Martins, Joao Ferreira; Adams, Tamara L.; Karaczyn, Aldona; Adams, Derek; Vary, Calvin; Verdi, Joseph M.

    2009-01-01

    Branching morphogenesis is a developmental process characteristic of many organ systems. Specifically, during renal branching morphogenesis, its been postulated that the final number of nephrons formed is one key clinical factor in the development of hypertension in adulthood. As it has been established that BMPs regulate, in part, renal activity of p38 MAP kinase (p38MAPK) and it has demonstrated that the cytoplasmic protein Neurotrophin Receptor MAGE homologue (NRAGE) augments p38MAPK activation, it was hypothesized that a decrease in the expression of NRAGE during renal branching would result in decreased branching of the UB that correlated with changes in p38MAPK activation. To verify this, the expression of NRAGE was reduced in ex vivo kidney explants cultures using antisense morpholino. Morpholino treated ex vivo kidney explants expression were severely stunted in branching, a trait that was rescued with the addition of exogenous GDNF. Renal explants also demonstrated a precipitous drop in p38MAPK activation that too was reversed in the presence of recombinant GDNF. RNA profiling of NRAGE diminished ex vivo kidney explants resulted in altered expression of GDNF, Ret, BMP7 and BMPRIb mRNAs. Our results suggested that in early kidney development NRAGE might have multiple roles during renal branching morphogenesis through association with both the BMP and GDNF signaling pathways. PMID:19268530

  15. 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

  16. 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

  17. Mechanobiological simulations of prenatal joint morphogenesis.

    PubMed

    Giorgi, Mario; Carriero, Alessandra; Shefelbine, Sandra J; Nowlan, Niamh C

    2014-03-21

    Joint morphogenesis is the process in which prenatal joints acquire their reciprocal and interlocking shapes. Despite the clinical importance of the process, it remains unclear how joints acquire their shapes. In this study, we simulate 3D mechanobiological joint morphogenesis for which the effects of a range of movements (or lack of movement) and different initial joint shapes are explored. We propose that static hydrostatic compression inhibits cartilage growth while dynamic hydrostatic compression promotes cartilage growth. Both pre-cavitational (no muscle contractions) and post-cavitational (with muscle contractions) phases of joint development were simulated. Our results showed that for hinge type motion (planar motion from 45° to 120°) the proximal joint surface developed a convex profile in the posterior region and the distal joint surface developed a slightly concave profile. When 3D movements from 40° to -40° in two planes were applied, simulating a rotational movement, the proximal joint surface developed a concave profile whereas the distal joint surface rudiment acquire a rounded convex profile, showing an interlocking shape typical of a ball and socket joint. The significance of this research is that it provides new and important insights into normal and abnormal joint development, and contributes to our understanding of the mechanical factors driving very early joint morphogenesis. An enhanced understanding of how prenatal joints form is critical for developing strategies for early diagnosis and preventative treatments for congenital musculoskeletal abnormalities such as developmental dysplasia of the hip.

  18. Incidental vertebral lesions.

    PubMed

    Coumans, Jean-Valery C E; Walcott, Brian P

    2011-12-01

    Incidental vertebral lesions on imaging of the spine are commonly encountered in clinical practice. Contributing factors include the aging population, the increasing prevalence of back pain, and increased usage of MR imaging. Additionally, refinements in CT and MR imaging have increased the number of demonstrable lesions. The management of incidental findings varies among practitioners and commonly depends more on practice style than on data or guidelines. In this article we review incidental findings within the vertebral column and review management of these lesions, based on available Class III data.

  19. Autophagy during vertebrate development.

    PubMed

    Aburto, María R; Hurlé, Juan M; Varela-Nieto, Isabel; Magariños, Marta

    2012-08-02

    Autophagy is an evolutionarily conserved catabolic process by which cells degrade their own components through the lysosomal machinery. In physiological conditions, the mechanism is tightly regulated and contributes to maintain a balance between synthesis and degradation in cells undergoing intense metabolic activities. Autophagy is associated with major tissue remodeling processes occurring through the embryonic, fetal and early postnatal periods of vertebrates. Here we survey current information implicating autophagy in cellular death, proliferation or differentiation in developing vertebrates. In developing systems, activation of the autophagic machinery could promote different outcomes depending on the cellular context. Autophagy is thus an extraordinary tool for the developing organs and tissues.

  20. Planar polarity, tissue polarity and planar morphogenesis in plants.

    PubMed

    Nakamura, Moritaka; Kiefer, Christian S; Grebe, Markus

    2012-12-01

    Plant tissues commonly undergo morphogenesis within a single tissue layer or between associated cells of the same tissue type such as vascular cells. Tissue morphogenesis may rely on an underlying tissue polarity marked by coordinated unidirectional asymmetric localisation of molecules to ends of cells. When observed in the plane of the tissue layer this is referred to as planar polarity and planar morphogenesis. However, planar morphogenesis can also involve multidirectional or differential growth of cells relying on cell-cell communication. Here, we review recent progress towards an understanding of hormonal coordination and molecular mechanisms underlying planar and tissue polarity as well as planar morphogenesis. Furthermore, we discuss the role of physical forces in planar morphogenesis and the contribution of tissue polarity to plant organ shape. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Vertebral-Basilar Insufficiency

    PubMed Central

    Cape, Ronald D. T.; Hogan, David B.

    1983-01-01

    Vertebral-basilar ischemia can result in giddiness, transient ischemic attacks, and drop attacks. Management involves controlling blood pressure, getting the patient to stop smoking, controlling diabetes and/or hyperlipidemia, and instituting antiplatelet therapy. Several facets of this problem remain unexplained. PMID:21283322

  2. Demonstration of abnormal notochord development by three-dimensional reconstructive imaging in the rat model of esophageal atresia.

    PubMed

    Williams, A K; Qi, B Q; Beasley, S W

    2001-01-01

    The notochord (Nt) is believed to have a role in the development of axial organs. This study was undertaken to reconstruct in three dimensions (3D) the relationship of the Nt to abnormal development of the foregut (Fg) in the adriamycin-induced rat model of esophageal atresia (EA). Pregnant Sprague-Dawley rats were given 1.75 mg/kg adriamycin intraperitoneally on gestational days 6 9 inclusive; control rats received i.p. saline of equal volume, or no injection. Rats were killed between days 11 and 14 and their embryos harvested, histologically sectioned serially, and stained with hematoxylin and eosin. Digitized photographs were taken of serial transverse sections; these photos were traced and used as the basis for 3D reconstruction. From day 11 the normal Nt is no longer in contact with the respiratory or Fg mesenchyme. In adriamycin-treated embryos the Nt branches abnormally as it enters the Fg mesenchyme. Adherence of the Nt to the mesenchyme of the Fg exerts mechanical traction pulling the upper Fg dorsally. The severity of the Fg abnormalities correlates with the length of the ventral extension of the Nt within the Fg mesenchyme: the embryo develops atresia of the esophagus or trachea when the Nt is grossly abnormal. The Nt undergoes reactive thickening in the absence of Fg structures ventral to it. Thus, structural lesions of the Fg (e.g., atresias) are associated with abnormalities of the Nt. The relationship of the Nt to the Fg mesenchyme determines the severity of the abnormality induced by adriamycin: extensive adherence produces tracheal agenesis and EA.

  3. Can notochordal cells promote bone marrow stromal cell potential for nucleus pulposus enrichment? A simplified in vitro system.

    PubMed

    Potier, Esther; Ito, Keita

    2014-12-01

    Bone marrow stromal cells (BMSCs) have shown promising potential to stop intervertebral disc degeneration in several animal models. In order to restore a healthy state, though, this potential should be further stimulated. Notochordal cells (NCs), influential in disc development, have been shown to stimulate BMSC differentiation, but it is unclear how this effect will translate in an environment where resident disc cells (nucleus pulposus cells [NPCs]) could also influence BMSCs. The goal of this study was, therefore, to evaluate the effects of NCs on BMSCs when cocultured with NPCs, in a simplified 3D in vitro system. Bovine BMSCs and NPCs were mixed (Mix) and seeded into alginate beads. Using culture inserts, the Mix was then cocultured with porcine NCs (alginate beads) and compared to coculture with empty beads or porcine skin fibroblasts (SFs, alginate beads). NPCs alone were also cocultured with NCs, and BMSCs alone cultured under chondrogenic conditions. The effects of coculture conditions on cell viability, matrix production (proteoglycan and collagen), and gene expression of disc markers (aggrecan, type II collagen, and SOX9) were assessed after 4 weeks of culture. The NC phenotype and gene expression profile were also analyzed. Coculture with NCs did not significantly influence cell viability, proteoglycan production, or disc marker gene expression of the Mix. When compared to NPCs, the Mix produced the same amount of proteoglycan and displayed a higher expression of disc marker, indicating a stimulation of the BMSCs (and/or NPCs) in the Mix. Additionally, during the 4 weeks of culture, the NC phenotype changed drastically (morphology, gene expression profile). These results show that NCs might not be as stimulatory for BMSCs in an NPC-rich environment, as believed from individual cultures. This absence of effects could be explained by a mild stimulation provided by (de)differentiating NCs and the costimulation of BMSCs and NPCs by each other.

  4. 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

  5. Normal morphogenesis of epithelial tissues and progression of epithelial tumors.

    PubMed

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

    2012-01-01

    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.

  6. Soluble factors from the notochordal-rich intervertebral disc inhibit endothelial cell invasion and vessel formation in the presence and absence of pro-inflammatory cytokines

    PubMed Central

    Cornejo, M.C.; Cho, S.K.; Giannarelli, C.; Iatridis, J.C.; Purmessur, D.

    2015-01-01

    Background Chronic low back pain can be associated with the pathological ingrowth of blood vessels and nerves into intervertebral discs (IVDs). The notochord patterns the IVD during development and is a source of anti-angiogenic soluble factors such as Noggin and Chondroitin sulfate (CS). These factors may form the basis for a new minimally invasive strategy to target angiogenesis in the IVD. Objective To examine the anti-angiogenic potential of soluble factors from notochordal cells (NCs) and candidates Noggin and CS under healthy culture conditions and in the presence of pro-inflammatory mediators. Design NC conditioned media (NCCM) was generated from porcine NC-rich nucleus pulposus tissue. To assess the effects of NCCM, CS and Noggin on angiogenesis, cell invasion and tubular formation assays were performed using human umbilical vein endothelial cells (HUVECs) ± tumor necrosis factor alpha (TNFα [10 ng/ml]). vascular endothelial growth factor (VEGF)-A, MMP-7, interleukin-6 (IL-6) and IL-8 mRNA levels were assessed using qRT-PCR. Results NCCM (10 & 100%), CS (10 and 100 μg) and Noggin (10 and 100 ng) significantly decreased cell invasion of HUVECs with and without TNFα. NCCM 10% and Noggin 10 ng inhibited tubular formation with and without TNFα and CS 100 μg inhibited tubules in Basal conditions whereas CS 10 μg inhibited tubules with TNFα. NCCM significantly decreased VEGF-A, MMP-7 and IL-6 mRNA levels in HUVECs with and without TNFα. CS and Noggin had no effects on gene expression. Conclusions We provide the first evidence that soluble factors from NCs can inhibit angiogenesis by suppressing VEGF signaling. Notochordal-derived ligands are a promising minimally invasive strategy targeting neurovascular ingrowth and pain in the degenerated IVD. PMID:25534363

  7. pdzrn3 is required for pronephros morphogenesis in Xenopus laevis.

    PubMed

    Marracci, Silvia; Vangelisti, Alberto; Raffa, Vittoria; Andreazzoli, Massimiliano; Dente, Luciana

    2016-01-01

    Pdzrn3, a multidomain protein with E3-ubiquitin ligase activity, has been reported to play a role in myoblast and osteoblast differentiation and, more recently, in neuronal and endothelial cell development. The expression of the pdzrn3 gene is developmentally regulated in various vertebrate tissues, including muscular, neural and vascular system. Little is known about its expression during kidney development, although genetic polymorphisms and alterations around the human pdzrn3 chromosomal region have been found to be associated with renal cell carcinomas and other kidney diseases. We investigated the pdzrn3 spatio-temporal expression pattern in Xenopus laevis embryos by in situ hybridization. We focused our study on the development of the pronephros, which is the embryonic amphibian kidney, functionally similar to the most primitive nephric structures of human kidney. To explore the role of pdzrn3 during renal morphogenesis, we performed loss-of-function experiments, through antisense morpholino injections and analysed the morphants using specific pronephric markers. Dynamic pdzrn3 expression was observed in embryonic tissues, such as somites, brain, eye, blood islands, heart, liver and pronephros. Loss of function experiments resulted in specific alterations of pronephros development. In particular, at early stages, pdzrn3 depletion was associated with a reduction of the pronephros anlagen and later, with perturbations of the tubulogenesis, including deformation of the proximal tubules. Rescue experiments, in which mRNA of the zebrafish pdzrn3 orthologue was injected together with the morpholino, allowed recovery of the kidney phenotypes. These results underline the importance of pdzrn3 expression for correct nephrogenesis.

  8. Mathematical modeling of vertebrate limb development.

    PubMed

    Zhang, Yong-Tao; Alber, Mark S; Newman, Stuart A

    2013-05-01

    In this paper, we review the major mathematical and computational models of vertebrate limb development and their roles in accounting for different aspects of this process. The main aspects of limb development that have been modeled include outgrowth and shaping of the limb bud, establishment of molecular gradients within the bud, and formation of the skeleton. These processes occur interdependently during development, although (as described in this review), there are various interpretations of the biological relationships among them. A wide range of mathematical and computational methods have been used to study these processes, including ordinary and partial differential equation systems, cellular automata and discrete, stochastic models, finite difference methods, finite element methods, the immersed boundary method, and various combinations of the above. Multiscale mathematical modeling and associated computational simulation have become integrated into the study of limb morphogenesis and pattern formation to an extent with few parallels in the field of developmental biology. These methods have contributed to the design and analysis of experiments employing microsurgical and genetic manipulations, evaluation of hypotheses for limb bud outgrowth, interpretation of the effects of natural mutations, and the formulation of scenarios for the origination and evolution of the limb skeleton.

  9. 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.

  10. 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.

  11. 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).

  12. 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.

  13. Intrinsic and extrinsic mechanisms of dendritic morphogenesis.

    PubMed

    Dong, Xintong; Shen, Kang; Bülow, Hannes E

    2015-01-01

    The complex, branched morphology of dendrites is a cardinal feature of neurons and has been used as a criterion for cell type identification since the beginning of neurobiology. Regulated dendritic outgrowth and branching during development form the basis of receptive fields for neurons and are essential for the wiring of the nervous system. The cellular and molecular mechanisms of dendritic morphogenesis have been an intensely studied area. In this review, we summarize the major experimental systems that have contributed to our understandings of dendritic development as well as the intrinsic and extrinsic mechanisms that instruct the neurons to form cell type-specific dendritic arbors.

  14. Extracellular matrix signaling in morphogenesis and repair.

    PubMed

    Clause, Kelly C; Barker, Thomas H

    2013-10-01

    The extracellular matrix (ECM) is critically important for many cellular processes including growth, differentiation, survival, and morphogenesis. Cells remodel and reshape the ECM by degrading and reassembling it, playing an active role in sculpting their surrounding environment and directing their own phenotypes. Both mechanical and biochemical molecules influence ECM dynamics in multiple ways; by releasing small bioactive signaling molecules, releasing growth factors stored within the ECM, eliciting structural changes to matrix proteins which expose cryptic sites and by degrading matrix proteins directly. The dynamic reciprocal communication between cells and the ECM plays a fundamental roll in tissue development, homeostasis, and wound healing.

  15. Review: cornification, morphogenesis and evolution of feathers.

    PubMed

    Alibardi, Lorenzo

    2017-05-01

    Feathers are corneous microramifications of variable complexity derived from the morphogenesis of barb ridges. Histological and ultrastructural analyses on developing and regenerating feathers clarify the three-dimensional organization of cells in barb ridges. Feather cells derive from folds of the embryonic epithelium of feather germs from which barb/barbule cells and supportive cells organize in a branching structure. The following degeneration of supportive cells allows the separation of barbule cells which are made of corneous beta-proteins and of lower amounts of intermediate filament (IF)(alpha) keratins, histidine-rich proteins, and corneous proteins of the epidermal differentiation complex. The specific protein association gives rise to a corneous material with specific biomechanic properties in barbules, rami, rachis, or calamus. During the evolution of different feather types, a large expansion of the genome coding for corneous feather beta-proteins occurred and formed 3-4-nm-thick filaments through a different mechanism from that of 8-10 nm IF keratins. In the chick, over 130 genes mainly localized in chromosomes 27 and 25 encode feather corneous beta-proteins of 10-12 kDa containing 97-105 amino acids. About 35 genes localized in chromosome 25 code for scale proteins (14-16 kDa made of 122-146 amino acids), claws and beak proteins (14-17 kDa proteins of 134-164 amino acids). Feather morphogenesis is periodically re-activated to produce replacement feathers, and multiple feather types can result from the interactions of epidermal and dermal tissues. The review shows schematic models explaining the translation of the morphogenesis of barb ridges present in the follicle into the three-dimensional shape of the main types of branched or un-branched feathers such as plumulaceous, pennaceous, filoplumes, and bristles. The temporal pattern of formation of barb ridges in different feather types and the molecular control from the dermal papilla through

  16. Head segmentation in vertebrates

    PubMed Central

    Kuratani, Shigeru; Schilling, Thomas

    2008-01-01

    Classic theories of vertebrate head segmentation clearly exemplify the idealistic nature of comparative embryology prior to the 20th century. Comparative embryology aimed at recognizing the basic, primary structure that is shared by all vertebrates, either as an archetype or an ancestral developmental pattern. Modern evolutionary developmental (Evo-Devo) studies are also based on comparison, and therefore have a tendency to reduce complex embryonic anatomy into overly simplified patterns. Here again, a basic segmental plan for the head has been sought among chordates. We convened a symposium that brought together leading researchers dealing with this problem, in a number of different evolutionary and developmental contexts. Here we give an overview of the outcome and the status of the field in this modern era of Evo-Devo. We emphasize the fact that the head segmentation problem is not fully resolved, and we discuss new directions in the search for hints for a way out of this maze. PMID:20607135

  17. Viruses of lower vertebrates.

    PubMed

    Essbauer, S; Ahne, W

    2001-08-01

    Viruses of lower vertebrates recently became a field of interest to the public due to increasing epizootics and economic losses of poikilothermic animals. These were reported worldwide from both wildlife and collections of aquatic poikilothermic animals. Several RNA and DNA viruses infecting fish, amphibians and reptiles have been studied intensively during the last 20 years. Many of these viruses induce diseases resulting in important economic losses of lower vertebrates, especially in fish aquaculture. In addition, some of the DNA viruses seem to be emerging pathogens involved in the worldwide decline in wildlife. Irido-, herpes- and polyomavirus infections may be involved in the reduction in the numbers of endangered amphibian and reptile species. In this context the knowledge of several important RNA viruses such as orthomyxo-, paramyxo-, rhabdo-, retro-, corona-, calici-, toga-, picorna-, noda-, reo- and birnaviruses, and DNA viruses such as parvo-, irido-, herpes-, adeno-, polyoma- and poxviruses, is described in this review.

  18. Regional variation in morphology of vertebral centra and intervertebral joints in striped bass, Morone saxatilis.

    PubMed

    Nowroozi, B N; Harper, C J; De Kegel, B; Adriaens, D; Brainerd, E L

    2012-04-01

    The vertebral column of fishes has traditionally been divided into just two distinct regions, abdominal and caudal. Recently, however, developmental, morphological, and mechanical investigations have brought this traditional regionalization scheme into question. Alternative regionalization schema advocate the division of the abdominal vertebrae into cervical, abdominal, and in some cases, transitional regions. Here, we investigate regional variation at the level of the vertebrae and intervertebral joint (IVJ) tissues in the striped bass, Morone saxatilis. We use gross dissection, histology, and polarized light imaging to quantify vertebral height, width, length, IVJ length, IVJ tissue volume and cross-sectional area, and vertical septum fiber populations, and angles of insertion. Our results reveal regional differences between the first four (most rostral) abdominal vertebrae and IVJs and the next six abdominal vertebrae and IVJs, supporting the recognition of a distinct cervical region. We found significant variation in vertebral length, width, and height from cranial to caudal. In addition, we see a significant decline in the volume of notochordal cells and the cross-sectional area of the fibrous sheath from cranial to caudal. Further, polarized light imaging revealed four distinct fiber populations within the vertical septum in the cervical and abdominal regions in contrast with just one fiber population found in the caudal region. Measurement of the insertion angles of these fiber populations revealed significant differences between the cervical and abdominal regions. Differences in vertebral, IVJ, and vertical septum morphology all predict greater range of motion and decreased stiffness in the caudal region of the fish compared with the cervical and abdominal regions.

  19. Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties

    PubMed Central

    Vyas, Neha; Walvekar, Ankita; Tate, Dhananjay; Lakshmanan, Vairavan; Bansal, Dhiru; Cicero, Alessandra Lo; Raposo, Graca; Palakodeti, Dasaradhi; Dhawan, Jyotsna

    2014-01-01

    Hedgehog (Hh) is a secreted morphogen that elicits differentiation and patterning in developing tissues. Multiple proposed mechanisms to regulate Hh dispersion includes lipoprotein particles and exosomes. Here we report that vertebrate Sonic Hedgehog (Shh) is secreted on two types of extracellular-vesicles/exosomes, from human cell lines and primary chick notochord cells. Although largely overlapping in size as estimated from electron micrographs, the two exosomal fractions exhibited distinct protein and RNA composition. We have probed the functional properties of these vesicles using cell-based assays of Hh-elicited gene expression. Our results suggest that while both Shh-containing exo-vesicular fractions can activate an ectopic Gli-luciferase construct, only exosomes co-expressing Integrins can activate endogenous Shh target genes HNF3β and Olig2 during the differentiation of mouse ES cells to ventral neuronal progenitors. Taken together, our results demonstrate that primary vertebrate cells secrete Shh in distinct vesicular forms, and support a model where packaging of Shh along with other signaling proteins such as Integrins on exosomes modulates target gene activation. The existence of distinct classes of Shh-containing exosomes also suggests a previously unappreciated complexity for fine-tuning of Shh-mediated gradients and pattern formation. PMID:25483805

  20. Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties.

    PubMed

    Vyas, Neha; Walvekar, Ankita; Tate, Dhananjay; Lakshmanan, Vairavan; Bansal, Dhiru; Lo Cicero, Alessandra; Raposo, Graca; Palakodeti, Dasaradhi; Dhawan, Jyotsna

    2014-12-08

    Hedgehog (Hh) is a secreted morphogen that elicits differentiation and patterning in developing tissues. Multiple proposed mechanisms to regulate Hh dispersion includes lipoprotein particles and exosomes. Here we report that vertebrate Sonic Hedgehog (Shh) is secreted on two types of extracellular-vesicles/exosomes, from human cell lines and primary chick notochord cells. Although largely overlapping in size as estimated from electron micrographs, the two exosomal fractions exhibited distinct protein and RNA composition. We have probed the functional properties of these vesicles using cell-based assays of Hh-elicited gene expression. Our results suggest that while both Shh-containing exo-vesicular fractions can activate an ectopic Gli-luciferase construct, only exosomes co-expressing Integrins can activate endogenous Shh target genes HNF3β and Olig2 during the differentiation of mouse ES cells to ventral neuronal progenitors. Taken together, our results demonstrate that primary vertebrate cells secrete Shh in distinct vesicular forms, and support a model where packaging of Shh along with other signaling proteins such as Integrins on exosomes modulates target gene activation. The existence of distinct classes of Shh-containing exosomes also suggests a previously unappreciated complexity for fine-tuning of Shh-mediated gradients and pattern formation.

  1. 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

  2. Development and evolution of the vertebrate primary mouth.

    PubMed

    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

  3. 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

  4. 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

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

    PubMed

    Martin, Adam C; Goldstein, Bob

    2014-05-01

    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.

  6. A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition

    PubMed Central

    Ohazama, Atsushi; Blackburn, James; Porntaveetus, Thantrira; Ota, Masato S.; Choi, Hong Y.; Johnson, Eric B.; Myers, Philip; Oommen, Shelly; Eto, Kazuhiro; Kessler, John A.; Kondo, Takashi; Fraser, Gareth J.; Streelman, J. Todd; Pardiñas, Ulyses F. J.; Tucker, Abigail S.; Ortiz, Pablo E.; Charles, Cyril; Viriot, Laurent; Herz, Joachim; Sharpe, Paul T.

    2009-01-01

    Changes in tooth shape have played a major role in vertebrate evolution with modification of dentition allowing an organism to adapt to new feeding strategies. The current view is that molar teeth evolved from simple conical teeth, similar to canines, by progressive addition of extra “cones” to form progressively complex multicuspid crowns. Mammalian incisors, however, are neither conical nor multicuspid, and their evolution is unclear. We show that hypomorphic mutation of a cell surface receptor, Lrp4, which modulates multiple signaling pathways, produces incisors with grooved enamel surfaces that exhibit the same molecular characteristics as the tips of molar cusps. Mice with a null mutation of Lrp4 develop extra cusps on molars and have incisors that exhibit clear molar-like cusp and root morphologies. Molecular analysis identifies misregulation of Shh and Bmp signaling in the mutant incisors and suggests an uncoupling of the processes of tooth shape determination and morphogenesis. Incisors thus possess a developmentally suppressed, cuspid crown-like morphogenesis program similar to that in molars that is revealed by loss of Lrp4 activity. Several mammalian species naturally possess multicuspid incisors, suggesting that mammals have the capacity to form multicuspid teeth regardless of location in the oral jaw. Localized loss of enamel may thus have been an intermediary step in the evolution of cusps, both of which use Lrp4-mediated signaling. PMID:20018657

  7. A role for suppressed incisor cuspal morphogenesis in the evolution of mammalian heterodont dentition.

    PubMed

    Ohazama, Atsushi; Blackburn, James; Porntaveetus, Thantrira; Ota, Masato S; Choi, Hong Y; Johnson, Eric B; Myers, Philip; Oommen, Shelly; Eto, Kazuhiro; Kessler, John A; Kondo, Takashi; Fraser, Gareth J; Streelman, J Todd; Pardiñas, Ulyses F J; Tucker, Abigail S; Ortiz, Pablo E; Charles, Cyril; Viriot, Laurent; Herz, Joachim; Sharpe, Paul T

    2010-01-05

    Changes in tooth shape have played a major role in vertebrate evolution with modification of dentition allowing an organism to adapt to new feeding strategies. The current view is that molar teeth evolved from simple conical teeth, similar to canines, by progressive addition of extra "cones" to form progressively complex multicuspid crowns. Mammalian incisors, however, are neither conical nor multicuspid, and their evolution is unclear. We show that hypomorphic mutation of a cell surface receptor, Lrp4, which modulates multiple signaling pathways, produces incisors with grooved enamel surfaces that exhibit the same molecular characteristics as the tips of molar cusps. Mice with a null mutation of Lrp4 develop extra cusps on molars and have incisors that exhibit clear molar-like cusp and root morphologies. Molecular analysis identifies misregulation of Shh and Bmp signaling in the mutant incisors and suggests an uncoupling of the processes of tooth shape determination and morphogenesis. Incisors thus possess a developmentally suppressed, cuspid crown-like morphogenesis program similar to that in molars that is revealed by loss of Lrp4 activity. Several mammalian species naturally possess multicuspid incisors, suggesting that mammals have the capacity to form multicuspid teeth regardless of location in the oral jaw. Localized loss of enamel may thus have been an intermediary step in the evolution of cusps, both of which use Lrp4-mediated signaling.

  8. Role of the Polycystins in Cell Migration, Polarity, and Tissue Morphogenesis

    PubMed Central

    Nigro, Elisa Agnese; Castelli, Maddalena; Boletta, Alessandra

    2015-01-01

    Cystic kidney diseases (CKD) is a class of disorders characterized by ciliary dysfunction and, therefore, belonging to the ciliopathies. The prototype CKD is autosomal dominant polycystic kidney disease (ADPKD), whose mutated genes encode for two membrane-bound proteins, polycystin-1 (PC-1) and polycystin-2 (PC-2), of unknown function. Recent studies on CKD-associated genes identified new mechanisms of morphogenesis that are central for establishment and maintenance of proper renal tubular diameter. During embryonic development in the mouse and lower vertebrates a convergent-extension (CE)-like mechanism based on planar cell polarity (PCP) and cellular intercalation is involved in “sculpting” the tubules into a narrow and elongated shape. Once the appropriate diameter is established, further elongation occurs through oriented cell division (OCD). The polycystins (PCs) regulate some of these essential processes. In this review we summarize recent work on the role of PCs in regulating cell migration, the cytoskeleton, and front-rear polarity. These important properties are essential for proper morphogenesis of the renal tubules and the lymphatic vessels. We highlight here several open questions and controversies. Finally, we try to outline some of the next steps required to study these processes and their relevance in physiological and pathological conditions. PMID:26529018

  9. The Role of Sdf-1α signaling in Xenopus laevis somite morphogenesis.

    PubMed

    Leal, Marisa A; Fickel, Sarah R; Sabillo, Armbien; Ramirez, Julio; Vergara, Hernando Martínez; Nave, Ceazar; Saw, Daniel; Domingo, Carmen R

    2014-04-01

    Stromal derived factor-1α (sdf-1α), a chemoattractant chemokine, plays a major role in tumor growth, angiogenesis, metastasis, and in embryogenesis. The sdf-1α signaling pathway has also been shown to be important for somite rotation in zebrafish (Hollway et al., 2007). Given the known similarities and differences between zebrafish and Xenopus laevis somitogenesis, we sought to determine whether the role of sdf-1α is conserved in Xenopus laevis. Using a morpholino approach, we demonstrate that knockdown of sdf-1α or its receptor, cxcr4, leads to a significant disruption in somite rotation and myotome alignment. We further show that depletion of sdf-1α or cxcr4 leads to the near absence of β-dystroglycan and laminin expression at the intersomitic boundaries. Finally, knockdown of sdf-1α decreases the level of activated RhoA, a small GTPase known to regulate cell shape and movement. Our results show that sdf-1α signaling regulates somite cell migration, rotation, and myotome alignment by directly or indirectly regulating dystroglycan expression and RhoA activation. These findings support the conservation of sdf-1α signaling in vertebrate somite morphogenesis; however, the precise mechanism by which this signaling pathway influences somite morphogenesis is different between the fish and the frog. Copyright © 2013 Wiley Periodicals, Inc.

  10. The role of Sdf-1α signaling in Xenopus laevis somite morphogenesis

    PubMed Central

    Leal, Marisa A.; Fickel, Sarah R.; Sabillo, Armbien; Ramirez, Julio; Vergara, Hernando Martínez; Nave, Ceazar; Saw, Daniel; Domingo, Carmen R.

    2014-01-01

    Background Stromal derived factor-1α (sdf-1α), a chemoattractant chemokine, plays a major role in tumor growth, angiogenesis, metastasis and in embryogenesis. The sdf-1α signaling pathway has also been shown to be important for somite rotation in zebrafish (Hollway, et al 2007). Given the known similarities and differences between zebrafish and Xenopus laevis somitogenesis, we sought to determine whether the role of sdf-1α is conserved in Xenopus laevis. Results Using a morpholino approach, we demonstrate that knockdown of sdf-1α or its receptor, cxcr4, leads to a significant disruption in somite rotation and myotome alignment. We further show that depletion of sdf-1α or cxcr4 leads to the near absence of β-dystroglycan and laminin expression at the intersomitic boundaries. Finally, knockdown of sdf-1α decreases the level of activated RhoA, a small GTPase known to regulate cell shape and movement. Conclusion Our results show that sdf-1α signaling regulates somite cell migration, rotation and myotome alignment by directly or indirectly regulating dystroglycan expression and RhoA activation. These findings support the conservation of sdf-1α signaling in vertebrate somite morphogenesis; however, the precise mechanism by which this signaling pathway influences somite morphogenesis is different between the fish and the frog. PMID:24357195

  11. Wls-mediated Wnts differentially regulate distal limb patterning and tissue morphogenesis.

    PubMed

    Zhu, Xuming; Zhu, Huang; Zhang, Lingling; Huang, Sixia; Cao, Jingjing; Ma, Gang; Feng, Guoying; He, Lin; Yang, Yingzi; Guo, Xizhi

    2012-05-15

    Wnt proteins are diffusible morphogens that play multiple roles during vertebrate limb development. However, the complexity of Wnt signaling cascades and their overlapping expression prevent us from dissecting their function in limb patterning and tissue morphogenesis. Depletion of the Wntless (Wls) gene, which is required for the secretion of various Wnts, makes it possible to genetically dissect the overall effect of Wnts in limb development. In this study, the Wls gene was conditionally depleted in limb mesenchyme and ectoderm. The loss of mesenchymal Wls prevented the differentiation of distal mesenchyme and arrested limb outgrowth, most likely by affecting Wnt5a function. Meanwhile, the deletion of ectodermal Wls resulted in agenesis of distal limb tissue and premature regression of the distal mesenchyme. These observations suggested that Wnts from the two germ layers differentially regulate the pool of undifferentiated distal limb mesenchyme cells. Cellular behavior analysis revealed that ectodermal Wnts sustain mesenchymal cell proliferation and survival in a manner distinct from Fgf. Ectodermal Wnts were also shown for the first time to be essential for distal tendon/ligament induction, myoblast migration and dermis formation in the limb. These findings provide a comprehensive view of the role of Wnts in limb patterning and tissue morphogenesis.

  12. Ernest Everett Just, Johannes Holtfreter, and the Origin of Certain Concepts in Embryo Morphogenesis

    PubMed Central

    BYRNES, W. MALCOLM

    2012-01-01

    SUMMARY Ernest E. Just (1883–1941) is best known for his discovery of the “wave of negativity” that sweeps of the sea urchin egg during fertilization, and his elucidation of what are known as the fast and slow blocks to polyspermy. Just’s contemporary Johannes Holtfreter (1901–1992) is known for his pioneering work in amphibian morphogenesis, which helped to lay the foundation for modern vertebrate developmental biology. This paper, after briefly describing the life and scientific contributions of Just, argues that his work and ideas strongly influenced two of the concepts for which Holtfreter is best known: tissue affinity and autoneuralization (or autoinduction). Specifically, this paper argues that, first, Just’s experiments demonstrating developmental stage-specific changes in the adhesiveness of the blastomeres of cleavage embryos helped lay the foundation for Holtfreter’s concept of tissue affinity and, second, Just’s notion of the intrinsic irritability of the egg cell, which is evident in experimental parthenogenesis, strongly informed Holtfreter’s concept of the nonspecific induction of neural tissue formation in amphibian gastrula ectoderm explants, a phenomenon known as auto-induction. Acknowledgment of these contributions by Just in no way diminishes the importance of Holtfreter’s groundbreaking work. It does, however, extend the impact of Just’s work into the area of embryo morphogenesis. It connects Just to Holtfreter and positions his work as an antecedent to embryo research that continues to this day. PMID:19610071

  13. Ca2+ dynamics in zebrafish morphogenesis

    PubMed Central

    Tsutsui, Kenta; Ogawa, Tomohisa

    2017-01-01

    Intracellular calcium ion (Ca2+) signaling is heavily involved in development, as illustrated by the use of a number of Ca2+ indicators. However, continuous Ca2+ patterns during morphogenesis have not yet been studied using fluorescence resonance energy transfer to track the Ca2+ sensor. In the present study, we monitored Ca2+ levels during zebrafish morphogenesis and differentiation with yellow cameleon, YC2.12. Our results show not only clear changes in Ca2+ levels but also continuous Ca2+ patterns at 24 hpf and later periods for the first time. Serial Ca2+dynamics during early pharyngula period (Prim-5-20; 24–33 hpf) was successfully observed with cameleon, which have not reported anywhere yet. In fact, high Ca2+ level occurred concurrently with hindbrain development in segmentation and pharyngula periods. Ca2+ patterns in the late gastrula through segmentation periods which were obtained with cameleon, were similar to those obtained previously with other Ca2+sensor. Our results suggested that the use of various Ca2+ sensors may lead to novel findings in studies of Ca2+ dynamics. We hope that these results will prove valuable for further research in Ca2+ signaling. PMID:28133572

  14. Homophilic Dscam interactions control complex dendrite morphogenesis

    PubMed Central

    Hughes, Michael E.; Bortnick, Rachel; Tsubouchi, Asako; Bäumer, Philipp; Kondo, Masahiro; Uemura, Tadashi; Schmucker, Dietmar

    2007-01-01

    Summary The morphogenesis of complex dendritic fields requires highly specific patterning and dendrite-dendrite recognition mechanisms. Alternative splicing of the Drosophila cell surface receptor Dscam results in up to 38,016 different receptor isoforms and in vitro binding studies suggested that sequence variability in immunoglobulin-like ecto-domains determines the specificity of strictly homophilic interactions. We report that diverse Dscam receptors play an important role in controlling cell-intrinsic aspects of dendrite guidance. We examined the function of Dscam during morphogenesis of dendrite arborization neurons (“da” neurons) and found that loss of Dscam in single neurons causes abnormal dendritic fasciculation and a strong increase in self-crossing of dendritic branches of da neurons. Restriction of dendritic fields of neighboring class III neurons appeared intact in Dscam deficient neurons suggesting that dendritic self-avoidance but not hetero-neuronal tiling may depend on Dscam function. Over-expression of the same Dscam isoforms in two da neurons with normally overlapping dendritic fields forced a spatial segregation of the two dendritic fields. Taken together, our results suggest that dendritic branches of all four classes of da neurons use isoform-specific homophilic interactions of Dscam to ensure minimal overlap of dendrites. The large pool of Dscam’s extracellular recognition domains may allow the same ‘core’ repulsion mechanism to be used in every da neuron without interfering with hetero-neuronal interactions. PMID:17481395

  15. Morphogenesis in giant-celled algae.

    PubMed

    Mine, Ichiro; Menzel, Diedrik; Okuda, Kazuo

    2008-01-01

    The giant-celled algae, which consist of cells reaching millimeters in size, some even centimeters, exhibit unique cell architecture and physiological characteristics. Their cells display a variety of morphogenetic phenomena, that is, growth, division, differentiation, and reproductive cell formation, as well as wound-healing responses. Studies using immunofluorescence microscopy and pharmacological approaches have shown that microtubules and/or actin filaments are involved in many of these events through the generation of intracellular movement of cell components or entire protoplasmic contents and the spatial control of cell activities in specific areas of the giant cells. A number of environmental factors including physical stimuli, such as light and gravity, invoke localized but also generalized cellular reactions. These have been extensively investigated to understand the regulation of morphogenesis, in particular addressing cytoskeletal and endomembrane dynamics, electrophysiological elements affecting ion fluxes, and the synthesis and mechanical properties of the cell wall. Some of the regulatory pathways involve signal transduction and hormonal control, as in other organisms. The giant unicellular green alga Acetabularia, which has proven its usefulness as an experimental model in early amputation/grafting experiments, will potentially once again serve as a useful model organism for studying the role of gene expression in orchestrating cellular morphogenesis.

  16. A Unifying Theory of Branching Morphogenesis.

    PubMed

    Hannezo, Edouard; Scheele, Colinda L G J; Moad, Mohammad; Drogo, Nicholas; Heer, Rakesh; Sampogna, Rosemary V; van Rheenen, Jacco; Simons, Benjamin D

    2017-09-21

    The morphogenesis of branched organs remains a subject of abiding interest. Although much is known about the underlying signaling pathways, it remains unclear how macroscopic features of branched organs, including their size, network topology, and spatial patterning, are encoded. Here, we show that, in mouse mammary gland, kidney, and human prostate, these features can be explained quantitatively within a single unifying framework of branching and annihilating random walks. Based on quantitative analyses of large-scale organ reconstructions and proliferation kinetics measurements, we propose that morphogenesis follows from the proliferative activity of equipotent tips that stochastically branch and randomly explore their environment but compete neutrally for space, becoming proliferatively inactive when in proximity with neighboring ducts. These results show that complex branched epithelial structures develop as a self-organized process, reliant upon a strikingly simple but generic rule, without recourse to a rigid and deterministic sequence of genetically programmed events. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. The ‘Tully monster’ is a vertebrate

    NASA Astrophysics Data System (ADS)

    McCoy, Victoria E.; Saupe, Erin E.; Lamsdell, James C.; Tarhan, Lidya G.; McMahon, Sean; Lidgard, Scott; Mayer, Paul; Whalen, Christopher D.; Soriano, Carmen; Finney, Lydia; Vogt, Stefan; Clark, Elizabeth G.; Anderson, Ross P.; Petermann, Holger; Locatelli, Emma R.; Briggs, Derek E. G.

    2016-04-01

    Problematic fossils, extinct taxa of enigmatic morphology that cannot be assigned to a known major group, were once a major issue in palaeontology. A long-favoured solution to the ‘problem of the problematica’, particularly the ‘weird wonders’ of the Cambrian Burgess Shale, was to consider them representatives of extinct phyla. A combination of new evidence and modern approaches to phylogenetic analysis has now resolved the affinities of most of these forms. Perhaps the most notable exception is Tullimonstrum gregarium, popularly known as the Tully monster, a large soft-bodied organism from the late Carboniferous Mazon Creek biota (approximately 309-307 million years ago) of Illinois, USA, which was designated the official state fossil of Illinois in 1989. Its phylogenetic position has remained uncertain and it has been compared with nemerteans, polychaetes, gastropods, conodonts, and the stem arthropod Opabinia. Here we review the morphology of Tullimonstrum based on an analysis of more than 1,200 specimens. We find that the anterior proboscis ends in a buccal apparatus containing teeth, the eyes project laterally on a long rigid bar, and the elongate segmented body bears a caudal fin with dorsal and ventral lobes. We describe new evidence for a notochord, cartilaginous arcualia, gill pouches, articulations within the proboscis, and multiple tooth rows adjacent to the mouth. This combination of characters, supported by phylogenetic analysis, identifies Tullimonstrum as a vertebrate, and places it on the stem lineage to lampreys (Petromyzontida). In addition to increasing the known morphological disparity of extinct lampreys, a chordate affinity for T. gregarium resolves the nature of a soft-bodied fossil which has been debated for more than 50 years.

  18. 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

  19. Multifaceted roles of Furry proteins in invertebrates and vertebrates.

    PubMed

    Nagai, Tomoaki; Mizuno, Kensaku

    2014-03-01

    Furry (Fry) is a large protein that is evolutionarily conserved from yeast to human. Fry and its orthologues in invertebrates (termed Tao3p in budding yeast, Mor2p in fission yeast, Sax-2 in nematode and Fry in fruit fly) genetically and physically interact with nuclear Dbf2-related (NDR) kinases (termed Cbk1p in budding yeast, Orb6p in fission yeast, Sax-1 in nematode and Trc in fruitfly), and function as activators or scaffolds of these kinases. Fry-NDR kinase signals are implicated in the control of polarized cell growth and morphogenesis in yeast, neurite outgrowth in nematode, and epidermal morphogenesis and dendritic tiling in fruit fly. Recent studies revealed that mammalian Fry is a microtubule-associated protein that is involved in the control of chromosome alignment, spindle organization and Polo-like kinase-1 activation in mitosis, and promotes microtubule acetylation in mitotic spindles via inhibiting the tubulin deacetylase Sirtuin 2. Here, we review current knowledge about the diverse cellular functions and regulation of Fry proteins in invertebrates and vertebrates.

  20. What's new in vertebral cementoplasty?

    PubMed Central

    Guarnieri, Gianluigi; Giurazza, Francesco; Manfrè, Luigi

    2016-01-01

    Vertebral cementoplasty is a well-known mini-invasive treatment to obtain pain relief in patients affected by vertebral porotic fractures, primary or secondary spine lesions and spine trauma through intrametameric cement injection. Two major categories of treatment are included within the term vertebral cementoplasty: the first is vertebroplasty in which a simple cement injection in the vertebral body is performed; the second is assisted technique in which a device is positioned inside the metamer before the cement injection to restore vertebral height and allow a better cement distribution, reducing the kyphotic deformity of the spine, trying to obtain an almost normal spine biomechanics. We will describe the most advanced techniques and indications of vertebral cementoplasty, having recently expanded the field of applications to not only patients with porotic fractures but also spine tumours and trauma. PMID:26728798

  1. 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

  2. Molecular and cellular mechanisms of dendritic morphogenesis

    PubMed Central

    Gao, Fen-Biao

    2008-01-01

    Summary Dendrites exhibit unique cell-type specific branching patterns and targeting specificity that are critically important for neuronal function and connectivity. Recent evidence indicates that highly complex transcriptional regulatory networks dictate various aspects of dendritic outgrowth, branching, and routing. In addition to other intrinsic molecular pathways such as membrane protein trafficking, interactions between neighboring dendritic branches also contribute to the final specification of dendritic morphology. Nonredundant coverage by dendrites of same type of neurons, known as tiling, requires the actions of the Tricornered/Furry (Sax-1/Sax-2) signaling pathway. However, the dendrites of a neuron do not cross over each other, a process called self-avoidance that is mediated by Down’s syndrome cell adhesion molecule (Dscam). Those exciting findings have enhanced significantly our understanding of dendritic morphogenesis and revealed the magnitude of complexity in the underlying molecular regulatory networks. PMID:17933513

  3. Control of morphogenesis in Geodermatophilus: ultrastructural studies.

    PubMed

    Ishiguro, E E; Wolfe, R S

    1970-10-01

    Geodermatophilus grows in two major forms, a nonmotile irregularly shaped aggregate of coccoid cells (C-form) and a motile budding rod (R-form). Morphogenesis can be controlled by an unidentified factor in Tryptose which is required for maintenance of the organism in the C-form and for differentiation of the R-form to the C-form. Morphogenetic events occur synchronously in the described system. Ultrastructural studies show that the major difference between C- and R-forms is in cells envelope structure. R-form cell walls consist of two layers, an inner transparent membranous layer (10 to 12.5 nm thick) and an outer dense diffuse layer (7.5 to 10 nm). In addition to these layers, the C-form has a thick fibrous layer (30 nm) over the dense layer. This layer appears to be a cementing substance which holds the coccoid cells together.

  4. Control of Morphogenesis in Geodermatophilus: Ultrastructural Studies

    PubMed Central

    Ishiguro, Edward E.; Wolfe, R. S.

    1970-01-01

    Geodermatophilus grows in two major forms, a nonmotile irregularly shaped aggregate of coccoid cells (C-form) and a motile budding rod (R-form). Morphogenesis can be controlled by an unidentified factor in Tryptose which is required for maintenance of the organism in the C-form and for differentiation of the R-form to the C-form. Morphogenetic events occur synchronously in the described system. Ultrastructural studies show that the major difference between C- and R-forms is in cells envelope structure. R-form cell walls consist of two layers, an inner transparent membranous layer (10 to 12.5 nm thick) and an outer dense diffuse layer (7.5 to 10 nm). In addition to these layers, the C-form has a thick fibrous layer (30 nm) over the dense layer. This layer appears to be a cementing substance which holds the coccoid cells together. Images PMID:5473909

  5. Morphogenesis in Belousov-Zhabotinsky microdroplets

    NASA Astrophysics Data System (ADS)

    Li, Ning; Tompkins, Nathan; Girabawe, Camille; Epstein, Irving; Fraden, Seth; Brandeis/Mrsec Team

    2013-03-01

    We present experimental evidence for the six cases Alan Turing predicted using linear stability analysis in his 1952 paper ``The chemical basis of morphogenesis'' in our reaction diffusion system. Our experimental system consists of a microfluidically generated microemulsion consisting of Ru(bipy)3 catalyzed light sensitive BZ aqueous droplets which are diffusively coupled through oil gaps. We observed that some droplets grow and others shrink due to the unequal consumption of chemicals in the droplets which leads to an osmotic pressure change, as Turing predicted in his paper. The initial and boundary conditions of our system were controlled by programmable illumination via the light sensitive catalyst Ru(bipy)3. Simulation and linear stability analysis were performed and compared with the experiments. Funded by MRSEC.

  6. Diagnosing vertebral fractures: missed opportunities.

    PubMed

    Borges, João Lindolfo Cunha; Maia, Julianne Lira; Silva, Renata Faria; Lewiecki, Edward Michael

    2015-01-01

    Vertebral fractures are the single most common type of osteoporotic fracture. Postmenopausal women are at increased risk for osteoporotic vertebral fractures compared with women of childbearing age. Vertebral fractures are associated with an increase in morbidity, mortality, and high risk of a subsequent vertebral fracture, regardless of bone mineral density. Despite the common occurrence and serious consequences of vertebral fractures, they are often unrecognized or misdiagnosed by radiologists. Moreover, vertebral fractures may be described by variable terminology that can confuse rather than enlighten referring physicians. We conducted a survey of spine X-ray reports from a group of postmenopausal women screened for participation in a study of osteoporosis at Centro de Pesquisa Clínica do Brasil. A descriptive analysis evaluated the variability of reports in 7 patients. Four independent general radiologists issued reports assessing vertebral fractures through a blinded analysis. The objective of this study was to evaluate for consistency in these reports. The analysis found marked variability in the diagnosis of vertebral fractures and the terminology used to describe them. In community medical practices, such variability could lead to differences in the management of patients with osteoporosis, with the potential for undertreatment or overtreatment depending on clinical circumstances. Accurate and unambiguous reporting of vertebral fractures is likely to be associated with improved clinical outcomes. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

  7. Cellular Potts modeling of complex multicellular behaviors in tissue morphogenesis.

    PubMed

    Hirashima, Tsuyoshi; Rens, Elisabeth G; Merks, Roeland M H

    2017-06-01

    Mathematical modeling is an essential approach for the understanding of complex multicellular behaviors in tissue morphogenesis. Here, we review the cellular Potts model (CPM; also known as the Glazier-Graner-Hogeweg model), an effective computational modeling framework. We discuss its usability for modeling complex developmental phenomena by examining four fundamental examples of tissue morphogenesis: (i) cell sorting, (ii) cyst formation, (iii) tube morphogenesis in kidney development, and (iv) blood vessel formation. The review provides an introduction for biologists for starting simulation analysis using the CPM framework. © 2017 Japanese Society of Developmental Biologists.

  8. Palate Morphogenesis: Current Understanding and Future Directions

    PubMed Central

    Greene, Robert M.; Pisano, M. Michele

    2011-01-01

    In the past, most scientists conducted their inquiries of nature via inductivism, the patient accumulation of “pieces of information” in the pious hope that the sum of the parts would clarify the whole. Increasingly, modern biology employs the tools of bioinformatics and systems biology in attempts to reveal the “big picture.” Most successful laboratories engaged in the pursuit of the secrets of embryonic development, particularly those whose research focus is craniofacial development, pursue a middle road where research efforts embrace, rather than abandon, what some have called the “pedestrian” qualities of inductivism, while increasingly employing modern data mining technologies. The secondary palate has provided an excellent paradigm that has enabled examination of a wide variety of developmental processes. Examination of cellular signal transduction, as it directs embryogenesis, has proven exceptionally revealing with regard to clarification of the “facts” of palatal ontogeny—at least the facts as we currently understand them. Herein, we review the most basic fundamentals of orofacial embryology and discuss how functioning of TGFβ, BMP, Shh, and Wnt signal transduction pathways contributes to palatal morphogenesis. Our current understanding of palate medial edge epithelial differentiation is also examined. We conclude with a discussion of how the rapidly expanding field of epigenetics, particularly regulation of gene expression by miRNAs and DNA methylation, is critical to control of cell and tissue differentiation, and how examination of these epigenetic processes has already begun to provide a better understanding of, and greater appreciation for, the complexities of palatal morphogenesis. PMID:20544696

  9. Key steps in the morphogenesis of a cranial placode in an invertebrate chordate, the tunicate Ciona savignyi.

    PubMed

    Kourakis, Matthew J; Newman-Smith, Erin; Smith, William C

    2010-04-01

    Tunicates and vertebrates share a common ancestor that possessed cranial neurogenic placodes, thickenings in embryonic head epidermis giving rise to sensory structures. Though orthology assignments between vertebrate and tunicate placodes are not entirely resolved, vertebrate otic placodes and tunicate atrial siphon primordia are thought to be homologous based on morphology and position, gene expression, and a common signaling requirement during induction. Here, we probe key points in the morphogenesis of the tunicate atrial siphon. We show that the siphon primordium arises within a non-dividing field of lateral-dorsal epidermis. The initial steps of atrial primordium invagination are similar to otic placode invagination, but a placode-derived vesicle is never observed as for the otic vesicle of vertebrates. Rather, confocal imaging reveals an atrial opening through juvenile stages and beyond. We inject a photoactivatable lineage tracer to show that the early atrial siphon of the metamorphic juvenile, including its aperture and lining, derives from cells of the atrial placode itself. Finally, we perturb the routing of the gut to the left atrium by laser ablation and pharmacology to show that this adaptation to a sessile lifestyle depends on left-right patterning mechanisms present in the free-swimming chordate ancestor.

  10. Spermatogenesis in nonmammalian vertebrates.

    PubMed

    Pudney, J

    1995-12-15

    Spermatogenesis appears to be a fairly conserved process throughout the vertebrate series. Thus, spermatogonia develop into spermatocytes that undergo meiosis to produce spermatids which enter spermiogenesis where they undergo a morphological transformation into spermatozoa. There is, however, variation amongst the vertebrates in how germ cell development and maturation is accomplished. This difference can be broadly divided into two distinct patterns, one present in anamniotes (fish, amphibia) and the other in amniotes (reptiles, birds, mammals). For anamniotes, spermatogenesis occurs in spermatocysts (cysts) which for most species develop within seminiferous lobules. Cysts are produced when a Sertoli cell becomes associated with a primary spermatogonium. Mitotic divisions of the primary spermatogonium produce a cohort of secondary spermatogonia that are enclosed by the Sertoli cell which forms the wall of the cyst. With spermatogenic progression a clone of isogeneic spermatozoa is produced which are released, by rupture of the cyst, into the lumen of the seminiferous lobule. Following spermiation, the Sertoli cell degenerates. For anamniotes, therefore, there is no permanent germinal epithelium since spermatocysts have to be replaced during successive breeding seasons. By contrast, spermatogenesis in amniotes does not occur in cysts but in seminiferous tubules that possess a permanent population of Sertoli cells and spermatogonia which act as a germ cell reservoir for succeeding bouts of spermatogenic activity. There is, in general, a greater variation in the organization of the testis and pattern of spermatogenesis in the anamniotes compared to amniotes. This is primarily due to the fact there is more reproductive diversity in anamniotes ranging from a relatively unspecialized condition where gametes are simply released into the aqueous environment to highly specialized strategies involving internal fertilization. These differences are obviously reflected in the

  11. The human vertebral column at the end of the embryonic period proper. 2. The occipitocervical region.

    PubMed Central

    O'Rahilly, R; Müller, F; Meyer, D B

    1983-01-01

    The present investigation of the cervical region of the vertebral column at eight post-ovulatory weeks is the first such study based on precise reconstructions of staged embryos. At the end of the embryonic period proper, a typical vertebra is a U-shaped piece of cartilage characterized by spina bifida occulta. The notochord ascends through the centra and leaves the dens to enter the basal plate of the skull. The median column of the axis comprises three parts (designated X, Y, Z) which persist well into the fetal period. They are related to the first, second and third cervical nerves, respectively. Part X may project into the foramen magnum and form an occipito-axial joint. Part Z appears to be the centrum of the axis. The articular columns of the cervical vertebrae are twofold, as in the adult: an anterior (atlanto-occipital and atlanto-axial) and a posterior (from the lower aspect of the axis downwards). Alar and transverse ligaments are present. Cavitation is not found in the embryonic period in either the atlanto-occipital or zygapophysial joints, and is generally not present in the median atlanto-axial joint either. Most of the transverse processes exhibit anterior and posterior tubercles. An 'intertubercular lamella' may or may not be present, i.e. the foramina transversaria are being formed around the vertebral artery. The spinal ganglia are generally partly in the vertebral canal and partly on the neural arches, medial to the articular processes. During the fetal period, the articular processes shift to a coronal position and this alteration appears to be associated with a corresponding change in the location of the spinal ganglia. Images Fig. 4 Fig. 7 PMID:6833119

  12. Microtubule-dependent cell morphogenesis in the fission yeast.

    PubMed

    Martin, Sophie G

    2009-09-01

    In many systems, microtubules contribute spatial information to cell morphogenesis, for instance in cell migration and division. In rod-shaped fission yeast cells, microtubules control cell morphogenesis by transporting polarity factors, namely the Tea1-Tea4 complex, to cell tips. This complex then recruits the DYRK kinase Pom1 to cell ends. Interestingly, recent work has shown that these proteins also provide long-range spatial cues to position the division site in the middle of the cell and temporal signals to coordinate cell length with the cell cycle. Here I review how these microtubule-associated proteins form polar morphogenesis centers that control and integrate both spatial and temporal aspects of cell morphogenesis.

  13. Chemical ecology of vertebrate carrion

    USDA-ARS?s Scientific Manuscript database

    Vertebrate carrion is a nutrient-rich, ephemeral resource that is utilized by many different organisms ranging from vertebrate and invertebrate scavengers to microbes. The organisms that consume carrion play an important ecological role, as decomposition is vital to ecosystem function. Without the...

  14. Opportunistic Identification of Vertebral Fractures.

    PubMed

    Adams, Judith E

    2016-01-01

    Vertebral fractures are powerful predictors of future fracture, so, their identification is important to ensure that patients are commenced on appropriate bone protective or bone-enhancing therapy. Risk factors (e.g., low bone mineral density and increasing age) and symptoms (back pain, loss of height) may herald the presence of vertebral fractures, which are usually confirmed by performing spinal radiographs or, increasingly, using vertebral fracture assessment with dual-energy X-ray absorptiometry scanners. However, a large number (30% or more) of vertebral fractures are asymptomatic and do not come to clinical attention. There is, therefore, scope for opportunistic (fortuitous) identification of vertebral fractures from various imaging modalities (radiographs, computed tomography, magnetic resonance imaging, and radionuclide scans) performed for other clinical indications and which include the spine in the field of view, with midline sagittal reformatted images from computed tomography having the greatest potential for such opportunistic detection. Numerous studies confirm this potential for identification but consistently find underreporting of vertebral fractures. So, a valuable opportunity to improve the management of patients at increased risk of future fracture is being squandered. Educational training programs for all clinicians and constant reiteration, stressing the importance of the accurate and clear reporting of vertebral fractures ("you only see what you look for"), can improve the situation, and automated computer-aided diagnostic tools also show promise to solve the problem of this underreporting of vertebral fractures. Copyright © 2016. Published by Elsevier Inc.

  15. Vestigial-like-2b (VITO-1b) and Tead-3a (Tef-5a) expression in zebrafish skeletal muscle, brain and notochord.

    PubMed

    Mann, Christopher J; Osborn, Daniel P S; Hughes, Simon M

    2007-10-01

    The vestigial gene has been shown to control skeletal muscle formation in Drosophila and the related Vestigial-like 2 (Vgl-2) protein plays a similar role in mice. Vgl-family proteins are thought to regulate tissue-specific gene expression by binding to members of the broadly expressed Scalloped/Tef/TEAD transcription factor family. Zebrafish have at least four Vgl genes, including two Vgl-2s, and at least three TEAD genes, including two Tead3s. We describe the cloning and expression of one member from each family in the zebrafish. A novel gene, vgl-2b, with closest homology to mouse and human vgl-2, is expressed transiently in nascent notochord and in muscle fibres as they undergo terminal differentiation during somitogenesis. Muscle cells also express a TEAD-3 homologue, a possible partner of Vgl-2b, during myoblast differentiation and early fibre assembly. Tead-3a is also expressed in rhombomeres, eye and epiphysis regions.

  16. Vestigial-like-2b (VITO-1b) and Tead-3a (Tef-5a) expression in zebrafish skeletal muscle, brain and notochord

    PubMed Central

    Mann, Christopher J.; Osborn, Daniel P.S.; Hughes, Simon M.

    2012-01-01

    The vestigial gene has been shown to control skeletal muscle formation in Drosophila and the related Vestigial-like 2 (Vgl-2) protein plays a similar role in mice. Vgl-family proteins are thought to regulate tissue-specific gene expression by binding to members of the broadly expressed Scalloped/Tef/TEAD transcription factor family. Zebrafish have at least four Vgl genes, including two Vgl-2s, and at least three TEAD genes, including two Tead3s. We describe the cloning and expression of one member from each family in the zebrafish. A novel gene, vgl-2b, with closest homology to mouse and human vgl-2, is expressed transiently in nascent notochord and in muscle fibres as they undergo terminal differentiation during somitogenesis. Muscle cells also express a TEAD-3 homologue, a possible partner of Vgl-2b, during myoblast differentiation and early fibre assembly. Tead3a is also expressed in rhombomeres, eye and epiphysis regions. PMID:17916448

  17. 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.

  18. 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.

  19. Vertebrate head development: segmentation, novelties, and homology.

    PubMed

    Olsson, Lennart; Ericsson, Rolf; Cerny, Robert

    2005-11-01

    Vertebrate head development is a classical topic lately invigorated by methodological as well as conceptual advances. In contrast to the classical segmentalist views going back to idealistic morphology, the head is now seen not as simply an extension of the trunk, but as a structure patterned by different mechanisms and tissues. Whereas the trunk paraxial mesoderm imposes its segmental pattern on adjacent tissues such as the neural crest derivatives, in the head the neural crest cells carry pattern information needed for proper morphogenesis of mesodermal derivatives, such as the cranial muscles. Neural crest cells make connective tissue components which attach the muscle fiber to the skeletal elements. These crest cells take their origin from the same visceral arch as the muscle cells, even when the skeletal elements to which the muscle attaches are from another arch. The neural crest itself receives important patterning influences from the pharyngeal endoderm. The origin of jaws can be seen as an exaptation in which a heterotopic shift of the expression domains of regulatory genes was a necessary step that enabled this key innovation. The jaws are patterned by Dlx genes expressed in a nested pattern along the proximo-distal axis, analogous to the anterior-posterior specification governed by Hox genes. Knocking out Dlx 5 and 6 transforms the lower jaw homeotically into an upper jaw. New data indicate that both upper and lower jaw cartilages are derived from one, common anlage traditionally labelled the "mandibular" condensation, and that the "maxillary" condensation gives rise to other structures such as the trabecula. We propose that the main contribution from evolutionary developmental biology to solving homology questions lies in deepening our biological understanding of characters and character states.

  20. Comparative anatomy: all vertebrates do have vertebrae.

    PubMed

    Janvier, Philippe

    2011-09-13

    In contrast to lampreys and jawed vertebrates, hagfishes were thought to lack vertebrae. Now, long overlooked vertebral rudiments have been analysed in hagfish, suggesting that vertebrae existed in the last common ancestor of all vertebrates.

  1. 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.

  2. Planar Cell Polarity Signaling in Collective Cell Movements During Morphogenesis and Disease

    PubMed Central

    Muñoz-Soriano, Verónica; Belacortu, Yaiza; Paricio, Nuria

    2012-01-01

    Collective and directed cell movements are crucial for diverse developmental processes in the animal kingdom, but they are also involved in wound repair and disease. During these processes groups of cells are oriented within the tissue plane, which is referred to as planar cell polarity (PCP). This requires a tight regulation that is in part conducted by the PCP pathway. Although this pathway was initially characterized in flies, subsequent studies in vertebrates revealed a set of conserved core factors but also effector molecules and signal modulators, which build the fundamental PCP machinery. The PCP pathway in Drosophila regulates several developmental processes involving collective cell movements such as border cell migration during oogenesis, ommatidial rotation during eye development, and embryonic dorsal closure. During vertebrate embryogenesis, PCP signaling also controls collective and directed cell movements including convergent extension during gastrulation, neural tube closure, neural crest cell migration, or heart morphogenesis. Similarly, PCP signaling is linked to processes such as wound repair, and cancer invasion and metastasis in adults. As a consequence, disruption of PCP signaling leads to pathological conditions. In this review, we will summarize recent findings about the role of PCP signaling in collective cell movements in flies and vertebrates. In addition, we will focus on how studies in Drosophila have been relevant to our understanding of the PCP molecular machinery and will describe several developmental defects and human disorders in which PCP signaling is compromised. Therefore, new discoveries about the contribution of this pathway to collective cell movements could provide new potential diagnostic and therapeutic targets for these disorders. PMID:23730201

  3. 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

  4. Mechanical growth and morphogenesis of seashells.

    PubMed

    Moulton, D E; Goriely, A; Chirat, R

    2012-10-21

    Seashells grow through the local deposition of mass along the aperture. Many mathematical descriptions of the shapes of shells have been provided over the years, and the basic logarithmic coiling seen in mollusks can be simulated with few parameters. However, the developmental mechanisms underlying shell coiling are largely not understood and the ubiquitous presence of ornamentation such as ribs, tubercles, or spines presents yet another level of difficulty. Here we develop a general model for shell growth based entirely on the local geometry and mechanics of the aperture and mantle. This local description enables us to efficiently describe both arbitrary growth velocities and the evolution of the shell aperture itself. We demonstrate how most shells can be simulated within this framework. We then turn to the mechanics underlying the shell morphogenesis, and develop models for the evolution of the aperture. We demonstrate that the elastic response of the mantle during shell deposition provides a natural mechanism for the formation of three-dimensional ornamentation in shells.

  5. Multiscale information modelling for heart morphogenesis

    NASA Astrophysics Data System (ADS)

    Abdulla, T.; Imms, R.; Schleich, J. M.; Summers, R.

    2010-07-01

    Science is made feasible by the adoption of common systems of units. As research has become more data intensive, especially in the biomedical domain, it requires the adoption of a common system of information models, to make explicit the relationship between one set of data and another, regardless of format. This is being realised through the OBO Foundry to develop a suite of reference ontologies, and NCBO Bioportal to provide services to integrate biomedical resources and functionality to visualise and create mappings between ontology terms. Biomedical experts tend to be focused at one level of spatial scale, be it biochemistry, cell biology, or anatomy. Likewise, the ontologies they use tend to be focused at a particular level of scale. There is increasing interest in a multiscale systems approach, which attempts to integrate between different levels of scale to gain understanding of emergent effects. This is a return to physiological medicine with a computational emphasis, exemplified by the worldwide Physiome initiative, and the European Union funded Network of Excellence in the Virtual Physiological Human. However, little work has been done on how information modelling itself may be tailored to a multiscale systems approach. We demonstrate how this can be done for the complex process of heart morphogenesis, which requires multiscale understanding in both time and spatial domains. Such an effort enables the integration of multiscale metrology.

  6. Morphogenesis of the human lacrimal gland

    PubMed Central

    de la Cuadra-Blanco, C; Peces-Peña, M D; Mérida-Velasco, J R

    2003-01-01

    The aim of this study was to determine the main stages of the lacrimal gland's developmental process in humans and to establish its precise morphogenetic timetable. Its onset is generally assumed to take place at O'Rahilly's stage 21, arising from an epithelial thickening of the superior extreme of the temporary conjunctival fornix. However, the present study points to a prior stage in the process: the presence of epithelial–mesenchymal changes in embryos at O'Rahilly's stage 19. The study was performed using light microscopy on serial sections of 37 human specimens: 23 embryos and 14 fetuses ranging from 15 to 137 mm crown–rump length (7–116 weeks of development). Three stages in lacrimal gland morphogenesis were identified: (1) the presumptive glandular stage, O'Rahilly's stages 19–20, characterized by a thickening of the superior fornix epithelium together with surrounding mesenchymal condensation; (2) the bud stage, generally assumed to be the first manifestation of glandular origin, characterized initially by the appearance of nodular formations in the region of the superior conjunctival fornix and concluding with the appearance of lumina within the epithelial buds; and (3) the glandular maturity stage, weeks 9–16, the period in which the gland begins to take on the morphology of adulthood. PMID:14635806

  7. Mechanical feedback stabilizes budding yeast morphogenesis

    NASA Astrophysics Data System (ADS)

    Banavar, Samhita; Trogdon, Michael; Petzold, Linda; Campas, Otger

    Walled cells have the ability to remodel their shape while sustaining an internal turgor pressure that can reach values up to 10 atmospheres. This requires a tight and simultaneous regulation of cell wall assembly and mechanochemistry, but the underlying mechanisms by which this is achieved remain unclear. Using the growth of mating projections in budding yeast (S. cerevisiae) as a motivating example, we have developed a theoretical description that couples the mechanics of cell wall expansion and assembly via a mechanical feedback. In the absence of a mechanical feedback, cell morphogenesis is inherently unstable. The presence of a mechanical feedback stabilizes changes in cell shape and growth, and provides a mechanism to prevent cell lysis in a wide range of conditions. We solve for the dynamics of the system and obtain the different dynamical regimes. In particular, we show that several parameters affect the stability of growth, including the strength of mechanical feedback in the system. Finally, we compare our results to existing experimental data.

  8. FGF10 signaling controls stomach morphogenesis

    PubMed Central

    Nyeng, Pia; Norgaard, Gitte Anker; Kobberup, Sune; Jensen, Jan

    2007-01-01

    Maintenance of progenitor cell properties in development is required for proper organogenesis of most organs, including those derived from the endoderm. FGF10 has been shown to play a role in both lung and pancreatic development. Here we find that FGF10 signaling controls stomach progenitor maintenance, morphogenesis and cellular differentiation. Through a characterization of the initiation of terminal differentiation of the three major gastric regions in the mouse, forestomach, corpus and antrum, we first describe the existence of a “secondary transition” event occurring in mouse stomach between E15.5-E16.5. This includes the formation of terminally differentiated squamous cells, parietal, chief a nd gastric endocrine cells from a pre-patterned gastric progenitor epithelium. Expression analysis of both FGF and Notch signaling components suggested a role of these networks in such progenitors, which was tested through ectopically expressing FGF10 in the developing posterior stomach. These data provide evidence that gastric gland specification and progenitor cell maintenance is controlled by FGF10. The glandular proliferative niche was disrupted in pPDX-FGF10FLAG mice leading to aberrant gland formation, and endocrine and parietal cell differentiation was attenuated. These effects were paralleled by changes in Hes1, Shh, and Wnt6 expression, suggesting that FGF10 acts in concert with multiple morphogenetic signaling systems during gastric development. PMID:17196193

  9. Genetic regulation of dentate gyrus morphogenesis.

    PubMed

    Li, Guangnan; Pleasure, Samuel J

    2007-01-01

    The dentate gyrus is one of the small number of forebrain areas that have continued adult neurogenesis. During development the dentate gyrus acquires the capacity for neurogenesis by generating a new neurogenic stem cell niche at the border between the hilus and dentate granule cell layer. This is in distinction to the other prominent zone of continued neurogenesis in the subventricular zone where neurons are born in a structure directly descended from the mid-gestation subventricular zone. The ability to generate this newly formed dentate neurogenic niche is controlled by the action of a number of genes during prenatal and early postnatal development that regulate the fate, survival, migration, expansion, and differentiation of the cellular components of the dentate neurogenic niche. In this review, we provide an updated framework discussing the molecular steps and genes involved in these early stages of dentate gyrus formation. We previously described a molecular framework for dentate gyrus morphogenesis that can be associated with specific gene defects (Li, G., Pleasure, S.J. (2005). Dev. Neurosci., 27, 93-99), and here we add additional recently described molecular players and discuss this framework.

  10. Epithelial dynamics of pancreatic branching morphogenesis

    PubMed Central

    Villasenor, Alethia; Chong, Diana C.; Henkemeyer, Mark; Cleaver, Ondine

    2010-01-01

    The mammalian pancreas is a highly branched gland, essential for both digestion and glucose homeostasis. Pancreatic branching, however, is poorly understood, both at the ultrastructural and cellular levels. In this article, we characterize the morphogenesis of pancreatic branches, from gross anatomy to the dynamics of their epithelial organization. We identify trends in pancreatic branch morphology and introduce a novel mechanism for branch formation, which involves transient epithelial stratification and partial loss of cell polarity, changes in cell shape and cell rearrangements, de novo tubulogenesis and epithelial tubule remodeling. In contrast to the classical epithelial budding and tube extension observed in other organs, a pancreatic branch takes shape as a multi-lumen tubular plexus coordinately extends and remodels into a ramifying, single-lumen ductal system. Moreover, our studies identify a role for EphB signaling in epithelial remodeling during pancreatic branching. Overall, these results illustrate distinct, step-wise cellular mechanisms by which pancreatic epithelium shapes itself to create a functional branching organ. PMID:21098570

  11. Heparin activates Wnt signaling for neuronal morphogenesis.

    PubMed

    Colombres, Marcela; Henríquez, Juan Pablo; Reig, Germán F; Scheu, Jessica; Calderón, Rosario; Alvarez, Alejandra; Brandan, Enrique; Inestrosa, Nibaldo C

    2008-09-01

    Wnt factors are secreted ligands that affect different aspects of the nervous system behavior like neurodevelopment, synaptogenesis and neurodegeneration. In different model systems, Wnt signaling has been demonstrated to be regulated by heparan sulfate proteoglycans (HSPGs). Whether HSPGs modulate Wnt signaling in the context of neuronal behavior is currently unknown. Here we demonstrate that activation of Wnt signaling with the endogenous ligand Wnt-7a results in an increased of neurite outgrowth in the neuroblastoma N2a cell line. Interestingly, heparin induces glycogen synthase kinase-3beta (GSK-3beta) inhibition, beta-catenin stabilization and morphological differentiation in both N2a cells and in rat primary hippocampal neuronal cultures. We also show that heparin modulates Wnt-3a-induced stabilization of beta-catenin. Several extracellular matrix and membrane-attached HSPGs were found to be expressed in both in vitro neuronal models. Changes in the expression of specific HSPGs were observed upon differentiation of N2a cells. Taken together, our findings suggest that HSPGs may modulate canonical Wnt signaling for neuronal morphogenesis.

  12. Early morphogenesis of heterodont dentition in minipigs.

    PubMed

    Stembírek, Jan; Buchtová, Marcela; Král, Tomáš; Matalová, Eva; Lozanoff, Scott; Míšek, Ivan

    2010-12-01

    The minipig provides an excellent experimental model for tooth morphogenesis because its diphyodont and heterodont dentition resemble that of humans. However, little information is available on the processes of tooth development in the pig. The purpose of this study was to classify the early stages of odontogenesis in minipigs from the initiation of deciduous dentition to the late bell stage when the successional dental lamina begins to develop. To analyze the initiation of teeth anlagens and the structural changes of dental lamina, a three-dimensional (3D) analysis was performed. At the earliest stage, 3D reconstruction revealed a continuous dental lamina along the length of the jaw. Later, the dental lamina exhibited remarkable differences in depth, and the interdental lamina was shorter. The dental lamina grew into the mesenchyme in the lingual direction, and its inclined growth was underlined by asymmetrical cell proliferation. After the primary tooth germ reached the late bell stage, the dental lamina began to disintegrate and fragmentize. Some cells disappeared during the process of lamina degradation, while others remained in small islands known as epithelial pearls. The minipig can therefore, inter alia, be used as a model organism to study the fate of epithelial pearls from their initiation to their contribution to pathological structures, primarily because of the clinical significance of these epithelial rests. © 2010 Eur J Oral Sci.

  13. SUMO enhances vestigial function during wing morphogenesis.

    PubMed

    Takanaka, Yoko; Courey, Albert J

    2005-10-01

    The conjugation of the ubiquitin-like protein SUMO to lysine side chains plays widespread roles in the regulation of nuclear protein function. Since little information is available about the roles of SUMO in development, we have screened a collection of chromosomal deficiencies to identify developmental processes regulated by SUMO. We found that flies heterozygous for a deficiency uncovering vestigial (vg) and mutations in any of several genes encoding components of the SUMO conjugation machinery exhibit severe wing notching. This phenotype is due to an interaction between sumo and vg since it is suppressed by expression of Vg from a transgene, and is also observed in flies doubly heterozygous for vg hypomorphic alleles and sumo. In addition, the ability of Vg to direct the formation of ectopic wings when misexpressed in the eye field is enhanced by simultaneous misexpression of SUMO. In S2 cell transient transfection assays, overexpression of SUMO and the SUMO conjugating enzyme Ubc9, but not a catalytically inactive form of Ubc9, results in sumoylation of Vg and augments the activation of a Vg-responsive reporter. These findings are consistent with the idea that sumoylation stimulates Vg function during wing morphogenesis.

  14. Ultrastructural morphogenesis of salmonid alphavirus 1.

    PubMed

    Herath, T K; Ferguson, H W; Thompson, K D; Adams, A; Richards, R H

    2012-11-01

    Studies on the ultrastructural morphogenesis of viruses give an insight into how the host cell mechanisms are utilized for new virion synthesis. A time course examining salmonid alphavirus 1 (SAV 1) assembly was performed by culturing the virus on Chinook salmon embryo cells (CHSE-214). Different stages of viral replication were observed under electron microscopy. Virus-like particles were observed inside membrane-bound vesicles as early as 1 h following contact of the virus with the cells. Membrane-dependent replication complexes were observed in the cytoplasm of the cells, with spherules found at the periphery of late endosome-like vacuoles. The use of intracellular membranes for RNA replication is similar to other positive-sense single-stranded RNA (+ssRNA) viruses. The number of Golgi apparatus and associated vacuoles characterized by 'fuzzy'-coated membranes was greater in virus-infected cells. The mature enveloped virions started to bud out from the cells at approximately 24 h post-infection. These observations suggest that the pathway used by SAV 1 for the generation of new virus particles in vitro is comparable to viral replication observed with mammalian alphaviruses but with some interesting differences.

  15. 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.

  16. Evolution of the vertebrate epididymis.

    PubMed

    Jones, R C

    1998-01-01

    This review examines the structure and function of the extratesticular sperm ducts of vertebrates in terms of their evolutionary development and adaptive significance. The primitive extratesticular duct system of Chondrichthyes is described as an example of the vertebrate archetype. Adaptations of the duct system in higher vertebrates have involved a loss of some structures and specialization of others. The duct system probably evolved as a homeostatic mechanism to facilitate fertilization and some embryological development under conditions protected from the external environment. However, it is argued that the ducts also play an important role in the competition between males to achieve paternity. In vertebrates that practise internal fertilization the ducts are involved in post-testicular maturation and storage of spermatozoa. The biological significance of post-testicular sperm maturation has not been resolved. By contrast, sperm storage is essential in most male vertebrates because of the slow rate of spermatogenesis, particularly in ectotherms. Sperm storage is also important in the competition between males for paternity as it enables a male to mate a 'partner' a number of times during an oestrus in order to reduce the prospect of being cuckolded by another male. The extent of sperm maturation and storage in the epididymis of particular vertebrates depends on the relative roles of the testis and its extragonadal ducts in the competition between males for paternity. These roles depend on a number of factors, including allometric limitations to testis size, metabolic rate and the development of endothermy, and the reproductive strategy of females of the species.

  17. 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.

  18. Heterotypic Control of Basement Membrane Dynamics During Branching Morphogenesis

    PubMed Central

    Nelson, Deirdre A.; Larsen, Melinda

    2015-01-01

    Many mammalian organs undergo branching morphogenesis to create highly arborized structures with maximized surface area for specialized organ function. Cooperative cell-cell and cell-matrix adhesions that sculpt the emerging tissue architecture are guided by dynamic basement membranes. Properties of the basement membrane are reciprocally controlled by the interacting epithelial and mesenchymal cell populations. Here we discuss how basement membrane remodeling is required for branching morphogenesis to regulate cell-matrix and cell-cell adhesions that are required for cell patterning during morphogenesis and how basement membrane impacts morphogenesis by stimulation of cell patterning, force generation, and mechanotransduction. We suggest that in addition to creating mature epithelial architecture, remodeling of the epithelial basement membrane during branching morphogenesis is also essential to promote maturation of the stromal mesenchyme to create mature organ structure. Recapitulation of developmental cell-matrix and cell-cell interactions are of critical importance in tissue engineering and regeneration strategies that seek to restore organ function. PMID:25527075

  19. Specificity protein 7 is not essential for tooth morphogenesis.

    PubMed

    Clarke, John C; Bae, Ji-Myung; Adhami, Mitra; Rashid, Harunur; Chen, Haiyan; Napierala, Dobrawa; Gutierrez, Soraya E; Sinha, Krishna; Crombrugghe, Benoit de; Javed, Amjad

    2014-08-01

    Tooth formation is a multifaceted process involving numerous interactions between oral epithelium and neural crest derived ecto-mesenchyme from morphogenesis to cyto-differentiation. The precise molecular regulator that drives the cyto-differentiation and dynamic cross-talk between the two cell types has yet to be fully understood. Runx2 along with its downstream target Sp7 are essential transcription factors for development of the mineralizing cell types. Global knockout of the Runx2 gene results in an arrest of tooth morphogenesis at the late bud stage. Like Runx2, Sp7-null mutants exhibit peri-natal lethality and are completely devoid of alveolar bone. However, the role of Sp7 in tooth development remains elusive. Here, we report the effects of Sp7 deletion on tooth formation. Surprisingly, tooth morphogenesis progresses normally until the mid bell stage in Sp7-homozygous mutants. Incisors and multi-cusped first and second molars were noted in both littermates. Thus, formation of alveolar bone is not a prerequisite for tooth morphogenesis. Tooth organs of Sp7-null however, were significantly smaller in size when compared to WT. Differentiation of both ameloblasts and odontoblasts was disrupted in Sp7-null mice. Only premature and disorganized ameloblasts and odontoblasts were noted in mutant mice. These data indicate that Sp7 is not required for tooth morphogenesis but is obligatory for the functional maturation of both ameloblasts and odontoblasts.

  20. Specificity protein 7 is not essential for tooth morphogenesis

    PubMed Central

    Clarke, John C.; Bae, Ji-Myung; Adhami, Mitra; Rashid, Harunur; Chen, Haiyan; Napierala, Dobrawa; Gutierrez, Soraya E.; Sinha, Krishna; de Crombrugghe, Benoit; Javed, Amjad

    2014-01-01

    Tooth formation is a multifaceted process involving numerous interactions between oral epithelium and neural crest derived ecto-mesenchyme from morphogenesis to cytodifferentiation. The precise molecular regulator that drives the cyto-differentiation and dynamic cross-talk between the two cell types has yet to be fully understood. Runx2 along with its downstream target Sp7 are essential transcription factors for development of the mineralizing cell types. Global knockout of the Runx2 gene results in an arrest of tooth morphogenesis at the late bud stage. Like Runx2, Sp7-null mutants exhibit peri-natal lethality and are completely devoid of alveolar bone. However, the role of Sp7 in tooth development remains elusive. Here, we report the effects of Sp7 deletion on tooth formation. Surprisingly, tooth morphogenesis progresses normally until the mid bell stage in Sp7-homozygous mutants. Incisors and multi-cusped first and second molars were noted in both littermates. Thus, formation of alveolar bone is not a prerequisite for tooth morphogenesis. Tooth organs of Sp7-null however, were significantly smaller in size when compared to WT. Differentiation of both ameloblasts and odontoblasts was disrupted in Sp7-null mice. Only premature and disorganized ameloblasts and odontoblasts were noted in mutant mice. These data indicate that Sp7 is not required for tooth morphogenesis but is obligatory for the functional maturation of both ameloblasts and odontoblasts. PMID:25158188

  1. Quantitative methods to study epithelial morphogenesis and polarity.

    PubMed

    Aigouy, B; Collinet, C; Merkel, M; Sagner, A

    2017-01-01

    Morphogenesis of an epithelial tissue emerges from the behavior of its constituent cells, including changes in shape, rearrangements, and divisions. In many instances the directionality of these cellular events is controlled by the polarized distribution of specific molecular components. In recent years, our understanding of morphogenesis and polarity highly benefited from advances in genetics, microscopy, and image analysis. They now make it possible to measure cellular dynamics and polarity with unprecedented precision for entire tissues throughout their development. Here we review recent approaches to visualize and measure cell polarity and tissue morphogenesis. The chapter is organized like an experiment. We first discuss the choice of cell and polarity reporters and describe the use of mosaics to reveal hidden cell polarities or local morphogenetic events. Then, we outline application-specific advantages and disadvantages of different microscopy techniques and image projection algorithms. Next, we present methods to extract cell outlines to measure cell polarity and detect cellular events underlying morphogenesis. Finally, we bridge scales by presenting approaches to quantify the specific contribution of each cellular event to global tissue deformation. Taken together, we provide an in-depth description of available tools and theoretical concepts to quantitatively study cell polarity and tissue morphogenesis over multiple scales.

  2. Myosin II Dynamics during Embryo Morphogenesis

    NASA Astrophysics Data System (ADS)

    Kasza, Karen

    2013-03-01

    During embryonic morphogenesis, the myosin II motor protein generates forces that help to shape tissues, organs, and the overall body form. In one dramatic example in the Drosophila melanogaster embryo, the epithelial tissue that will give rise to the body of the adult animal elongates more than two-fold along the head-to-tail axis in less than an hour. This elongation is accomplished primarily through directional rearrangements of cells within the plane of the tissue. Just prior to elongation, polarized assemblies of myosin II accumulate perpendicular to the elongation axis. The contractile forces generated by myosin activity orient cell movements along a common axis, promoting local cell rearrangements that contribute to global tissue elongation. The molecular and mechanical mechanisms by which myosin drives this massive change in embryo shape are poorly understood. To investigate these mechanisms, we generated a collection of transgenic flies expressing variants of myosin II with altered motor function and regulation. We found that variants that are predicted to have increased myosin activity cause defects in tissue elongation. Using biophysical approaches, we found that these myosin variants also have decreased turnover dynamics within cells. To explore the mechanisms by which molecular-level myosin dynamics are translated into tissue-level elongation, we are using time-lapse confocal imaging to observe cell movements in embryos with altered myosin activity. We are utilizing computational approaches to quantify the dynamics and directionality of myosin localization and cell rearrangements. These studies will help elucidate how myosin-generated forces control cell movements within tissues. This work is in collaboration with J. Zallen at the Sloan-Kettering Institute.

  3. Ultrastructure and morphogenesis of human immunodeficiency virus.

    PubMed

    Nakai, M; Goto, T

    1996-08-01

    The ultrastructure and morphogenesis of human immunodeficiency virus (HIV) were elucidated by observation with several techniques including immunoelectron microscopy and cryo-microscopy. The virus particle consists of an envelope, a core and matrix. The virus particles were observed extracellularly as having one of three profiles: (1) a centric or an eccentric electron-dense core, (2) rod-shaped electron-dense core, and (3) doughnut-shaped. HIV-1 particles in the hydrated state were observed by high resolution electron cryo-microscopy to be globular, and the lipid membrane was clearly resolved as a bilayer. Many projections around the circumference were seen to be knob-like. The shapes and sizes of the projections, especially head parts, were found to vary in each projection. By isolation with Nonidet P40 and glutaraldehyde, HIV-1 cores were confirmed to consist of p24 protein by immunogold labeling. When the virus enters the cell, two entry modes were found: membrane fusion and endocytosis. No structures resembling virus particles could be seen in the cytoplasm after viral entry. In HIV-1-infected cells, positive reactions by immuno-labeling suggest that HIV-1 Gag may be produced in membrane-bound structures and transported to the cell surface by cytoskeletons. Then a crescent electron-dense layer was first formed underneath the cell membrane. Finally, the virus particle was released from the cell surface. Several cell clones producing defective particles were isolated from MT-4/HIV-1 cells. Among them, doughnut-shaped or teardrop-shaped particles were seen to be produced in the extracellular space. In the doughnut-shaped particles, Gag p17 and p24 proteins faced each other against the inner electron dense ring, suggesting that the inner ring consists of a precursor Gag protein.

  4. Morphogenesis of simple leaves: regulation of leaf size and shape.

    PubMed

    Rodriguez, Ramiro E; Debernardi, Juan M; Palatnik, Javier F

    2014-01-01

    Plants produce new organs throughout their life span. Leaves first initiate as rod-like structures protruding from the shoot apical meristem, while they need to pass through different developmental stages to become the flat organ specialized in photosynthesis. Leaf morphogenesis is an active process regulated by many genes and pathways that can generate organs with a wide variety of sizes and shapes. Important differences in leaf architecture can be seen among different species, but also in single individuals. A key aspect of leaf morphogenesis is the precise control of cell proliferation. Modification or manipulation of this process may lead to leaves with different sizes and shapes, and changes in the organ margins and curvature. Many genes required for leaf development have been identified in Arabidopsis thaliana, and the mechanisms underlying leaf morphogenesis are starting to be unraveled at the molecular level. © 2013 Wiley Periodicals, Inc.

  5. Biomimetic evolutionary analysis: testing the adaptive value of vertebrate tail stiffness in autonomous swimming robots.

    PubMed

    Long, J H; Koob, T J; Irving, K; Combie, K; Engel, V; Livingston, N; Lammert, A; Schumacher, J

    2006-12-01

    For early vertebrates, a long-standing hypothesis is that vertebrae evolved as a locomotor adaptation, stiffening the body axis and enhancing swimming performance. While supported by biomechanical data, this hypothesis has not been tested using an evolutionary approach. We did so by extending biomimetic evolutionary analysis (BEA), which builds physical simulations of extinct systems, to include use of autonomous robots as proxies of early vertebrates competing in a forage navigation task. Modeled after free-swimming larvae of sea squirts (Chordata, Urochordata), three robotic tadpoles (;Tadros'), each with a propulsive tail bearing a biomimetic notochord of variable spring stiffness, k (N m(-1)), searched for, oriented to, and orbited in two dimensions around a light source. Within each of ten generations, we selected for increased swimming speed, U (m s(-1)) and decreased time to the light source, t (s), average distance from the source, R (m) and wobble maneuvering, W (rad s(-2)). In software simulation, we coded two quantitative trait loci (QTL) that determine k: bending modulus, E (Nm(-2)) and length, L (m). Both QTL were mutated during replication, independently assorted during meiosis and, as haploid gametes, entered into the gene pool in proportion to parental fitness. After random mating created three new diploid genotypes, we fabricated three new offspring tails. In the presence of both selection and chance events (mutation, genetic drift), the phenotypic means of this small population evolved. The classic hypothesis was supported in that k was positively correlated (r(2)=0.40) with navigational prowess, NP, the dimensionless ratio of U to the product of R, t and W. However, the plausible adaptive scenario, even in this simplified system, is more complex, since the remaining variance in NP was correlated with the residuals of R and U taken with respect to k, suggesting that changes in k alone are insufficient to explain the evolution of NP.

  6. Multiple forces contribute to cell sheet morphogenesis for dorsal closure in Drosophila.

    PubMed

    Kiehart, D P; Galbraith, C G; Edwards, K A; Rickoll, W L; Montague, R A

    2000-04-17

    The molecular and cellular bases of cell shape change and movement during morphogenesis and wound healing are of intense interest and are only beginning to be understood. Here, we investigate the forces responsible for morphogenesis during dorsal closure with three approaches. First, we use real-time and time-lapsed laser confocal microscopy to follow actin dynamics and document cell shape changes and tissue movements in living, unperturbed embryos. We label cells with a ubiquitously expressed transgene that encodes GFP fused to an autonomously folding actin binding fragment from fly moesin. Second, we use a biomechanical approach to examine the distribution of stiffness/tension during dorsal closure by following the response of the various tissues to cutting by an ultraviolet laser. We tested our previous model (Young, P.E., A.M. Richman, A.S. Ketchum, and D.P. Kiehart. 1993. Genes Dev. 7:29-41) that the leading edge of the lateral epidermis is a contractile purse-string that provides force for dorsal closure. We show that this structure is under tension and behaves as a supracellular purse-string, however, we provide evidence that it alone cannot account for the forces responsible for dorsal closure. In addition, we show that there is isotropic stiffness/tension in the amnioserosa and anisotropic stiffness/tension in the lateral epidermis. Tension in the amnioserosa may contribute force for dorsal closure, but tension in the lateral epidermis opposes it. Third, we examine the role of various tissues in dorsal closure by repeated ablation of cells in the amnioserosa and the leading edge of the lateral epidermis. Our data provide strong evidence that both tissues appear to contribute to normal dorsal closure in living embryos, but surprisingly, neither is absolutely required for dorsal closure. Finally, we establish that the Drosophila epidermis rapidly and reproducibly heals from both mechanical and ultraviolet laser wounds, even those delivered repeatedly. During

  7. Multiple Forces Contribute to Cell Sheet Morphogenesis for Dorsal Closure in Drosophila

    PubMed Central

    Kiehart, Daniel P.; Galbraith, Catherine G.; Edwards, Kevin A.; Rickoll, Wayne L.; Montague, Ruth A.

    2000-01-01

    The molecular and cellular bases of cell shape change and movement during morphogenesis and wound healing are of intense interest and are only beginning to be understood. Here, we investigate the forces responsible for morphogenesis during dorsal closure with three approaches. First, we use real-time and time-lapsed laser confocal microscopy to follow actin dynamics and document cell shape changes and tissue movements in living, unperturbed embryos. We label cells with a ubiquitously expressed transgene that encodes GFP fused to an autonomously folding actin binding fragment from fly moesin. Second, we use a biomechanical approach to examine the distribution of stiffness/tension during dorsal closure by following the response of the various tissues to cutting by an ultraviolet laser. We tested our previous model (Young, P.E., A.M. Richman, A.S. Ketchum, and D.P. Kiehart. 1993. Genes Dev. 7:29–41) that the leading edge of the lateral epidermis is a contractile purse-string that provides force for dorsal closure. We show that this structure is under tension and behaves as a supracellular purse-string, however, we provide evidence that it alone cannot account for the forces responsible for dorsal closure. In addition, we show that there is isotropic stiffness/tension in the amnioserosa and anisotropic stiffness/tension in the lateral epidermis. Tension in the amnioserosa may contribute force for dorsal closure, but tension in the lateral epidermis opposes it. Third, we examine the role of various tissues in dorsal closure by repeated ablation of cells in the amnioserosa and the leading edge of the lateral epidermis. Our data provide strong evidence that both tissues appear to contribute to normal dorsal closure in living embryos, but surprisingly, neither is absolutely required for dorsal closure. Finally, we establish that the Drosophila epidermis rapidly and reproducibly heals from both mechanical and ultraviolet laser wounds, even those delivered repeatedly

  8. Neuropilin-2 promotes branching morphogenesis in the mouse mammary gland.

    PubMed

    Goel, Hira Lal; Bae, Donggoo; Pursell, Bryan; Gouvin, Lindsey M; Lu, Shaolei; Mercurio, Arthur M

    2011-07-01

    Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing glands. A floxed NRP2 mouse was bred with an MMTV-Cre strain to generate a mammary gland-specific knockout of NRP2. MMTV-Cre;NRP2(loxP/loxP) mice exhibited significant defects in branching morphogenesis and ductal outgrowth compared with either littermate MMTV-Cre;NRP2(+/loxP) or MMTV-Cre mice. Mechanistic insight into this morphological defect was obtained from a mouse mammary cell line in which we observed that VEGF(165), an NRP2 ligand, induces branching morphogenesis in 3D cultures and that branching is dependent upon NRP2 as shown using shRNAs and a function-blocking antibody. Epithelial cells in the mouse mammary gland express VEGF, supporting the hypothesis that this NRP2 ligand contributes to mammary gland morphogenesis. Importantly, we demonstrate that VEGF and NRP2 activate focal adhesion kinase (FAK) and promote FAK-dependent branching morphogenesis in vitro. The significance of this mechanism is substantiated by our finding that FAK activation is diminished significantly in developing MMTV-Cre;NRP2(loxP/loxP) mammary glands compared with control glands. Together, our data reveal a VEGF/NRP2/FAK signaling axis that is important for branching morphogenesis and mammary gland development. In a broader context, our data support an emerging hypothesis that directional outgrowth and branching morphogenesis in a variety of tissues are influenced by signals that were identified initially for their role in axon guidance.

  9. Tissue-autonomous EcR functions are required for concurrent organ morphogenesis in the Drosophila embryo.

    PubMed

    Chavoshi, Tina M; Moussian, Bernard; Uv, Anne

    2010-01-01

    The insect hormone 20-hydroxy-ecdysone (20E) peaks at different stages during the life cycle. The hormone signal is commonly transmitted by a nuclear receptor consisting of the ecdysone receptor (EcR) and Ultraspiracle (Usp, orthologous to vertebrate RXR). EcR:Usp then initiate the expression of a series of gene regulators that help mediate biological responses to the hormone. Here, we investigated the embryonic ecdysone-signalling mechanism. The rise in 20E levels that occurs at mid-embryogenesis is required for major tissue movements to complete organ morphogenesis, but the functions of EcR and Usp during embryogenesis have remained unclear. We find that both EcR and Usp are essential for head involution, dorsal closure and tracheal and midgut morphogenesis, processes that also depend on 20E, arguing that embryonic 20E signals via EcR:Usp. We also show that EcR mediates the effects on organ morphogenesis in a tissue-autonomous manner and thus, that embryonic EcR functions are not fully reflected by the commonly used EcR activity assays. Finally, we show that embryonic 20E via EcR instructs the temporal and tissue-specific expression of four transcription factors that are needed for late embryogenesis and are common to the metamorphic 20E response. The results suggest that mid-embryonic EcR-activation imparts a level of gene regulation during embryonic organogenesis that has been largely overlooked, and possibly facilitates synchronized development of individual organs.

  10. Regional differences in neural crest morphogenesis

    PubMed Central

    Kuo, Bryan R

    2010-01-01

    Neural crest cells are pluripotent cells that emerge from the neural epithelium, migrate extensively and differentiate into numerous derivatives, including neurons, glial cells, pigment cells and connective tissue. Major questions concerning their morphogenesis include: (1) what establishes the pathways of migration? And (2), what controls the final destination and differentiation of various neural crest subpopulations? These questions will be addressed in this Review. Neural crest cells from the trunk level have been explored most extensively. Studies show that melanoblasts are specified shortly after they depart from the neural tube and this specification directs their migration into the dorsolateral pathway. We also consider other reports that present strong evidence for ventrally migrating neural crest cells being similarly fate restricted. Cranial neural crest cells have been less analyzed in this regard but the preponderance of evidence indicates that either the cranial neural crest cells are not fate-restricted or are extremely plastic in their developmental capability and that specification does not control pathfinding. Thus, the guidance mechanisms that control cranial neural crest migration and their behavior vary significantly from the trunk. The vagal neural crest arises at the axial level between the cranial and trunk neural crest and represents a transitional cell population between the head and trunk neural crest. We summarize new data to support this claim. In particular, we show that: (1) the vagal-level neural crest cells exhibit modest developmental bias; (2) there are differences in the migratory behavior between the anterior and the posterior vagal neural crest cells reminiscent of the cranial and the trunk neural crest, respectively and (3) the vagal neural crest cells take the dorsolateral pathway to the pharyngeal arches and the heart, but take the ventral pathway to the peripheral nervous system and the gut. However, these pathways are not

  11. A Mox homeobox gene in the gastropod mollusc Haliotis rufescens is differentially expressed during larval morphogenesis and metamorphosis.

    PubMed

    Degnan, B M; Degnan, S M; Fentenany, G; Morse, D E

    1997-07-07

    We have isolated a homeobox-containing cDNA from the gastropod mollusc Haliotis rufescens that is most similar to members of the Mox homeobox gene class. The derived Haliotis homeodomain sequence is 85% identical to mouse and frog Mox-2 homeodomains and 88.9% identical to the partial cnidarian cnox5-Hm homeodomain. Quantitative reverse transcription-polymerase chain reaction analysis of mRNA accumulation reveals that this gene, called HruMox, is expressed in the larva, but not in the early embryo. Transcripts are most prevalent during larval morphogenesis from trochophore to veliger. There are also transient increases in transcript prevalence 1 and 3 days after the intitiation of metamorphosis from veliger to juvenile. The identification of a molluscan Mox homeobox gene that is more closely related to vertebrate genes than other protostome (e.g. Drosophila) genes suggests the Mox class of homeobox genes may consist of several different families that have been conserved through evolution.

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

    PubMed

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

    2015-02-24

    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.

  13. Bone morphogenetic protein signaling promotes morphogenesis of blood vessels, wound epidermis, and actinotrichia during fin regeneration in zebrafish.

    PubMed

    Thorimbert, Valentine; König, Désirée; Marro, Jan; Ruggiero, Florence; Jaźwińska, Anna

    2015-10-01

    Zebrafish fin regeneration involves initial formation of the wound epidermis and the blastema, followed by tissue morphogenesis. The mechanisms coordinating differentiation of distinct tissues of the regenerate are poorly understood. Here, we applied pharmacologic and transgenic approaches to address the role of bone morphogenetic protein (BMP) signaling during fin restoration. To map the BMP transcriptional activity, we analyzed the expression of the evolutionarily conserved direct phospho-Smad1 target gene, id1, and its homologs id2a and id3. This analysis revealed the BMP activity in the distal blastema, wound epidermis, osteoblasts, and blood vessels of the regenerate. Blocking the BMP function with a selective chemical inhibitor of BMP type I receptors, DMH1, suppressed id1 and id3 expression and arrested regeneration after blastema formation. We identified several previously uncharacterized functions of BMP during fin regeneration. Specifically, BMP signaling is required for remodeling of plexus into structured blood vessels in the rapidly growing regenerate. It organizes the wound epithelium by triggering wnt5b expression and promoting Collagen XIV-A deposition into the basement membrane. BMP represents the first known signaling that induces actinotrichia formation in the regenerate. Our data reveal a multifaceted role of BMP for coordinated morphogenesis of distinct tissues during regeneration of a complex vertebrate appendage.

  14. The ubiquitin ligase PDZRN3 is required for vascular morphogenesis through Wnt/planar cell polarity signalling.

    PubMed

    Sewduth, Raj N; Jaspard-Vinassa, Béatrice; Peghaire, Claire; Guillabert, Aude; Franzl, Nathalie; Larrieu-Lahargue, Frederic; Moreau, Catherine; Fruttiger, Marcus; Dufourcq, Pascale; Couffinhal, Thierry; Duplàa, Cécile

    2014-09-08

    Development and stabilization of a vascular plexus requires the coordination of multiple signalling processes. Wnt planar cell polarity (PCP) signalling is critical in vertebrates for diverse morphogenesis events, which coordinate cell orientation within a tissue-specific plane. However, its functional role in vascular morphogenesis is not well understood. Here we identify PDZRN3, an ubiquitin ligase, and report that Pdzrn3 deficiency impairs embryonic angiogenic remodelling and postnatal retinal vascular patterning, with a loss of two-dimensional polarized orientation of the intermediate retinal plexus. Using in vitro and ex vivo Pdzrn3 loss-of-function and gain-of-function experiments, we demonstrate a key role of PDZRN3 in endothelial cell directional and coordinated extension. PDZRN3 ubiquitinates Dishevelled 3 (Dvl3), to promote endocytosis of the Frizzled/Dvl3 complex, for PCP signal transduction. These results highlight the role of PDZRN3 to direct Wnt PCP signalling, and broadly implicate this pathway in the planar orientation and highly branched organization of vascular plexuses.

  15. [Serine proteinases of lower vertebrates].

    PubMed

    Kolodzeĭskaia, M V

    1986-01-01

    Recent data on the effect of serine proteinases of lower vertebrates are generalized. Hydrolysis specificity and kinetics of different synthetic substrates, dependence of the activity of enzymes on pH, their irreversible inhibition by chloromethyl ketones of amino acids and peptides as well as high-molecular proteinase inhibitors are considered in detail. The data testify to the fact that chymotrypsins and trypsins of higher vertebrates and serine proteinases of lower vertebrates act as an acid-base catalysis. Enzymes in the pyloric cacca of fishes are in the state of proenzymes and are transformed into an active form with the aid of their own proteolytic factors. The esterase and proteolytic activity of fish proteinases is concentrated in the same active site and reaches the highest values at pH 7,8. New data are presented on particularities of the lower vertebrate proteinases, on the similarity and differences in their specificity. A distinct difference is shown in the nature of the binding site of the active centre in a number of serine proteinases of fishes as compared to chymotrypsin and trypsin of higher vertebrates.

  16. Ontogenetic cell death and phagocytosis in the visual system of vertebrates.

    PubMed

    Francisco-Morcillo, Javier; Bejarano-Escobar, Ruth; Rodríguez-León, Joaquín; Navascués, Julio; Martín-Partido, Gervasio

    2014-10-01

    Programmed cell death (PCD), together with cell proliferation, cell migration, and cell differentiation, is an essential process during development of the vertebrate nervous system. The visual system has been an excellent model on which to investigate the mechanisms involved in ontogenetic cell death. Several phases of PCD have been reported to occur during visual system ontogeny. During these phases, comparative analyses demonstrate that dying cells show similar but not identical spatiotemporally restricted patterns in different vertebrates. Additionally, the chronotopographical coincidence of PCD with the entry of specialized phagocytes in some regions of the developing vertebrate visual system suggests that factors released from degenerating cells are involved in the cell migration of macrophages and microglial cells. Contradicting this hypothesis however, in many cases the cell corpses generated during degeneration are rapidly phagocytosed by neighboring cells, such as neuroepithelial cells or Müller cells. In this review, we describe the occurrence and the sites of PCD during the morphogenesis and differentiation of the retina and optic pathways of different vertebrates, and discuss the possible relationship between PCD and phagocytes during ontogeny. Copyright © 2014 Wiley Periodicals, Inc.

  17. 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.

  18. Morphogenesis of the medaka cerebellum, with special reference to the mesencephalic sheet, a structure homologous to the rostrolateral part of mammalian anterior medullary velum.

    PubMed

    Ishikawa, Yuji; Yamamoto, Naoyuki; Yasuda, Takako; Yoshimoto, Masami; Ito, Hironobu

    2010-01-01

    We have examined cerebellar morphogenesis after neural tube stage in medaka (Oryzias latipes), a ray-finned fish, by conventional histology and immunohistochemistry using anti-proliferating cell nuclear antigen (PCNA) and anti-acetylated tubulin antibodies. Our results indicate that the medaka cerebellum is formed in 4 successive stages: (1) formation and enlargement of the cerebellar primordia; (2) rostral midline fusion of the left/right halves of the cerebellar primordia; (3) formation of the cerebellar matrix zones in the midline and caudalmost regions of the primitive cerebellum, and (4) growth and differentiation of the cerebellum. Our results also show that cerebellar morphogenesis is different from that in mammals in 3 important points: the developmental origins of the primordia, directions along which cerebellar fusion proceeds, and number, locations and duration of the cerebellar matrix zones. During the course of this study, an alar-derived membranous structure between the cerebellum and the midbrain in the adult medaka brain was identified as the structure homologous to the rostrolateral part of the mammalian anterior medullary velum. We have named this structure in the adult teleostean brains as the 'mesencephalic sheet'. The present study indicates that there exists both conserved and divergent patterns in cerebellar morphogenesis in vertebrates.

  19. Vestibular blueprint in early vertebrates

    PubMed Central

    Straka, Hans; Baker, Robert

    2013-01-01

    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. PMID:24312016

  20. Cuticle morphogenesis in crustacean embryonic and postembryonic stages.

    PubMed

    Mrak, Polona; Bogataj, Urban; Štrus, Jasna; Žnidaršič, Nada

    2017-01-01

    The crustacean cuticle is a chitin-based extracellular matrix, produced in general by epidermal cells and ectodermally derived epithelial cells of the digestive tract. Cuticle morphogenesis is an integrative part of embryonic and postembryonic development and it was studied in several groups of crustaceans, but mainly with a focus on one selected aspect of morphogenesis. Early studies were focused mainly on in vivo or histological observations of embryonic or larval molt cycles and more recently, some ultrastructural studies of the cuticle differentiation during development were performed. The aim of this paper is to review data on exoskeletal and gut cuticle formation during embryonic and postembryonic development in crustaceans, obtained in different developmental stages of different species and to bring together and discuss different aspects of cuticle morphogenesis, namely data on the morphology, ultrastructure, composition, connections to muscles and molt cycles in relation to cuticle differentiation. Based on the comparative evaluation of microscopic analyses of cuticle in crustacean embryonic and postembryonic stages, common principles of cuticle morphogenesis during development are discussed. Additional studies are suggested to further clarify this topic and to connect the new knowledge to related fields.

  1. Slit and Robo control cardiac cell polarity and morphogenesis.

    PubMed

    Qian, Li; Liu, Jiandong; Bodmer, Rolf

    2005-12-20

    Basic aspects of heart morphogenesis involving migration, cell polarization, tissue alignment, and lumen formation may be conserved between Drosophila and humans, but little is known about the mechanisms that orchestrate the assembly of the heart tube in either organism. The extracellular-matrix molecule Slit and its Robo-family receptors are conserved regulators of axonal guidance. Here, we report a novel role of the Drosophila slit, robo, and robo2 genes in heart morphogenesis. Slit and Robo proteins specifically accumulate at the dorsal midline between the bilateral myocardial progenitors forming a linear tube. Manipulation of Slit localization or its overexpression causes disruption in heart tube alignment and assembly, and slit-deficient hearts show disruptions in cell-polarity marker localization within the myocardium. Similar phenotypes are observed when Robo and Robo2 are manipulated. Rescue experiments suggest that Slit is secreted from the myocardial progenitors and that Robo and Robo2 act in myocardial and pericardial cells, respectively. Genetic interactions suggest a cardiac morphogenesis network involving Slit/Robo, cell-polarity proteins, and other membrane-associated proteins. We conclude that Slit and Robo proteins contribute significantly to Drosophila heart morphogenesis by guiding heart cell alignment and adhesion and/or by inhibiting cell mixing between the bilateral compartments of heart cell progenitors and ensuring proper polarity of the myocardial epithelium.

  2. Epithelial morphogenesis: the mouse eye as a model system.

    PubMed

    Chauhan, Bharesh; Plageman, Timothy; Lou, Ming; Lang, Richard

    2015-01-01

    Morphogenesis is the developmental process by which tissues and organs acquire the shape that is critical to their function. Here, we review recent advances in our understanding of the mechanisms that drive morphogenesis in the developing eye. These investigations have shown that regulation of the actin cytoskeleton is central to shaping the presumptive lens and retinal epithelia that are the major components of the eye. Regulation of the actin cytoskeleton is mediated by Rho family GTPases, by signaling pathways and indirectly, by transcription factors that govern the expression of critical genes. Changes in the actin cytoskeleton can shape cells through the generation of filopodia (that, in the eye, connect adjacent epithelia) or through apical constriction, a process that produces a wedge-shaped cell. We have also learned that one tissue can influence the shape of an adjacent one, probably by direct force transmission, in a process we term inductive morphogenesis. Though these mechanisms of morphogenesis have been identified using the eye as a model system, they are likely to apply broadly where epithelia influence the shape of organs during development. © 2015 Elsevier Inc. All rights reserved.

  3. Subtractive transcriptomics : establishing polarity drives human endothelial morphogenesis

    SciTech Connect

    Glesne, D. A.; Zhang, W.; Mandava, S.; Ursos, L.; Buell, M. E.; Makowski, L.; Rodi, D. J.; Biosciences Division

    2006-04-15

    Although investigations of mature normal and tumor-derived capillaries have resulted in characterization of these structures at the phenotypic level, less is known regarding the initial molecular cues for cellular assembly of endothelial cells into human capillaries. Here, we employ a novel combination of microenvironmental manipulation and microarray data filtration over narrowly delineated temporal data series to identify the morphogenesis component apart from the proliferation component, as pooled human microvascular-derived endothelial cells are induced to form capillary-like structures in vitro in a murine tumor-derived matrix. The 217 morphogenesis-specific genes identified using this subtractive transcriptomics approach are mostly independent of the angiogenic proteins currently used as therapeutic targets for aberrant angiogenesis. Quantitative real-time PCR was used to validate 20% of these transcripts. Immunofluorescent analysis of proliferating and tube-forming cells validates at the protein level the morphogenesis-specific expression pattern of 16 of the 217 gene products identified. The transcripts that are selectively up-regulated in tube-forming endothelial cells reveal a temporal expression pattern of genes primarily associated with intracellular trafficking, guided migration, cytoskeletal reorganization, cellular adhesion, and proliferation inhibition. These data show that a sequential upregulation of genes that establish and maintain polarity occurs during migration and morphogenesis of in vitro human endothelial cells undergoing tubulogenesis; some of which may well be effective as novel antiangiogenic drug targets.

  4. Serum factors involved in human microvascular endothelial cell morphogenesis.

    PubMed

    Harvey, Kevin; Siddiqui, Rafat A; Sliva, Daniel; Garcia, Joe G N; English, Denis

    2002-09-01

    Our previous studies have demonstrated that lipid and protein angiogenic factors operate in tandem to induce optimal angiogenic responses in vivo. This study was undertaken to clarify the nature of the substances in human serum that are responsible for its remarkable ability to promote capillary morphogenesis in vitro. The ability of dilute (2%) human serum to promote the morphogenic differentiation of human dermal microvascular endothelial cells on Matrigel supports was depleted by more than 50% by treatment of the serum with activated charcoal, a procedure that effectively removes biologically active lipid growth factors. The remainder of the activity within serum was lost on heating to 60 degrees C for 60 minutes, indicating the involvement of a protein in the response. The ability of charcoal-treated serum to promote capillary morphogenesis was completely restored by the addition of sphingosine 1-phosphate (SPP, 500 nmol/L), but other lipids thought to be released into serum during clotting were ineffective. In addition, basic fibroblast growth factor (bFGF) effectively restored the ability of heat-treated serum to promote endothelial cell morphogenesis, but other protein growth factors, including vascular endothelial growth factor and platelet-derived growth factor, were ineffective. Together, SPP and bFGF were as effective as whole serum in promoting capillary morphogenesis. Responses to purified SPP were entirely sensitive to the effects of preexposure of the cells to pertussis toxin, whereas responses to bFGF were entirely pertussis toxin-resistant. Consistent with our hypothesis that two distinct factors in serum play a role in promoting capillary morphogenesis, responses induced by serum were inhibited approximately 50% by preexposure of endothelial cells to pertussis toxin. We conclude that platelet-released SPP acts in conjunction with circulating bFGF to promote capillary formation by microvascular endothelial cells. Lipid and protein growth factors

  5. 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.

  6. Fibronectin Deposition Participates in Extracellular Matrix Assembly and Vascular Morphogenesis.

    PubMed

    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.

  7. Bmp inhibition is necessary for post-gastrulation patterning and morphogenesis of the zebrafish tailbud

    PubMed Central

    Row, Richard; Kimelman, David

    2009-01-01

    Summary Intricate interactions between the Wnt and Bmp signaling pathways pattern the gastrulating vertebrate embryo using a network of secreted protein ligands and inhibitors. While many of these proteins are expressed post-gastrula, their later roles have typically remained unclear, obscured by the effects of early perturbation. We find that Bmp signaling continues during somitogenesis in zebrafish embryos, with high activity in a small region of the mesodermal progenitor zone at the posterior end of the embryo. To test the hypothesis that Bmp inhibitors expressed just anterior to the tailbud are important to restrain Bmp signaling we produced a new zebrafish transgenic line, allowing temporal cell-autonomous activation of Bmp signaling and thereby bypassing the effects of the Bmp inhibitors. Ectopic activation of Bmp signaling during somitogenesis results in severe defects in the tailbud, including altered morphogenesis and gene expression. We show that these defects are due to non-autonomous effects on the tailbud, and present evidence that the tailbud defects are caused by alterations in Wnt signaling. We present a model in which the posteriorly expressed Bmp inhibitors function during somitogenesis to constrain Bmp signaling in the tailbud in order to allow normal expression of Wnt inhibitors in the presomitic mesoderm, which in turn constrain the levels of canonical and non-canonical Wnt signaling in the tailbud. PMID:19236859

  8. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking.

    PubMed

    Gault, William J; Olguin, Patricio; Weber, Ursula; Mlodzik, Marek

    2012-03-05

    Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes.

  9. Rap1 GTPase is required for mouse lens epithelial maintenance and morphogenesis.

    PubMed

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

    2015-10-01

    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.

  10. Connexin43 gap junction protein plays an essential role in morphogenesis of the embryonic chick face.

    PubMed

    McGonnell, I M; Green, C R; Tickle, C; Becker, D L

    2001-11-01

    Normal outgrowth and fusion of facial primordia during vertebrate development require interaction of diverse tissues and co-ordination of many different signalling pathways. Gap junction channels, made up of subunits consisting of connexin proteins, facilitate communication between cells and are implicated in embryonic development. Here we describe the distribution of connexin43 and connexin32 gap junction proteins in the developing chick face. To test the function of connexin43 protein, we applied antisense oligodeoxynucleotides that specifically reduced levels of connexin43 protein in cells of early chick facial primordia. This resulted in stunting of primordia outgrowth and led to facial defects. Furthermore, cell proliferation in regions of facial primordia that normally express high levels of connexin43 protein was reduced and this was associated with lower levels of Msx-1 expression. Facial defects arise when retinoic acid is applied to the face of chick embryos at later stages. This treatment also resulted in significant reduction in connexin43 protein, while connexin32 protein expression was unaffected. Taken together, these results indicate that connexin43 plays an essential role during early morphogenesis and subsequent outgrowth of the developing chick face.

  11. Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking

    PubMed Central

    Gault, William J.; Olguin, Patricio; Weber, Ursula

    2012-01-01

    Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes. PMID:22391037

  12. 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

  13. Grainy head and its target genes in epithelial morphogenesis and wound healing.

    PubMed

    Wang, Shenqiu; Samakovlis, Christos

    2012-01-01

    The Grainy head (Grh) family of transcription factors is characterized by a unique DNA-binding domain that binds to a conserved consensus sequence. Nematodes and flies have a single grh gene, whereas mice and humans have evolved three genes encoding Grainy head-like (Grhl) factors. We review the biological function of Grh in different animals and the mechanisms modulating its activity. grh and grhl genes play a remarkably conserved role in epithelial organ development and extracellular barrier repair after tissue damage. Recent studies in flies and vertebrates suggest that Grh factors may be primary determinants of cell adhesion and epithelial tissue formation. Grh proteins can dimerize and act as activators or repressors in different developmental contexts. In flies, tissue-specific, alternative splicing generates different Grh isoforms with different DNA-binding specificities and functions. Grh activity is also modulated by receptor tyrosine kinases: it is phosphorylated by extracellular signal regulated kinase, and this phosphorylation is selectively required for epidermal barrier repair. Two mechanisms have been proposed to explain the repressive function of Grh on target gene transcription. First, Grh can target the Polycomb silencing complex to specific response elements. Second, it can directly compete for DNA binding with transcriptional activators. Understanding the molecular mechanisms of gene regulation by Grh factors is likely to elucidate phylogenetically conserved mechanisms of epithelial cell morphogenesis and regeneration upon tissue damage.

  14. Learning about Vertebrate Limb Development

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  15. Learning about Vertebrate Limb Development

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  16. Vertebrate Embryonic Cleavage Pattern Determination.

    PubMed

    Hasley, Andrew; Chavez, Shawn; Danilchik, Michael; Wühr, Martin; Pelegri, Francisco

    2017-01-01

    The pattern of the earliest cell divisions in a vertebrate embryo lays the groundwork for later developmental events such as gastrulation, organogenesis, and overall body plan establishment. Understanding these early cleavage patterns and the mechanisms that create them is thus crucial for the study of vertebrate development. This chapter describes the early cleavage stages for species representing ray-finned fish, amphibians, birds, reptiles, mammals, and proto-vertebrate ascidians and summarizes current understanding of the mechanisms that govern these patterns. The nearly universal influence of cell shape on orientation and positioning of spindles and cleavage furrows and the mechanisms that mediate this influence are discussed. We discuss in particular models of aster and spindle centering and orientation in large embryonic blastomeres that rely on asymmetric internal pulling forces generated by the cleavage furrow for the previous cell cycle. Also explored are mechanisms that integrate cell division given the limited supply of cellular building blocks in the egg and several-fold changes of cell size during early development, as well as cytoskeletal specializations specific to early blastomeres including processes leading to blastomere cohesion. Finally, we discuss evolutionary conclusions beginning to emerge from the contemporary analysis of the phylogenetic distributions of cleavage patterns. In sum, this chapter seeks to summarize our current understanding of vertebrate early embryonic cleavage patterns and their control and evolution.

  17. The ISCD and Vertebral Fractures.

    PubMed

    Vokes, Tamara; Lentle, Brian

    2016-01-01

    Some 30 years ago the diagnosis of osteoporosis relied primarily on the measurement of bone mineral density by DXA. More recently, however, it was recognized that vertebral fractures are an important predictor of future fractures and that they reflect some aspect of bone fragility not captured by BMD measurement. In response to that, DXA manufacturers developed VFA, spine imaging on the densitometer, which allowed integration of BMD with information on vertebral fractures obtained at the same visit. ISCD has been instrumental in several aspects of VFA use such as developing and teaching courses for VFA or more broadly, for recognition of vertebral fractures; in developing guidelines for performance, interpretation and reporting of the VFA; and in advocating for reimbursement for VFA tests performed in the clinical practice. ISCD is poised to continue as a leader in vertebral fracture recognition and application of VFA to clinical practice and research. Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  18. The Morphogenesis of Cranial Sutures in Zebrafish

    PubMed Central

    Topczewska, Jolanta M.; Shoela, Ramy A.; Tomaszewski, Joanna P.; Mirmira, Rupa B.; Gosain, Arun K.

    2016-01-01

    Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone. Parietal and frontal bones are formed by intramembranous ossification within a layer of mesenchyme positioned between the dermal mesenchyme and meninges surrounding the brain. The supraoccipital bone has an endochondral origin. Cranial bones are separated by connective tissue with a distinctive architecture of osteogenic cells and collagen fibrils. Here we show RNA in situ hybridization for col1a1a, col2a1a, col10a1, bglap/osteocalcin, fgfr1a, fgfr1b, fgfr2, fgfr3, foxq1, twist2, twist3, runx2a, runx2b, sp7/osterix, and spp1/ osteopontin, indicating that the expression of genes involved in suture development in mammals is preserved in zebrafish. We also present methods for examining the cranium and its sutures, which permit the study of the mechanisms involved in suture patency as well as their pathological obliteration. The model we develop has implications for the study of human disorders, including craniosynostosis, which affects 1 in 2,500 live births. PMID:27829009

  19. Detangling the evolutionary developmental integration of dentate jaws: evidence that a p63 gene network regulates odontogenesis exclusive of mandible morphogenesis.

    PubMed

    Raj, Muhammad T; Boughner, Julia C

    2016-12-01

    Vertebrate jaws and dentitions fit and function together, yet the genetic processes that coordinate cranial and dental morphogenesis and evolution remain poorly understood. Teeth but not jaws fail to form in the edentate p63(-/-) mouse mutant, which we used here to identify genes important to odontogenesis, but not jaw morphogenesis, and that may allow dentitions to change during development and evolution without necessarily affecting the jaw skeleton. With the working hypothesis that tooth and jaw development are autonomously controlled by discreet gene regulatory networks, using gene expression microarray assays validated by quantitative reverse-transcription PCR we contrasted expression in mandibular prominences at embryonic days (E) 10-13 of mice with normal lower jaw development but either normal (p63(+/-) , p63(+/+) ) or arrested (p63(-/-) ) tooth development. The p63(-/-) mice showed significantly different expression (fold change ≥2, ≤-2; P ≤ 0.05) of several genes. Some of these are known to help regulate odontogenesis (e.g., p63, Osr2, Cldn3/4) and/or to be targets of p63 (e.g., Jag1/2, Fgfr2); other genes have no previously reported roles in odontogenesis or the p63 pathway (e.g., Fermt1, Cbln1, Pltp, Krt8). As expected, from E10 to E13, few genes known to regulate mandible morphogenesis differed in expression between mouse strains. This study newly links several genes to odontogenesis and/or to the p63 signaling network. We propose that these genes act in a novel odontogenic network that is exclusive of lower jaw morphogenesis, and posit that this network evolved in oral, not pharyngeal, teeth. © 2016 Wiley Periodicals, Inc.

  20. Symptomatic vertebral hemangiomas during pregnancy.

    PubMed

    Moles, Alexis; Hamel, Olivier; Perret, Christophe; Bord, Eric; Robert, Roger; Buffenoir, Kevin

    2014-05-01

    Symptomatic vertebral hemangiomas during pregnancy are rare, as only 27 cases have been reported in the literature since 1948. However, symptomatic vertebral hemangiomas can be responsible for spinal cord compression, in which case they constitute a medical emergency, which raises management difficulties in the context of pregnancy. Pregnancy is a known factor responsible for deterioration of these vascular tumors. In this paper, the authors report 2 clinical cases of symptomatic vertebral hemangiomas during pregnancy, including 1 case of spontaneous fracture that has never been previously reported in the literature. The authors then present a brief review of the literature to discuss emergency management of this condition. The first case was a 28-year-old woman at 35 weeks of gestation, who presented with paraparesis. Spinal cord MRI demonstrated a vertebral hemangioma invading the body and posterior arch of T-3 with posterior epidural extension. Laminectomy and vertebroplasty were performed after cesarean section, allowing neurological recovery. The second case involved a 35-year-old woman who presented with spontaneous fracture of T-7 at 36 weeks of gestation, revealing a vertebral hemangioma with no neurological deficit, but it was responsible for pain and local instability. Treatment consisted of postpartum posterior interbody fusion. With a clinical and radiological follow-up of 2 years, no complications and no modification of the hemangiomas were observed. A review of the literature reveals discordant management of these rare cases, which is why the treatment course must be decided by a multidisciplinary team as a function of fetal gestational age and maternal neurological features.

  1. Early development of the vertebral column.

    PubMed

    Scaal, Martin

    2016-01-01

    The segmental organization of the vertebrate body is most obviously visible in the vertebral column, which consists of a series of vertebral bones and interconnecting joints and ligaments. During embryogenesis, the vertebral column derives from the somites, which are the primary segments of the embryonic paraxial mesoderm. Anatomical, cellular and molecular aspects of vertebral column development have been of interest to developmental biologists for more than 150 years. This review briefly summarizes the present knowledge on early steps of vertebral column development in amniotes, starting from sclerotome formation and leading to the establishment of the anatomical bauplan of the spine composed of vertebral bodies, vertebral arches, intervertebral discs and ribs, and their specific axial identities along the body axis.

  2. 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

  3. Vertebral Augmentation for Osteoporotic Compression Fractures.

    PubMed

    Richmond, Bradford J

    2016-01-01

    Vertebral augmentation procedures such as vertebroplasty and kyphoplasty were developed to reduce pain and improve quality of life for patients with osteoporotic vertebral compression fractures. However, the use of vertebral augmentation has been debated and questioned since its inception. This article addresses some of these issues.

  4. Cervical vertebral bone age in girls.

    PubMed

    Mito, Toshinori; Sato, Koshi; Mitani, Hideo

    2002-10-01

    The purpose of this study was to establish cervical vertebral bone age as a new index for objectively evaluating skeletal maturation on cephalometric radiographs. Using cephalometric radiographs of 176 girls (ages 7.0-14.9 years), we measured cervical vertebral bodies and determined a regression formula to obtain cervical vertebral bone age. Next, using cephalometric and hand-wrist radiographs of another 66 girls (ages 8.0-13.9 years), we determined the correlation between cervical vertebral bone age and bone age using the Tanner-Whitehouse 2 method. The following results were obtained: (1) a regression formula was determined to obtain cervical vertebral bone age based on ratios of measurements in the third and fourth cervical vertebral bodies; (2) the correlation coefficient for the relationship between cervical vertebral bone age and bone age (0.869) was significantly (P <.05) higher than that for the relationship between cervical vertebral bone age and chronological age (0.705); and (3) the difference (absolute value) between the cervical vertebral bone age and bone age (0.75 years) was significantly (P <.001) smaller than that between cervical vertebral bone age and chronological age (1.17 years). These results suggest that cervical vertebral bone age reflects skeletal maturity because it approximates bone age, which is considered to be the most reliable method for evaluating skeletal maturation. Using cervical vertebral bone age, it might be possible to evaluate maturity in a detailed and objective manner on cephalometric radiographs.

  5. GLUT10 is required for the development of the cardiovascular system and the notochord and connects mitochondrial function to TGFβ signaling.

    PubMed

    Willaert, Andy; Khatri, Sandeep; Callewaert, Bert L; Coucke, Paul J; Crosby, Seth D; Lee, Joseph G H; Davis, Elaine C; Shiva, Sruti; Tsang, Michael; De Paepe, Anne; Urban, Zsolt

    2012-03-15

    Growth factor signaling results in dramatic phenotypic changes in cells, which require commensurate alterations in cellular metabolism. Mutations in SLC2A10/GLUT10, a member of the facilitative glucose transporter family, are associated with altered transforming growth factor-β (TGFβ) signaling in patients with arterial tortuosity syndrome (ATS). The objective of this work was to test whether SLC2A10/GLUT10 can serve as a link between TGFβ-related transcriptional regulation and metabolism during development. In zebrafish embryos, knockdown of slc2a10 using antisense morpholino oligonucleotide injection caused a wavy notochord and cardiovascular abnormalities with a reduced heart rate and blood flow, which was coupled with an incomplete and irregular vascular patterning. This was phenocopied by treatment with a small-molecule inhibitor of TGFβ receptor (tgfbr1/alk5). Array hybridization showed that the changes at the transcriptome level caused by the two treatments were highly correlated, revealing that a reduced tgfbr1 signaling is a key feature of ATS in early zebrafish development. Interestingly, a large proportion of the genes, which were specifically dysregulated after glut10 depletion gene and not by tgfbr1 inhibition, play a major role in mitochondrial function. Consistent with these results, slc2a10 morphants showed decreased respiration and reduced TGFβ reporter gene activity. Finally, co-injection of antisense morpholinos targeting slc2a10 and smad7 (a TGFβ inhibitor) resulted in a partial rescue of smad7 morphant phenotypes, suggesting scl2a10/glut10 functions downstream of smads. Taken together, glut10 is essential for cardiovascular development by facilitating both mitochondrial respiration and TGFβ signaling.

  6. The temporal dynamics of vertebrate limb development, teratogenesis and evolution.

    PubMed

    Zeller, Rolf

    2010-08-01

    Recent genetic and functional analysis of vertebrate limb development begins to reveal how the functions of particular genes and regulatory hierarchies can drastically change over time. The temporal and spatial interplay of the two instructive signalling centres are part of a larger signalling system that orchestrates limb bud morphogenesis in a rather self-regulatory manner. It appears that mesenchymal cells are specified early and subsequently, the progenitors for the different skeletal elements are expanded and determined progressively during outgrowth. Mutations and teratogens that disrupt distal progression of limb development most often cause death of the early-specified progenitors rather than altering their fates. The proliferative expansion and distal progression of paired appendage development was one of the main driving forces behind the transition from fin to limb buds during paired appendage evolution. Finally, the adaptive diversification or loss of modern tetrapod limbs in particular phyla or species appear to be a consequence of evolutionary tampering with the regulatory systems that control distal progression of limb development.

  7. The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling

    PubMed Central

    2013-01-01

    Background The pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke’s pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke’s pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance. Results We show that Rathke’s pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polarisfl/fl; Wnt1-Cre, Ofd1-/- and Kif3a-/- primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1-/- mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling. Conclusion These results provide insight into a poorly

  8. Morphological castes in a vertebrate

    PubMed Central

    O'Riain, M. J.; Jarvis, J. U. M.; Alexander, R.; Buffenstein, R.; Peeters, C.

    2000-01-01

    Morphological specialization for a specific role has, until now, been assumed to be restricted to social invertebrates. Herein we show that complete physical dimorphism has evolved between reproductives and helpers in the eusocial naked mole-rat. Dimorphism is a consequence of the lumbar vertebrae lengthening after the onset of reproduction in females. This is the only known example of morphological castes in a vertebrate and is distinct from continuous size variation between breeders and helpers in other species of cooperatively breeding vertebrates. The evolution of castes in a mammal and insects represents a striking example of convergent evolution for enhanced fecundity in societies characterized by high reproductive skew. Similarities in the selective environment between naked mole-rats and eusocial insect species highlight the selective conditions under which queen/worker castes are predicted to evolve in animal societies. PMID:11087866

  9. Climate change and marine vertebrates.

    PubMed

    Sydeman, William J; Poloczanska, Elvira; Reed, Thomas E; Thompson, Sarah Ann

    2015-11-13

    Climate change impacts on vertebrates have consequences for marine ecosystem structures and services. We review marine fish, mammal, turtle, and seabird responses to climate change and discuss their potential for adaptation. Direct and indirect responses are demonstrated from every ocean. Because of variation in research foci, observed responses differ among taxonomic groups (redistributions for fish, phenology for seabirds). Mechanisms of change are (i) direct physiological responses and (ii) climate-mediated predator-prey interactions. Regional-scale variation in climate-demographic functions makes range-wide population dynamics challenging to predict. The nexus of metabolism relative to ecosystem productivity and food webs appears key to predicting future effects on marine vertebrates. Integration of climate, oceanographic, ecosystem, and population models that incorporate evolutionary processes is needed to prioritize the climate-related conservation needs for these species. Copyright © 2015, American Association for the Advancement of Science.

  10. [Morphogenesis and the fine structure of Stibiobacter senarmontii].

    PubMed

    Pivovarova, T A; Lialikova, N N

    1980-01-01

    The morphogenesis and fine structure of Stibiobacter senarmontii were studied during its cultivation in the autotrophic conditions of growth in a mineral medium as well as in a medium containing yeast extract. The morphology of the organism was shown to be variable. A young culture was represented mainly by rods with three flagella. Coccoid, club-shaped and branching forms were observed during aging of the culture. The cells multiplied by irregular division and by breaking along the partition of the parent cell. The latter process yielded cell aggregates looking like rings and hieroglyphs. Electronograms revealed a complex membrane apparatus, polyribosomes, large electron-transparent inclusions, and unknown electron-dense inclusions in the nuclear zone. The cell wall looked on cross-sections as a three-layer structure. The assignment of St. senarmontii to Gram-positive bacteria is discussed. The morphogenesis of this organism suggests that it is related to the coryneform group of bacteria.

  11. The evolution of fungal morphogenesis, a personal account.

    PubMed

    Bartnicki-Garcia, Salomon

    2016-01-01

    This article describes the evolution of the field of fungal morphogenesis, its beginning at the end of the 19th century and its exponential growth during the second half of the 20th century, continuing until the present day. The main theme correlates biological progress with the advent of new technologies. Accordingly the article describes the discovery of apical growth, the fibrillar nature of the fungal wall, the chemistry of the cell wall, the search for biochemical pathways in morphogenesis, the discovery of the Spitzenkörper, the apical gradient of wall synthesis, key highlights in ultrastructural research, the development of mathematical models particularly the vesicle supply center (VSC) model, the revolution brought about by molecular biology and unique discoveries such as the hydrophobins and γ-tubulin and some the latest triumphs of the marriage between molecular genetics and confocal microscopy. Credit is given to the investigators responsible for all the advances.

  12. The unfolded protein response is required for dendrite morphogenesis.

    PubMed

    Wei, Xing; Howell, Audrey S; Dong, Xintong; Taylor, Caitlin A; Cooper, Roshni C; Zhang, Jianqi; Zou, Wei; Sherwood, David R; Shen, Kang

    2015-06-08

    Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homolog of mammalian BiP/grp78). Surprisingly, a single transmembrane leucine-rich repeat protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors.

  13. MicroRNAs regulate brain morphogenesis in zebrafish.

    PubMed

    Giraldez, Antonio J; Cinalli, Ryan M; Glasner, Margaret E; Enright, Anton J; Thomson, J Michael; Baskerville, Scott; Hammond, Scott M; Bartel, David P; Schier, Alexander F

    2005-05-06

    MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally. To block all miRNA formation in zebrafish, we generated maternal-zygotic dicer (MZdicer) mutants that disrupt the Dicer ribonuclease III and double-stranded RNA-binding domains. Mutant embryos do not process precursor miRNAs into mature miRNAs, but injection of preprocessed miRNAs restores gene silencing, indicating that the disrupted domains are dispensable for later steps in silencing. MZdicer mutants undergo axis formation and differentiate multiple cell types but display abnormal morphogenesis during gastrulation, brain formation, somitogenesis, and heart development. Injection of miR-430 miRNAs rescues the brain defects in MZdicer mutants, revealing essential roles for miRNAs during morphogenesis.

  14. 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

  15. Fungal quorum sensing molecules: Role in fungal morphogenesis and pathogenicity.

    PubMed

    Wongsuk, Thanwa; Pumeesat, Potjaman; Luplertlop, Natthanej

    2016-05-01

    When microorganisms live together in high numbers, they need to communicate with each other. To achieve cell-cell communication, microorganisms secrete molecules called quorum-sensing molecules (QSMs) that control their biological activities and behaviors. Fungi secrete QSMs such as farnesol, tyrosol, phenylethanol, and tryptophol. The role of QSMs in fungi has been widely studied in both yeasts and filamentous fungi, for example in Candida albicans, C. dubliniensis, Aspergillus niger, A. nidulans, and Fusarium graminearum. QSMs impact fungal morphogenesis (yeast-to-hypha formation) and also play a role in the germination of macroconidia. QSMs cause fungal cells to initiate programmed cell death, or apoptosis, and play a role in fungal pathogenicity. Several types of QSMs are produced during stages of biofilm development to control cell population or morphology in biofilm communities. This review article emphasizes the role of fungal QSMs, especially in fungal morphogenesis, biofilm formation, and pathogenicity. Information about QSMs may lead to improved measures for controlling fungal infection.

  16. 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.

  17. Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis

    PubMed Central

    Swinehart, Ilea T.; Badylak, Stephen F.

    2016-01-01

    During normal morphogenesis the extracellular matrix (ECM) influences cell motility, proliferation, apoptosis, and differentiation. Tissue engineers have attempted to harness the cell signaling potential of ECM to promote the functional reconstruction, if not regeneration, of injured or missing adult tissues that otherwise heal by the formation of scar tissue. ECM bioscaffolds, derived from decellularized tissues, have been used to promote the formation of site appropriate, functional tissues in many clinical applications including skeletal muscle, fibrocartilage, lower urinary tract, and esophageal reconstruction, among others. These scaffolds function by the release or exposure of growth factors and cryptic peptides, modulation of the immune response, and recruitment of progenitor cells. Herein, we describe this process of ECM induced constructive remodeling and examine similarities to normal tissue morphogenesis. PMID:26699796

  18. Polarized Protein Transport and Lumen Formation During Epithelial Tissue Morphogenesis

    PubMed Central

    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. PMID:26359775

  19. Three-dimensional vertex model for simulating multicellular morphogenesis

    PubMed Central

    Okuda, Satoru; Inoue, Yasuhiro; Adachi, Taiji

    2015-01-01

    During morphogenesis, various cellular activities are spatiotemporally coordinated on the protein regulatory background to construct the complicated, three-dimensional (3D) structures of organs. Computational simulations using 3D vertex models have been the focus of efforts to approach the mechanisms underlying 3D multicellular constructions, such as dynamics of the 3D monolayer or multilayer cell sheet like epithelia as well as the 3D compacted cell aggregate, including dynamic changes in layer structures. 3D vertex models enable the quantitative simulation of multicellular morphogenesis on the basis of single-cell mechanics, with complete control of various cellular activities such as cell contraction, growth, rearrangement, division, and death. This review describes the general use of the 3D vertex model, along with its applications to several simplified problems of developmental phenomena. PMID:27493850

  20. Oscarella lobularis (Homoscleromorpha, Porifera) Regeneration: Epithelial Morphogenesis and Metaplasia

    PubMed Central

    Ereskovsky, Alexander V.; Borisenko, Ilya E.; Lapébie, Pascal; Gazave, Eve; Tokina, Daria B.; Borchiellini, Carole

    2015-01-01

    Sponges are known to possess remarkable reconstitutive and regenerative abilities ranging from common wounding or body part regeneration to more impressive re-building of a functional body from dissociated cells. Among the four sponge classes, Homoscleromorpha is notably the only sponge group to possess morphologically distinct basement membrane and specialized cell-junctions, and is therefore considered to possess true epithelia. The consequence of this peculiar organization is the predominance of epithelial morphogenesis during ontogenesis of these sponges. In this work we reveal the underlying cellular mechanisms used during morphogenesis accompanying ectosome regeneration in the homoscleromorph sponge model: Oscarella lobularis. We identified three main sources of novel exopinacoderm during the processes of its regeneration and the restoration of functional peripheral parts of the aquiferous system in O. lobularis: (1) intact exopinacoderm surrounding the wound surface, (2) the endopinacoderm from peripheral exhalant and inhalant canals, and (3) the intact choanoderm found on the wound surface. The basic morphogenetic processes during regeneration are the spreading and fusion of epithelial sheets that merge into one continuous epithelium. Transdifferentiation of choanocytes into exopinacocytes is also present. Epithelial-mesenchymal transition is absent during regeneration. Moreover, we cannot reveal any other morphologically distinct pluripotent cells. In Oscarella, neither blastema formation nor local dedifferentiation and proliferation have been detected, which is probably due to the high morphogenetic plasticity of the tissue. Regeneration in O. lobularis goes through cell transdifferentiation and through the processes, when lost body parts are replaced by the remodeling of the remaining tissue. Morphogenesis during ectosome regeneration in O. lobularis is correlated with its true epithelial organization. Knowledge of the morphological basis of

  1. Oscarella lobularis (Homoscleromorpha, Porifera) Regeneration: Epithelial Morphogenesis and Metaplasia.

    PubMed

    Ereskovsky, Alexander V; Borisenko, Ilya E; Lapébie, Pascal; Gazave, Eve; Tokina, Daria B; Borchiellini, Carole

    2015-01-01

    Sponges are known to possess remarkable reconstitutive and regenerative abilities ranging from common wounding or body part regeneration to more impressive re-building of a functional body from dissociated cells. Among the four sponge classes, Homoscleromorpha is notably the only sponge group to possess morphologically distinct basement membrane and specialized cell-junctions, and is therefore considered to possess true epithelia. The consequence of this peculiar organization is the predominance of epithelial morphogenesis during ontogenesis of these sponges. In this work we reveal the underlying cellular mechanisms used during morphogenesis accompanying ectosome regeneration in the homoscleromorph sponge model: Oscarella lobularis. We identified three main sources of novel exopinacoderm during the processes of its regeneration and the restoration of functional peripheral parts of the aquiferous system in O. lobularis: (1) intact exopinacoderm surrounding the wound surface, (2) the endopinacoderm from peripheral exhalant and inhalant canals, and (3) the intact choanoderm found on the wound surface. The basic morphogenetic processes during regeneration are the spreading and fusion of epithelial sheets that merge into one continuous epithelium. Transdifferentiation of choanocytes into exopinacocytes is also present. Epithelial-mesenchymal transition is absent during regeneration. Moreover, we cannot reveal any other morphologically distinct pluripotent cells. In Oscarella, neither blastema formation nor local dedifferentiation and proliferation have been detected, which is probably due to the high morphogenetic plasticity of the tissue. Regeneration in O. lobularis goes through cell transdifferentiation and through the processes, when lost body parts are replaced by the remodeling of the remaining tissue. Morphogenesis during ectosome regeneration in O. lobularis is correlated with its true epithelial organization. Knowledge of the morphological basis of

  2. Formation of the digestive system in zebrafish. I. Liver morphogenesis.

    PubMed

    Field, Holly A; Ober, Elke A; Roeser, Tobias; Stainier, Didier Y R

    2003-01-15

    Despite the essential functions of the digestive system, much remains to be learned about the cellular and molecular mechanisms responsible for digestive organ morphogenesis and patterning. We introduce a novel zebrafish transgenic line, the gutGFP line, that expresses GFP throughout the digestive system, and use this tool to analyze the development of the liver. Our studies reveal two phases of liver morphogenesis: budding and growth. The budding period, which can be further subdivided into three stages, starts when hepatocytes first aggregate, shortly after 24 h postfertilization (hpf), and ends with the formation of a hepatic duct at 50 hpf. The growth phase immediately follows and is responsible for a dramatic alteration of liver size and shape. We also analyze gene expression in the developing liver and find a correlation between the expression of certain transcription factor genes and the morphologically defined stages of liver budding. To further expand our understanding of budding morphogenesis, we use loss-of-function analyses to investigate factors potentially involved in this process. It had been reported that no tail mutant embryos appear to lack a liver primordium, as assessed by gata6 expression. However, analysis of gutGFP embryos lacking Ntl show that the liver is in fact present. We also find that, in these embryos, the direction of liver budding does not correlate with the direction of intestinal looping, indicating that the left/right behavior of these tissues can be uncoupled. In addition, we use the cloche mutation to analyze the role of endothelial cells in liver morphogenesis, and find that in zebrafish, unlike what has been reported in mouse, endothelial cells do not appear to be necessary for the budding of this organ.

  3. 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.

  4. Septin Function in Candida albicans MorphogenesisD⃞

    PubMed Central

    Warenda, Amy J.; Konopka, James B.

    2002-01-01

    The septin proteins function in the formation of septa, mating projections, and spores in Saccharomyces cerevisiae, as well as in cell division and other processes in animal cells. Candida albicans septins were examined in this study for their roles in morphogenesis of this multimorphic, opportunistically pathogenic fungus, which can range from round budding yeast to elongated hyphae. C. albicans green fluorescent protein labeled septin proteins localized to a tight ring at the bud and pseudohyphae necks and as a more diffuse array in emerging germ tubes of hyphae. Deletion analysis demonstrated that the C. albicans homologs of the S. cerevisiae CDC3 and CDC12 septins are essential for viability. In contrast, the C. albicans cdc10Δ and cdc11Δ mutants were viable but displayed conditional defects in cytokinesis, localization of cell wall chitin, and bud morphology. The mutant phenotypes were not identical, however, indicating that these septins carry out distinct functions. The viable septin mutants could be stimulated to undergo hyphal morphogenesis but formed hyphae with abnormal curvature, and they differed from wild type in the selection of sites for subsequent rounds of hyphal formation. The cdc11Δ mutants were also defective for invasive growth when embedded in agar. These results further extend the known roles of the septins by demonstrating that they are essential for the proper morphogenesis of C. albicans during both budding and filamentous growth. PMID:12181342

  5. Morphogenesis, Dictyostelium, and the search for shared developmental processes.

    PubMed

    Sunderland, Mary Evelyn

    2011-12-01

    In the 1930s John Tyler Bonner began studying the slime mold, Dictyostelium discoideum, as a way to investigate how organisms develop. With a life cycle that includes periods of unicellularity and multicellularity, Dictyostelium raises questions fundamental to development and evolution. In Morphogenesis: An Essay on Development (1952), Bonner built on his work with Dictyostelium to inform developmental theory and practice. By exploring how Bonner's early work with Dictyostelium motivated his synthetic approach in Morphogenesis, this paper presents an example of how those who studied development sought ways to gain traction in the rapidly changing life sciences. While a biochemical viewpoint of development became dominant, morphogenesis provided a way to reintroduce and emphasize biological organization at the organismal level. Bonner's early work offers a window to mid-twentieth century studies of development, an understudied area in the history of science, and shows that it was a time when growing experimental evidence enabled new ways of thinking about the relationship between ontogeny and evolution, and more broadly, about how the parts of nature might fit together.

  6. Testing Turing's Theory of Morphogenesis in Chemical Cells

    NASA Astrophysics Data System (ADS)

    Tompkins, Nathan; Li, Ning; Girabawe, Camille; Heymann, Michael; Ermentrout, G. Bard; Epstein, Irving; Fraden, Seth

    2015-03-01

    Alan Turing's 1952 paper ``The Chemical Basis of Morphogenesis'' described how reaction-diffusion dynamics could create six spatiotemporal patterns including a stationary pattern that could lead to physical morphogenesis (which now bears his name). This stationary ``Turing pattern'' has been observed in continuous media of various chemical systems but never in diffusively coupled discrete reactors as Turing theorized. We have created a system of microfluidically produced chemical compartments containing the Belousov-Zhabotinsky reaction that are designed to fulfill the assumptions of Turing's theoretical system. This system demonstrates all six spatiotemporal patterns that Turing predicted. In particular, we observe the stationary case that bears Turing's name where the cells create a pattern of oxidized and reduced states. As Turing predicted, this chemical heterogeneity gives rise to physical heterogeneity by driving an osmotic flow, swelling the reduced cells and shrinking the oxidized cells. In addition to the six patterns and physical morphogenesis predicted by Turing we observe a seventh pattern of mixed stationary/oscillatory states that is not predicted by Turing. This seventh pattern requires modifying Turing's theory to include slight heterogeneity to match experiments.

  7. Comparative analysis of neural crest cell death, migration, and function during vertebrate embryogenesis.

    PubMed

    Kulesa, Paul; Ellies, Debra L; Trainor, Paul A

    2004-01-01

    Cranial neural crest cells are a multipotent, migratory population that generates most of the cartilage, bone, connective tissue and peripheral nervous system in the vertebrate head. Proper neural crest cell patterning is essential for normal craniofacial morphogenesis and is highly conserved among vertebrates. Neural crest cell patterning is intimately connected to the early segmentation of the neural tube, such that neural crest cells migrate in discrete segregated streams. Recent advances in live embryo imaging have begun to reveal the complex behaviour of neural crest cells which involve intricate cell-cell and cell-environment interactions. Despite the overall similarity in neural crest cell migration between distinct vertebrates species there are important mechanistic differences. Apoptosis for example, is important for neural crest cell patterning in chick embryos but not in mouse, frog or fish embryos. In this paper we highlight the potential evolutionary significance of such interspecies differences in jaw development and evolution. Developmental Dynamics 229:14-29, 2004. Copyright 2003 Wiley-Liss, Inc.

  8. Morphogenesis-independent regulation of actin transcript levels in the pathogenic yeast Candida albicans.

    PubMed

    Delbrück, S; Ernst, J F

    1993-11-01

    The transcript level of the Candida albicans ACT1 gene (encoding actin) is strongly regulated during induction of hyphal morphogenesis. ACT1 mRNA declines rapidly during starvation pretreatment and quickly recovers in media inducing morphogenesis. The C. albicans URA3 and LEU2 mRNAs, as well as an ACT1 promoter/LAC4 fusion, are regulated similarly. The regulation of ACT1/LAC4 and unaltered mRNA stabilities suggest transcriptional regulation during morphogenesis. However, by individually testing morphogenesis induction parameters, it is shown that starvation and growth phase, but not hyphal formation, are responsible for ACT1 transcript regulation; this conclusion is confirmed by analyses of morphological mutants and by inhibition of hyphal development. Thus, the specific morphogenesis-induction conditions, but not morphogenesis per se, affect transcript levels in C. albicans.

  9. An emerging role for prdm family genes in dorsoventral patterning of the vertebrate nervous system.

    PubMed

    Zannino, Denise A; Sagerström, Charles G

    2015-10-24

    The embryonic vertebrate neural tube is divided along its dorsoventral (DV) axis into eleven molecularly discrete progenitor domains. Each of these domains gives rise to distinct neuronal cell types; the ventral-most six domains contribute to motor circuits, while the five dorsal domains contribute to sensory circuits. Following the initial neurogenesis step, these domains also generate glial cell types-either astrocytes or oligodendrocytes. This DV pattern is initiated by two morphogens-Sonic Hedgehog released from notochord and floor plate and Bone Morphogenetic Protein produced in the roof plate-that act in concentration gradients to induce expression of genes along the DV axis. Subsequently, these DV-restricted genes cooperate to define progenitor domains and to control neuronal cell fate specification and differentiation in each domain. Many genes involved in this process have been identified, but significant gaps remain in our understanding of the underlying genetic program. Here we review recent work identifying members of the Prdm gene family as novel regulators of DV patterning in the neural tube. Many Prdm proteins regulate transcription by controlling histone modifications (either via intrinsic histone methyltransferase activity, or by recruiting histone modifying enzymes). Prdm genes are expressed in spatially restricted domains along the DV axis of the neural tube and play important roles in the specification of progenitor domains, as well as in the subsequent differentiation of motor neurons and various types of interneurons. Strikingly, Prdm proteins appear to function by binding to, and modulating the activity of, other transcription factors (particularly bHLH proteins). The identity of key transcription factors in DV patterning of the neural tube has been elucidated previously (e.g. the nkx, bHLH and pax families), but it now appears that an additional family is also required and that it acts in a potentially novel manner.

  10. 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 many

  11. Fission yeast leucine-rich repeat protein Lrp1 is essential for cell morphogenesis as a component of the morphogenesis Orb6 network (MOR).

    PubMed

    Kume, Kazunori; Kubota, Shunsuke; Koyano, Takayuki; Kanai, Muneyoshi; Mizunuma, Masaki; Toda, Takashi; Hirata, Dai

    2013-01-01

    In eukaryotes, cell morphogenesis is regulated coordinately with the cell cycle. In fission yeast, the morphogenesis network MOR (morphogenesis Orb6 network) consists of 5 conserved proteins, Pmo25, Nak1, Mor2, Orb6, and Mob2, and is essential for cell polarity control and cell separation following cytokinesis. Here we show that the conserved leucine-rich repeat protein Lrp1 is required for cell morphogenesis as a newly recognized component of MOR. Lrp1 has 4 leucine-rich repeats in its N-terminus and is a homolog of the budding yeast Sog2, which is a component of the RAM network (regulation of Ace2 activity and cellular morphogenesis). Lrp1 was essential for both cell growth and cell morphogenesis as were the other MOR components. Lrp1 was localized to the SPBs (spindle pole bodies, the yeast equivalent of the animal centrosome) throughout the cell cycle and to the medial ring during cytokinesis. Lrp1 interacted with Nak1 and was important for Orb6 kinase activity. Thus Lrp1 proved to function upstream of Orb6 in cell morphogenesis.

  12. Evolution of vertebrate colour vision.

    PubMed

    Jacobs, Gerald H; Rowe, Mickey P

    2004-07-01

    Recent years have witnessed a growing interest in learning how colour vision has evolved. This trend has been fuelled by an enhanced understanding of the nature and extent of colour vision among contemporary species, by a deeper understanding of the paleontological record and by the application of new tools from molecular biology. This review provides an assessment of the progress in understanding the evolution of vertebrate colour vision. In so doing, we offer accounts of the evolution of three classes of mechanism important for colour vision--photopigment opsins, oil droplets and retinal organisation--and then examine details of how colour vision has evolved among mammals and, more specifically, among primates.

  13. Evolution of vertebrate visual pigments.

    PubMed

    Bowmaker, James K

    2008-09-01

    The visual pigments of vertebrates evolved about 500 million years ago, before the major evolutionary step of the development of jaws. Four spectrally distinct classes of cone opsin evolved through gene duplication, followed by the rod opsin class that arose from the duplication of the middle-wave-sensitive cone opsin. All four cone classes are present in many extant teleost fish, reptiles and birds, but one or more classes have been lost in primitive fish, amphibians and mammals. Gene duplication within the cone classes, especially in teleosts, has resulted in multiple opsins being available, both temporally and spatially, during development.

  14. Early steps in vertebrate cardiogenesis.

    PubMed

    Mohun, T; Sparrow, D

    1997-10-01

    Heart formation provides an excellent model for studying the molecular basis of cell determination in vertebrate embryos. By combining molecular assays with the experimental approaches of classic embryology, a model for the cell signalling events that initiate cardiogenesis is emerging. Studies of chick, amphibian, and fish embryos demonstrate the inductive role of dorso-anterior endoderm in specifying the cardiac fate of adjacent mesoderm. A consequence of this signalling is the onset of cardiomyogenesis and several transcription factors--Nkx2-5-related, HAND, GATA and MEF-2 families--contribute to these events.

  15. 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.

  16. Structural and functional characterization of oversulfated chondroitin sulfate/dermatan sulfate hybrid chains from the notochord of hagfish. Neuritogenic and binding activities for growth factors and neurotrophic factors.

    PubMed

    Nandini, Chilkunda D; Mikami, Tadahisa; Ohta, Mitsuhiro; Itoh, Nobuyuki; Akiyama-Nambu, Fumiko; Sugahara, Kazuyuki

    2004-12-03

    Oversulfated chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains were purified from the notochord of hagfish. The chains (previously named CS-H for hagfish) have an average molecular mass of 18 kDa. Composition analysis using various chondroitinases demonstrated a variety of D-glucuronic acid (GlcUA)- and L-iduronic acid (IdoUA)-containing disaccharides variably sulfated with a higher proportion of GlcUA/IdoUA-GalNAc 4,6-O-disulfate, revealing complex CS/DS hybrid features. The hybrid chains showed neurite outgrowth-promoting activity of an axonic nature, which resembled the activity of squid cartilage CS-E and which was abolished fully by chondroitinase ABC digestion and partially by chondroitinase AC-I or B digestion, suggesting the involvement of both GlcUA and IdoUA in neuritogenic activity. Purified CS-H exhibited interactions in a BIAcore system with various heparin-binding proteins and neurotrophic factors (viz. fibroblast growth factor-2, -10, -16, and -18; midkine; pleiotrophin; heparin-binding epidermal growth factor-like growth factor; vascular endothelial growth factor; brain-derived neurotrophic factor; and glial cell line-derived neurotrophic factor), most of which are expressed in the brain, although fibroblast growth factor-1 and ciliary neurotrophic factor showed no binding. Kinetic analysis revealed high affinity binding of these growth factors and, for the first time, of the neurotrophic factors. Competitive inhibition revealed the involvement of both IdoUA and GlcUA in the binding of these growth factors, suggesting the importance of the hybrid nature of CS-H for the efficient binding of these growth factors. These findings, together with those from the recent analysis of brain CS/DS chains from neonatal mouse and embryonic pig (Bao, X., Nishimura, S., Mikami, T., Yamada, S., Itoh, N., and Sugahara, K. (2004) J. Biol. Chem. 279, 9765-9776), suggest physiological roles of the hybrid chains in the development of the brain.

  17. Differentiation in microgravity of neural and muscle cells of a vertebrate (amphibian)

    NASA Astrophysics Data System (ADS)

    Husson, D.; Gualandris-Parisot, L.; Foulquier, F.; Grinfield, S.; Kan, P.; Duprat, A.-M.

    The CELIMENE space experiment (CELulles en Impesanteur: Muscle Et Neurone Embryonnaires) was devoted to the study of the influence of gravity on the differentiation, the organisation and the maintenance of the highly specialised nervous system and muscular system. CELIMENE was carried out during the first flight of the IBIS hardware (Instrument for BIology in Space) with the fully automatic space mission PHOTON 10 in February 1995. Using the amphibian Pleurodeles waltl as a vertebrate model, in vitro experiments involved immunocytochemical detection of glial-, neuronal- and muscle-specific markers, and neurotransmitters in cells developed under conditions of microgravity compared with 1g controls, on-board and on the ground. We observed that the altered gravity did not disturb cell morphogenesis or differentiation.

  18. Differentiation in microgravity of neural and muscle cells of a vertebrate (amphibian).

    PubMed

    Husson, D; Gualandris-Parisot, L; Foulquier, F; Grinfield, S; Kan, P; Duprat, A M

    1998-01-01

    The CELIMENE space experiment (CELulles en Impesanteur: Muscle Et Neurone Embryonnaires) was devoted to the study of the influence of gravity on the differentiation, the organisation and the maintenance of the highly specialised nervous system and muscular system. CELIMENE was carried out during the first flight of the IBIS hardware (Instrument for BIology in Space) with the fully automatic space mission PHOTON 10 in February 1995. Using the amphibian Pleurodeles waltl as a vertebrate model, in vitro experiments involved immunocytochemical detection of glial-, neuronal- and muscle-specific markers, and neurotransmitters in cells developed under conditions of microgravity compared with 1g controls, on-board and on the ground. We observed that the altered gravity did not disturb cell morphogenesis or differentiation.

  19. [Spontaneous vertebral arteriovenous fistula manifestating as radiculopathy].

    PubMed

    Ito, Osamu; Nishimura, Ataru; Ishido, Katsuya; Hitotsumatsu, Tsutomu

    2011-08-01

    A 61-year-old man presented with a rare case of spontaneous vertebral arteriovenous fistula manifesting as radiculopathy of the left arm. MRI demonstrated an abnormal dilated vascular space on the left ventral aspect of the spinal canal and compression of the spinal cord and subarachnoid space. MRA disclosed a single high-flow vertebral arteriovenous fistula. Angiography showed a direct high-flow fistula at the C2-3 level between the left vertebral artery and the spinal extradural veinous plexus, and an abnormal dilated left vertebral artery with "string of beads"-like feature. The fistula was successfully obliterated by coil embolization with preservation of patency of the left vertebral artery, resulting in improvement of the signs and symptoms. Retrospectively this spontaneous vertebral arteriovenous fistula was considered in association with fibromuscular dysplasia.

  20. 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.

  1. Evolutionary Specialization of Tactile Perception in Vertebrates

    PubMed Central

    Schneider, Eve R.

    2016-01-01

    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. PMID:27053733

  2. Endocrine disruption in aquatic vertebrates.

    PubMed

    Kloas, Werner; Urbatzka, Ralph; Opitz, Robert; Würtz, Sven; Behrends, Thomas; Hermelink, Björn; Hofmann, Frauke; Jagnytsch, Oana; Kroupova, Hana; Lorenz, Claudia; Neumann, Nadja; Pietsch, Constanze; Trubiroha, Achim; Van Ballegooy, Christoph; Wiedemann, Caterina; Lutz, Ilka

    2009-04-01

    Environmental compounds can interfere with endocrine systems of wildlife and humans. The main sink of such substances, called endocrine disrupters (ED), are surface waters. Thus, aquatic vertebrates, such as fish and amphibians, are most endangered. ED can adversely affect reproductive biology and the thyroid system. ED act by (anti)estrogenic and (anti)androgenic modes of action, resulting in abnormal sexual differentiation and impaired reproduction. These effects are mainly driven by direct interferences of ED with sex steroid receptors rather than indirectly by impacting synthesis and bioavailability of sex steroids, which in turn might affect the hypothalamic-pituitary-gonadal axis. Recent findings reveal that, in addition to the human-produced waste of ED, natural sources, such as parasites and decomposition of leaves, also might act as ED, markedly affecting sexual differentiation and reproduction in fish and amphibians. Although the thyroid system has essential functions in both fish and amphibians, amphibian metamorphosis has been introduced as the most sensitive model to detect thyroidal ED; no suitable fish model exists. Whereas ED may act primarily on only one specific endocrine target, all endocrine systems will eventually be deregulated as they are intimately connected to each other. The recent ecotoxicological issue of pharmaceutically active compounds (PhACs) present in the aquatic environment indicates a high potential for further endocrine modes of action on aquatic vertebrates by ED derived from PhACs, such as glucocorticoids, progestins, and beta-agonists.

  3. Vertebral osteomyelitis: assessment using MR.

    PubMed

    Modic, M T; Feiglin, D H; Piraino, D W; Boumphrey, F; Weinstein, M A; Duchesneau, P M; Rehm, S

    1985-10-01

    Thirty-seven patients who were clinically suspected of having vertebral osteomyelitis were prospectively evaluated with magnetic resonance (MR), radiography, and radionuclide studies. These findings were correlated with the final clinical, microbiologic, or histologic diagnoses. Based on the results of these latter studies, 23 patients were believed to have osteomyelitis. MR examinations consisted of at least a sagittal image (TE = 30 msec, TR = 0.5 sec) and an image obtained at TE = 120 msec, TR = 2-3 sec. All patients underwent radiographic and MR examinations, 36 underwent technetium 99m-HDP bone scanning, and 20 patients underwent gallium 67 scanning. Nineteen patients underwent both bone and gallium scanning. The imaging studies were reviewed independently by investigators blinded to the final diagnoses. MR had a sensitivity of 96%, specificity of 92%, and accuracy of 94%. Combined gallium and bone scan studies (19 cases) had a sensitivity of 90%, specificity of 100%, and accuracy of 94%. Bone scans alone had a sensitivity of 90%, specificity of 78%, and accuracy of 86%. Plain radiographs had a sensitivity of 82%, specificity of 57%, and accuracy of 73%. The MR appearance of vertebral osteomyelitis in this study was characteristic, and MR was as accurate and sensitive as radionuclide scanning in the detection of osteomyelitis.

  4. Pph13 and orthodenticle define a dual regulatory pathway for photoreceptor cell morphogenesis and function.

    PubMed

    Mishra, Monalisa; Oke, Ashwini; Lebel, Cindy; McDonald, Elizabeth C; Plummer, Zachary; Cook, Tiffany A; Zelhof, Andrew C

    2010-09-01

    The function and integrity of photoreceptor cells are dependent upon the creation and maintenance of specialized apical structures: membrane discs/outer segments in vertebrates and rhabdomeres in insects. We performed a molecular and morphological comparison of Drosophila Pph13 and orthodenticle (otd) mutants to investigate the transcriptional network controlling the late stages of rhabdomeric photoreceptor cell development and function. Although Otd and Pph13 have been implicated in rhabdomere morphogenesis, we demonstrate that it is necessary to remove both factors to completely eliminate rhabdomere formation. Rhabdomere absence is not the result of degeneration or a failure of initiation, but rather the inability of the apical membrane to transform and elaborate into a rhabdomere. Transcriptional profiling revealed that Pph13 plays an integral role in promoting rhabdomeric photoreceptor cell function. Pph13 regulates Rh2 and Rh6, and other phototransduction genes, demonstrating that Pph13 and Otd control a distinct subset of Rhodopsin-encoding genes in adult visual systems. Bioinformatic, DNA binding and transcriptional reporter assays showed that Pph13 can bind and activate transcription via a perfect Pax6 homeodomain palindromic binding site and the Rhodopsin core sequence I (RCSI) found upstream of Drosophila Rhodopsin genes. In vivo studies indicate that Pph13 is necessary and sufficient to mediate the expression of a multimerized RCSI reporter, a marker of photoreceptor cell specificity previously suggested to be regulated by Pax6. Our studies define a key transcriptional regulatory pathway that is necessary for late Drosophila photoreceptor development and will serve as a basis for better understanding rhabdomeric photoreceptor cell development and function.

  5. Ghrelin Receptors in Non-Mammalian Vertebrates

    PubMed Central

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2012-01-01

    The growth hormone secretagogue-receptor (GHS-R) was discovered in humans and pigs in 1996. The endogenous ligand, ghrelin, was discovered 3 years later, in 1999, and our understanding of the physiological significance of the ghrelin system in vertebrates has grown steadily since then. Although the ghrelin system in non-mammalian vertebrates is a subject of great interest, protein sequence data for the receptor in non-mammalian vertebrates has been limited until recently, and related biological information has not been well organized. In this review, we summarize current information related to the ghrelin receptor in non-mammalian vertebrates. PMID:23882259

  6. Quorum sensing controls flagellar morphogenesis in Burkholderia glumae.

    PubMed

    Jang, Moon Sun; Goo, Eunhye; An, Jae Hyung; Kim, Jinwoo; Hwang, Ingyu

    2014-01-01

    Burkholderia glumae is a motile plant pathogenic bacterium that has multiple polar flagella and one LuxR/LuxI-type quorum sensing (QS) system, TofR/TofI. A QS-dependent transcriptional regulator, QsmR, activates flagellar master regulator flhDC genes. FlhDC subsequently activates flagellar gene expression in B. glumae at 37°C. Here, we confirm that the interplay between QS and temperature is critical for normal polar flagellar morphogenesis in B. glumae. In the wild-type bacterium, flagellar gene expression and flagellar number were greater at 28°C compared to 37°C. The QS-dependent flhC gene was significantly expressed at 28°C in two QS-defective (tofI::Ω and qsmR::Ω) mutants. Thus, flagella were present in both tofI::Ω and qsmR::Ω mutants at 28°C, but were absent at 37°C. Most tofI::Ω and qsmR::Ω mutant cells possessed polar or nonpolar flagella at 28°C. Nonpolarly flagellated cells processing flagella around cell surface of both tofI::Ω and qsmR::Ω mutants exhibited tumbling and spinning movements. The flhF gene encoding GTPase involved in regulating the correct placement of flagella in other bacteria was expressed in QS mutants in a FlhDC-dependent manner at 28°C. However, FlhF was mislocalized in QS mutants, and was associated with nonpolar flagellar formation in QS mutants at 28°C. These results indicate that QS-independent expression of flagellar genes at 28°C allows flagellar biogenesis, but is not sufficient for normal polar flagellar morphogenesis in B. glumae. Our findings demonstrate that QS functions together with temperature to control flagellar morphogenesis in B. glumae.

  7. Quorum Sensing Controls Flagellar Morphogenesis in Burkholderia glumae

    PubMed Central

    Jang, Moon Sun; Goo, Eunhye; An, Jae Hyung; Kim, Jinwoo; Hwang, Ingyu

    2014-01-01

    Burkholderia glumae is a motile plant pathogenic bacterium that has multiple polar flagella and one LuxR/LuxI-type quorum sensing (QS) system, TofR/TofI. A QS-dependent transcriptional regulator, QsmR, activates flagellar master regulator flhDC genes. FlhDC subsequently activates flagellar gene expression in B. glumae at 37°C. Here, we confirm that the interplay between QS and temperature is critical for normal polar flagellar morphogenesis in B. glumae. In the wild-type bacterium, flagellar gene expression and flagellar number were greater at 28°C compared to 37°C. The QS-dependent flhC gene was significantly expressed at 28°C in two QS-defective (tofI::Ω and qsmR::Ω) mutants. Thus, flagella were present in both tofI::Ω and qsmR::Ω mutants at 28°C, but were absent at 37°C. Most tofI::Ω and qsmR::Ω mutant cells possessed polar or nonpolar flagella at 28°C. Nonpolarly flagellated cells processing flagella around cell surface of both tofI::Ω and qsmR::Ω mutants exhibited tumbling and spinning movements. The flhF gene encoding GTPase involved in regulating the correct placement of flagella in other bacteria was expressed in QS mutants in a FlhDC-dependent manner at 28°C. However, FlhF was mislocalized in QS mutants, and was associated with nonpolar flagellar formation in QS mutants at 28°C. These results indicate that QS-independent expression of flagellar genes at 28°C allows flagellar biogenesis, but is not sufficient for normal polar flagellar morphogenesis in B. glumae. Our findings demonstrate that QS functions together with temperature to control flagellar morphogenesis in B. glumae. PMID:24416296

  8. A Chick Embryo in-Vitro Model of Knee Morphogenesis

    PubMed Central

    Rodriguez, Edward K.; Munasinghe, Jeeva

    2016-01-01

    Background: In this feasibility study, a mechanically loaded in-vitro tissue culture model of joint morphogenesis using the isolated lower extremity of the 8 day old chick embryo was developed to assess the effects of mechanical loading on joint morphogenesis. Methods: The developed in-vitro system allows controlled flexion and extension of the chick embryonic knee with a range of motion of 20 degrees from a resting position of 90-100 degrees of flexion. Joint morphogenesis at 2, 3, 4 and 7 days of culture was assessed by histology and micro MRI in 4 specimen types: undisturbed in-ovo control embryos, in-ovo paralyzed embryos, in-vitro unloaded limb cultures, and in-vitro loaded limb cultures. Relative glycosaminoglycan (GAG) concentration across the joint was assessed with an MRI technique referred to as dGEMRIC (delayed gadolinium enhanced MRI of cartilage) where T1 is proportional to glycosaminoglycan concentration. Results: Average T1 over the entire tissue image for the normal control (IC) knee was 480 msec; for the 4 day loaded specimen average T1 was 354 msec; and for the 7 day loaded specimens T1 was 393 msec. The 4 day unloaded specimen had an average T1 of 279 msec while the 7 day unloaded specimen had an average T1 of 224 msec. The higher T1 values in loaded than unloaded specimens suggest that more glycosaminoglycan is produced in the loaded culture than in the unloaded preparation. Conclusion: Isolated limb tissue cultures under flexion-extension load can be viable and exhibit more progression of joint differentiation and glycosaminoglycan production than similarly cultured but unloaded specimens. However, when compared with controls consisting of intact undisturbed embryos in-ovo, the isolated loaded limbs in culture do not demonstrate equivalent amounts of absolute growth or joint differentiation. PMID:27200386

  9. Modulation of Morphogenesis by Egfr during Dorsal Closure in Drosophila

    PubMed Central

    Cormier, Olga; Cheng, David Chung-Pei; Reed, Bruce; Harden, Nicholas

    2013-01-01

    During Drosophila embryogenesis the process of dorsal closure (DC) results in continuity of the embryonic epidermis, and DC is well recognized as a model system for the analysis of epithelial morphogenesis as well as wound healing. During DC the flanking lateral epidermal sheets stretch, align, and fuse along the dorsal midline, thereby sealing a hole in the epidermis occupied by an extra-embryonic tissue known as the amnioserosa (AS). Successful DC requires the regulation of cell shape change via actomyosin contractility in both the epidermis and the AS, and this involves bidirectional communication between these two tissues. We previously demonstrated that transcriptional regulation of myosin from the zipper (zip) locus in both the epidermis and the AS involves the expression of Ack family tyrosine kinases in the AS in conjunction with Dpp secreted from the epidermis. A major function of Ack in other species, however, involves the negative regulation of Egfr. We have, therefore, asked what role Egfr might play in the regulation of DC. Our studies demonstrate that Egfr is required to negatively regulate epidermal expression of dpp during DC. Interestingly, we also find that Egfr signaling in the AS is required to repress zip expression in both the AS and the epidermis, and this may be generally restrictive to the progression of morphogenesis in these tissues. Consistent with this theme of restricting morphogenesis, it has previously been shown that programmed cell death of the AS is essential for proper DC, and we show that Egfr signaling also functions to inhibit or delay AS programmed cell death. Finally, we present evidence that Ack regulates zip expression by promoting the endocytosis of Egfr in the AS. We propose that the general role of Egfr signaling during DC is that of a braking mechanism on the overall progression of DC. PMID:23579691

  10. Nanopatterned protein microrings from a diatom that direct silica morphogenesis

    PubMed Central

    Scheffel, André; Poulsen, Nicole; Shian, Samuel; Kröger, Nils

    2011-01-01

    Diatoms are eukaryotic microalgae that produce species-specifically structured cell walls made of SiO2 (silica). Formation of the intricate silica structures of diatoms is regarded as a paradigm for biomolecule-controlled self-assembly of three-dimensional, nano- to microscale-patterned inorganic materials. Silica formation involves long-chain polyamines and phosphoproteins (silaffins and silacidins), which are readily soluble in water, and spontaneously form dynamic supramolecular assemblies that accelerate silica deposition and influence silica morphogenesis in vitro. However, synthesis of diatom-like silica structure in vitro has not yet been accomplished, indicating that additional components are required. Here we describe the discovery and intracellular location of six novel proteins (cingulins) that are integral components of a silica-forming organic matrix (microrings) in the diatom Thalassiosira pseudonana. The cingulin-containing microrings are specifically associated with girdle bands, which constitute a substantial part of diatom biosilica. Remarkably, the microrings exhibit protein-based nanopatterns that closely resemble characteristic features of the girdle band silica nanopatterns. Upon the addition of silicic acid the microrings become rapidly mineralized in vitro generating nanopatterned silica replicas of the microring structures. A silica-forming organic matrix with characteristic nanopatterns was also discovered in the diatom Coscinodiscus wailesii, which suggests that preassembled protein-based templates might be general components of the cellular machinery for silica morphogenesis in diatoms. These data provide fundamentally new insight into the molecular mechanisms of biological silica morphogenesis, and may lead to the development of self-assembled 3D mineral forming protein scaffolds with designed nanopatterns for a host of applications in nanotechnology. PMID:21300899

  11. Quantitative vertebral morphometry based on parametric modeling of vertebral bodies in 3D.

    PubMed

    Stern, D; Njagulj, V; Likar, B; Pernuš, F; Vrtovec, T

    2013-04-01

    Quantitative vertebral morphometry (QVM) was performed by parametric modeling of vertebral bodies in three dimensions (3D). Identification of vertebral fractures in two dimensions is a challenging task due to the projective nature of radiographic images and variability in the vertebral shape. By generating detailed 3D anatomical images, computed tomography (CT) enables accurate measurement of vertebral deformations and fractures. A detailed 3D representation of the vertebral body shape is obtained by automatically aligning a parametric 3D model to vertebral bodies in CT images. The parameters of the 3D model describe clinically meaningful morphometric vertebral body features, and QVM in 3D is performed by comparing the parameters to their statistical values. Thresholds and parameters that best discriminate between normal and fractured vertebral bodies are determined by applying statistical classification analysis. The proposed QVM in 3D was applied to 454 normal and 228 fractured vertebral bodies, yielding classification sensitivity of 92.5% at 7.5% specificity, with corresponding accuracy of 92.5% and precision of 86.1%. The 3D shape parameters that provided the best separation between normal and fractured vertebral bodies were the vertebral body height and the inclination and concavity of both vertebral endplates. The described QVM in 3D is able to efficiently and objectively discriminate between normal and fractured vertebral bodies and identify morphological cases (wedge, (bi)concavity, or crush) and grades (1, 2, or 3) of vertebral body fractures. It may be therefore valuable for diagnosing and predicting vertebral fractures in patients who are at risk of osteoporosis.

  12. Salivary Gland Branching Morphogenesis — Recent Progress and Future Opportunities

    PubMed Central

    Hsu, Jeff Chi-feng; Yamada, Kenneth M

    2010-01-01

    Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality-of-life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branching morphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell-cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process. PMID:21125789

  13. Morphogenesis and morphology of HIV. Structure-function relations.

    PubMed

    Gelderblom, H R; Ozel, M; Pauli, G

    1989-01-01

    Fine structure and antigenic make-up analysis of HIV were combined in a 2D model, from which functional aspects can be deduced. On the envelope 72 probably trimeric surface knobs (gp120) are connected to the virion via the transmembrane protein gp41. Gp120 is shed during ageing of the virion, but host cell antigens stay firmly anchored to the envelope. Underneath the envelope, p17 forms the matrix protein layer, while the capsid of the double cone shaped core is built up of p24. The relation between biochemical findings and morphogenesis and maturation of HIV as well as aspects of pathogenesis and vaccination are discussed.

  14. 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.

  15. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis.

    PubMed

    Ewald, Andrew J; Brenot, Audrey; Duong, Myhanh; Chan, Bianca S; Werb, Zena

    2008-04-01

    Epithelial organs are built through the movement of groups of interconnected cells. We observed cells in elongating mammary ducts reorganize into a multilayered epithelium, migrate collectively, and rearrange dynamically, all without forming leading cellular extensions. Duct initiation required proliferation, Rac, and myosin light-chain kinase, whereas repolarization to a bilayer depended on Rho kinase. We observed that branching morphogenesis results from the active motility of both luminal and myoepithelial cells. Luminal epithelial cells advanced collectively, whereas myoepithelial cells appeared to restrain elongating ducts. Significantly, we observed that normal epithelium and neoplastic hyperplasias are organized similarly, suggesting common mechanisms of epithelial growth.

  16. Cortical forces in cell shape changes and tissue morphogenesis.

    PubMed

    Rauzi, Matteo; Lenne, Pierre-François

    2011-01-01

    Cortical forces drive a variety of cell shape changes and cell movements during tissue morphogenesis. While the molecular components underlying these forces have been largely identified, how they assemble and spatially and temporally organize at cell surfaces to promote cell shape changes in developing tissues are open questions. We present here different key aspects of cortical forces: their physical nature, some rules governing their emergence, and how their deployment at cell surfaces drives important morphogenetic movements in epithelia. We review a wide range of literature combining genetic/molecular, biophysical and modeling approaches, which explore essential features of cortical force generation and transmission in tissues.

  17. Cell-to-cell communication in vascular morphogenesis.

    PubMed

    Lehesranta, Satu J; Lichtenberger, Raffael; Helariutta, Ykä

    2010-02-01

    The plant vascular system consists of two conductive cell types, xylem and phloem, which are both produced by procambial cells. Recently, several novel regulatory mechanisms that control the specification of vascular patterning and differentiation have been uncovered. The non-cell-autonomous TDIF/CLE signalling mediates phloem-xylem cross-talk and cambial maintenance; a flowering-related long-distance signal governs secondary development; and novel genetic players such as LHW regulate vascular morphogenesis. A future challenge is to conflate data on the various genetic, hormonal and other factors to understand the networks underlying vascular tissue formation. Copyright 2009 Elsevier Ltd. All rights reserved.

  18. Isolation of an algal morphogenesis inducer from a marine bacterium.

    PubMed

    Matsuo, Yoshihide; Imagawa, Hiroshi; Nishizawa, Mugio; Shizuri, Yoshikazu

    2005-03-11

    Ulva and Enteromorpha are cosmopolitan and familiar marine algal genera. It is well known that these green macroalgae lose their natural morphology during short-term cultivation under aseptic conditions and during long-term cultivation in nutrient-added seawater and adopt an unusual form instead. These phenomena led to the belief that undefined morphogenetic factors that were indispensable to the foliaceous morphology of macroalgae exist throughout the oceans. We characterize a causative factor, named thallusin, isolated from an epiphytic marine bacterium. Thallusin induces normal germination and morphogenesis of green macroalgae.

  19. 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'.

  20. 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'.

  1. 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.

  2. 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)

  3. 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.

  4. 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)

  5. AFR1 acts in conjunction with the alpha-factor receptor to promote morphogenesis and adaptation.

    PubMed Central

    Konopka, J B

    1993-01-01

    Mating pheromone receptors activate a G-protein signaling pathway that induces changes in transcription, cell division, and morphogenesis needed for the conjunction of Saccharomyces cerevisiae. The C terminus of the alpha-factor pheromone receptor functions in two complex processes, adaptation and morphogenesis. Adaptation to alpha-factor may occur through receptor desensitization, and alpha-factor-induced morphogenesis forms the conjugation bridge between mating cells. A plasmid overexpression strategy was used to isolate a new gene, AFR1, which acts together with the receptor C terminus to promote adaptation. The expression of AFR1 was highly induced by alpha-factor. Unexpectedly, cells lacking AFR1 showed a defect in alpha-factor-stimulated morphogenesis that was similar to the morphogenesis defect observed in cells producing C-terminally truncated alpha-factor receptors. In contrast, AFR1 overexpression resulted in longer projections of morphogenesis, which suggests that this gene may directly stimulate morphogenesis. These results indicate that AFR1 encodes a developmentally regulated function that coordinates both the regulation of receptor signaling and the induction of morphogenesis during conjugation. Images PMID:8413281

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

    PubMed

    von Dassow, Michelangelo; Davidson, Lance A

    2011-08-01

    Morphogenesis takes place against a background of organism-to-organism and environmental variation. Therefore, fundamental questions in the study of morphogenesis include: How are the mechanical processes of tissue movement and deformation affected by that variability, and in turn, how do the mechanic of the system modulate 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.

  7. 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

  8. 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.

  9. Spinal cord compression due to vertebral hemangioma.

    PubMed

    Aksu, Gorkem; Fayda, Merdan; Saynak, Mert; Karadeniz, Ahmet

    2008-02-01

    This article presents a case of multiple vertebral hemangiomas in a 58-year-old man with pain in the dorsal region and bilateral progressive foot numbness. Magnetic resonance imaging revealed multiple vertebral hemangiomas. One hemangioma at the T7 level demonstrated epidural extension, causing spinal cord compression. After treatment with radiotherapy, the patient's symptoms improved significantly.

  10. The evolution of adaptive immunity in vertebrates.

    PubMed

    Hirano, Masayuki; Das, Sabyasachi; Guo, Peng; Cooper, Max D

    2011-01-01

    Approximately 500 million years ago, two types of recombinatorial adaptive immune systems (AISs) arose in vertebrates. The jawed vertebrates diversify their repertoire of immunoglobulin domain-based T and B cell antigen receptors mainly through the rearrangement of V(D)J gene segments and somatic hypermutation, but none of the fundamental AIS recognition elements in jawed vertebrates have been found in jawless vertebrates. Instead, the AIS of jawless vertebrates is based on variable lymphocyte receptors (VLRs) that are generated through recombinatorial usage of a large panel of highly diverse leucine-rich-repeat (LRR) sequences. Whereas the appearance of transposon-like, recombination-activating genes contributed uniquely to the origin of the AIS in jawed vertebrates, the use of activation-induced cytidine deaminase for receptor diversification is common to both the jawed and jawless vertebrates. Despite these differences in anticipatory receptor construction, the basic AIS design featuring two interactive T and B lymphocyte arms apparently evolved in an ancestor of jawed and jawless vertebrates within the context of preexisting innate immunity and has been maintained since as a consequence of powerful and enduring selection, most probably for pathogen defense purposes.

  11. Eye marks in vertebrates: AIDS to vision.

    PubMed

    Ficken, R W; Matthiae, P E; Horwich, R

    1971-09-03

    Lines leading forward from the eye may function as aiming sights in many small vertebrates. The chief evidence is the correlation of distribution and positions of eye-lines in various vertebrate groups with predatory feeding habits. Dark patches around the eye may serve to reduce glare in species in bright environments. Facial patterns often have multiple functions.

  12. Vertebral osteomyelitis in insulin-dependent diabetics.

    PubMed

    Cooppan, R; Schoenbaum, S; Younger, M D; Freidberg, S; D'elia, J

    1976-11-20

    Vertebral osteomyelitis continues to be a diagnostically and therapeutically challenging disease with a relatively high incidence in diabetics. The clinical features, investigations and treatment of 7 insulin-dependent diabetics with vertebral osteomyelitis are presented and possible aetiological factors in this group are discussed.

  13. Generative rules for the morphogenesis of epithelial tubes.

    PubMed

    Beloussov, L V; Lakirev, A V

    1991-10-21

    A finite elements model imitating the morphogenesis of smoothly curved tubular epithelial rudiments is suggested. It is based upon the experimentally proved assumption of the lateral (tangential) pressure between adjacent epithelial cells. The main idea of the model is that under a non-zero local curvature the lateral cell-cell pressure acquires the radial components which are absent under zero curvature. In the framework of the model we investigate the roles of initial geometry, the different coefficients relating the local curvatures and radial cell shifts, and of visco-elastical cell-cell linkages in the shaping process. We also employ the different temporal regimes (both periodical and constant) of the lateral pressure exerted and the different overall durations of the modelling. As a result, we get a set of biologically realistical shapes, almost all of them belonging to the same basical "trefoiled" archetype. Among the variables explored, shaping was most affected by the changes in visco-elastical coefficients, in the temporal regimes and in the overall duration of the modelling. The model shows that rather complicated and realistical shapes of epithelial rudiments can be obtained without assuming any initial regional differences inside cell layers. The model may be useful for understanding the principles underlying both genetical and epigenetical regulation of the morphogenesis.

  14. Size-dependent symmetry breaking in models for morphogenesis

    NASA Astrophysics Data System (ADS)

    Barrio, R. A.; Maini, P. K.; Aragón, J. L.; Torres, M.

    2002-08-01

    A general property of dynamical systems is the appearance of spatial and temporal patterns due to a change of stability of a homogeneous steady state. Such spontaneous symmetry breaking is observed very frequently in all kinds of real systems, including the development of shape in living organisms. Many nonlinear dynamical systems present a wide variety of patterns with different shapes and symmetries. This fact restricts the applicability of these models to morphogenesis, since one often finds a surprisingly small variation in the shapes of living organisms. For instance, all individuals in the Phylum Echinodermata share a persistent radial fivefold symmetry. In this paper, we investigate in detail the symmetry-breaking properties of a Turing reaction-diffusion system confined in a small disk in two dimensions. It is shown that the symmetry of the resulting pattern depends only on the size of the disk, regardless of the boundary conditions and of the differences in the parameters that differentiate the interior of the domain from the outer space. This study suggests that additional regulatory mechanisms to control the size of the system are of crucial importance in morphogenesis.

  15. 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

  16. Ultrastructural and biochemical basis for hepatitis C virus morphogenesis.

    PubMed

    Falcón, Viviana; Acosta-Rivero, Nelson; González, Sirenia; Dueñas-Carrera, Santiago; Martinez-Donato, Gillian; Menéndez, Ivon; Garateix, Rocio; Silva, José A; Acosta, Emilio; Kourı, Juan

    2017-04-01

    Chronic infection with HCV is a leading cause of cirrhosis, hepatocellular carcinoma and liver failure. One of the least understood steps in the HCV life cycle is the morphogenesis of new viral particles. HCV infection alters the lipid metabolism and generates a variety of microenvironments in the cell cytoplasm that protect viral proteins and RNA promoting viral replication and assembly. Lipid droplets (LDs) have been proposed to link viral RNA synthesis and virion assembly by physically associating these viral processes. HCV assembly, envelopment, and maturation have been shown to take place at specialized detergent-resistant membranes in the ER, rich in cholesterol and sphingolipids, supporting the synthesis of luminal LDs-containing ApoE. HCV assembly involves a regulated allocation of viral and host factors to viral assembly sites. Then, virus budding takes place through encapsidation of the HCV genome and viral envelopment in the ER. Interaction of ApoE with envelope proteins supports the viral particle acquisition of lipids and maturation. HCV secretion has been suggested to entail the ion channel activity of viral p7, several components of the classical trafficking and autophagy pathways, ESCRT, and exosome-mediated export of viral RNA. Here, we review the most recent advances in virus morphogenesis and the interplay between viral and host factors required for the formation of HCV virions.

  17. 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.

  18. Dkk1 regulates ventral midbrain dopaminergic differentiation and morphogenesis.

    PubMed

    Ribeiro, Diogo; Ellwanger, Kristina; Glagow, Désirée; Theofilopoulos, Spyridon; Corsini, Nina S; Martin-Villalba, Ana; Niehrs, Christof; Arenas, Ernest

    2011-02-11

    Dickkopf1 (Dkk1) is a Wnt/β-catenin inhibitor that participates in many processes during embryonic development. One of its roles during embryogenesis is to induce head formation, since Dkk1-null mice lack head structures anterior to midbrain. The Wnt/β-catenin pathway is also known to regulate different aspects of ventral midbrain (VM) dopaminergic (DA) neuron development and, in vitro, Dkk1-mediated inhibition of the Wnt/β-catenin pathway improves the DA differentiation in mouse embryonic stem cells (mESC). However, the in vivo function of Dkk1 on the development of midbrain DA neurons remains to be elucidated. Here we examined Dkk1(+/-) embryos and found that Dkk1 is required for the differentiation of DA precursors/neuroblasts into DA neurons at E13.5. This deficit persisted until E17.5, when a defect in the number and distribution of VM DA neurons was detected. Furthermore, analysis of the few Dkk1(-/-) embryos that survived until E17.5 revealed a more severe loss of midbrain DA neurons and morphogenesis defects. Our results thus show that Dkk1 is required for midbrain DA differentiation and morphogenesis.

  19. Morphogenesis of callosal arbors in the parietal cortex of hamsters.

    PubMed

    Hedin-Pereira, C; Lent, R; Jhaveri, S

    1999-01-01

    The morphogenesis of callosal axons originating in the parietal cortex was studied by anterograde labeling with Phaseolus lectin or biocytin injected in postnatal (P) hamsters aged 7-25 days. Some labeled fibers were serially reconstructed. At P7, some callosal fibers extended as far as the contralateral rhinal fissure, with simple arbors located in the homotopic region of the opposite cortical gray matter, and two or three unbranched sprouts along their trajectory. From P7 to P13, the homotopic arbors became more complex, with branches focused predominantly, but not exclusively, in the supra- and infragranular layers of the homotopic region. Simultaneously, the lateral extension of the trunk axon in the white matter became shorter, finally disappearing by P25. Arbors in the gray matter were either bilaminar (layers 2/3 and 5) or supragranular. A heterotopic projection to the lateral cortex was consistently seen at all ages; the heterotopic arbors follow a similar sequence of events to that seen in homotopic regions. These observations document that callosal axons undergo regressive tangential remodeling during the first postnatal month, as the lateral extension of the trunk fiber gets eliminated. Radially, however, significant arborization occurs in layer-specific locations. The protracted period of morphogenesis suggests a correspondingly long plastic period for this system of cortical fibers.

  20. A simple probabilistic model of submicroscopic diatom morphogenesis

    PubMed Central

    Willis, L.; Cox, E. J.; Duke, T.

    2013-01-01

    Unicellular algae called diatoms morph biomineral compounds into tough exoskeletons via complex intracellular processes about which there is much to be learned. These exoskeletons feature a rich variety of structures from submicroscale to milliscale, many that have not been reproduced in vitro. In order to help understand this complex miniature morphogenesis, here we introduce and analyse a simple model of biomineral kinetics, focusing on the exoskeleton's submicroscopic patterned planar structures called pore occlusions. The model reproduces most features of these pore occlusions by retuning just one parameter, thereby indicating what physio-biochemical mechanisms could sufficiently explain morphogenesis at the submicroscopic scale: it is sufficient to identify a mechanism of lateral negative feedback on the biomineral reaction kinetics. The model is nonlinear and stochastic; it is an extended version of the threshold voter model. Its mean-field equation provides a simple and, as far as the authors are aware, new way of mapping out the spatial patterns produced by lateral inhibition and variants thereof. PMID:23554345

  1. Mathematical model of the morphogenesis checkpoint in budding yeast

    PubMed Central

    Ciliberto, Andrea; Novak, Bela; Tyson, John J.

    2003-01-01

    The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast. The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, converted into a set of differential equations and studied by numerical simulation. The simulations accurately reproduce the phenotypes of a dozen checkpoint mutants. Among other predictions, the model attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation: Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity. The model supports the idea that the morphogenesis checkpoint, like other checkpoints, raises the cell size threshold for progression from one phase of the cell cycle to the next. PMID:14691135

  2. Mathematical model of the morphogenesis checkpoint in budding yeast.

    PubMed

    Ciliberto, Andrea; Novak, Bela; Tyson, John J

    2003-12-22

    The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. We propose a molecular network for Swe1 control, based on published observations of budding yeast and analogous control signals in fission yeast. The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, converted into a set of differential equations and studied by numerical simulation. The simulations accurately reproduce the phenotypes of a dozen checkpoint mutants. Among other predictions, the model attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation: Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity. The model supports the idea that the morphogenesis checkpoint, like other checkpoints, raises the cell size threshold for progression from one phase of the cell cycle to the next.

  3. 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.

  4. Early epithelial signaling center governs tooth budding morphogenesis

    PubMed Central

    Thesleff, Irma

    2016-01-01

    During organogenesis, cell fate specification and patterning are regulated by signaling centers, specialized clusters of morphogen-expressing cells. In many organs, initiation of development is marked by bud formation, but the cellular mechanisms involved are ill defined. Here, we use the mouse incisor tooth as a model to study budding morphogenesis. We show that a group of nonproliferative epithelial cells emerges in the early tooth primordium and identify these cells as a signaling center. Confocal live imaging of tissue explants revealed that although these cells reorganize dynamically, they do not reenter the cell cycle or contribute to the growing tooth bud. Instead, budding is driven by proliferation of the neighboring cells. We demonstrate that the activity of the ectodysplasin/Edar/nuclear factor κB pathway is restricted to the signaling center, and its inactivation leads to fewer quiescent cells and a smaller bud. These data functionally link the signaling center size to organ size and imply that the early signaling center is a prerequisite for budding morphogenesis. PMID:27621364

  5. Genomic Regions Required for Morphogenesis of the Drosophila Embryonic Midgut

    PubMed Central

    Bilder, D.; Scott, M. P.

    1995-01-01

    The Drosophila midgut is an excellent system for studying the cell migration, cell-cell communication, and morphogenetic events that occur in organ formation. Genes representative of regulatory gene families common to all animals, including homeotic, TGFβ, and Wnt genes, play roles in midgut development. To find additional regulators of midgut morphogenesis, we screened a set of genomic deficiencies for midgut phenotypes. Fifteen genomic intervals necessary for proper midgut morphogenesis were identified; three contain genes already known to act in the midgut. Three other genomic regions are required for formation of the endoderm or visceral mesoderm components of the midgut. Nine regions are required for proper formation of the midgut constrictions. The E75 ecdysone-induced gene, which encodes a nuclear receptor superfamily member, is the relevant gene in one region and is essential for proper formation of midgut constrictions. E75 acts downstream of the previously known constriction regulators or in parallel. Temporal hormonal control may therefore work in conjunction with spatial regulation by the homeotic genes in midgut development. Another genomic region is required to activate transcription of the homeotic genes Antp and Scr specifically in visceral mesoderm. The genomic regions identified by this screen provide a map to novel midgut development regulators. PMID:8582615

  6. PARP6 is a Regulator of Hippocampal Dendritic Morphogenesis

    PubMed Central

    Huang, Jeffrey Y.; Wang, Kang; Vermehren-Schmaedick, Anke; Adelman, John P.; Cohen, Michael S.

    2016-01-01

    Mono-ADP-ribosylation (MARylation) of mammalian proteins was first described as a post-translational modification catalyzed by bacterial toxins. It is now known that endogenous MARylation occurs in mammalian cells and is catalyzed by 11 members of the poly-ADP-ribose polymerase (PARP) family of proteins (17 in humans). The physiological roles of these PARPs remain largely unknown. Here we demonstrate that PARP6, a neuronally enriched PARP that catalyzes MARylation, regulates hippocampal dendrite morphogenesis, a process that is critical for proper neural circuit formation during development. Knockdown of PARP6 significantly decreased dendritic complexity in embryonic rat hippocampal neurons in culture and in vivo. Expression of wild-type PARP6 increased dendritic complexity; conversely, expression of a catalytically inactive PARP6 mutant, or a cysteine-rich domain deletion mutant that has significantly reduced catalytic activity, decreased dendritic complexity. The identification of PARP6 as a regulator of dendrite morphogenesis supports a role for MARylation in neurons during development. PMID:26725726

  7. 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.

  8. Tribolium embryo morphogenesis: may the force be with you.

    PubMed

    Benton, Matthew A; Pavlopoulos, Anastasios

    2014-01-01

    Development of multicellular organisms depends on patterning and growth mechanisms encoded in the genome, but also on the physical properties and mechanical interactions of the constituent cells that interpret these genetic cues. This fundamental biological problem requires integrated studies at multiple levels of biological organization: from genes, to cell behaviors, to tissue morphogenesis. We have recently combined functional genetics with live imaging approaches in embryos of the insect Tribolium castaneum, in order to understand their remarkable transformation from a uniform single-layered blastoderm into a condensed multi-layered embryo covered by extensive extra-embryonic tissues. We first developed a quick and reliable methodology to fluorescently label various cell components in entire Tribolium embryos. Live imaging of labeled embryos at single cell resolution provided detailed descriptions of cell behaviors and tissue movements during normal embryogenesis. We then compared cell and tissue dynamics between wild-type and genetically perturbed embryos that exhibited altered relative proportions of constituent tissues. This systematic comparison led to a qualitative model of the molecular, cellular and tissue interactions that orchestrate the observed epithelial rearrangements. We expect this work to establish the Tribolium embryo as a powerful and attractive model system for biologists and biophysicists interested in the molecular, cellular and mechanical control of tissue morphogenesis.

  9. Lamprey: a model for vertebrate evolutionary research.

    PubMed

    Xu, Yang; Zhu, Si-Wei; Li, Qing-Wei

    2016-09-18

    Lampreys belong to the superclass Cyclostomata and represent the most ancient group of vertebrates. Existing for over 360 million years, they are known as living fossils due to their many evolutionally conserved features. They are not only a keystone species for studying the origin and evolution of vertebrates, but also one of the best models for researching vertebrate embryonic development and organ differentiation. From the perspective of genetic information, the lamprey genome remains primitive compared with that of other higher vertebrates, and possesses abundant functional genes. Through scientific and technological progress, scientists have conducted in-depth studies on the nervous, endocrine, and immune systems of lampreys. Such research has significance for understanding and revealing the origin and evolution of vertebrates, and could contribute to a greater understanding of human diseases and treatments. This review presents the current progress and significance of lamprey research.

  10. Lamprey: a model for vertebrate evolutionary research

    PubMed Central

    XU, Yang; ZHU, Si-Wei; LI, Qing-Wei

    2016-01-01

    Lampreys belong to the superclass Cyclostomata and represent the most ancient group of vertebrates. Existing for over 360 million years, they are known as living fossils due to their many evolutionally conserved features. They are not only a keystone species for studying the origin and evolution of vertebrates, but also one of the best models for researching vertebrate embryonic development and organ differentiation. From the perspective of genetic information, the lamprey genome remains primitive compared with that of other higher vertebrates, and possesses abundant functional genes. Through scientific and technological progress, scientists have conducted in-depth studies on the nervous, endocrine, and immune systems of lampreys. Such research has significance for understanding and revealing the origin and evolution of vertebrates, and could contribute to a greater understanding of human diseases and treatments. This review presents the current progress and significance of lamprey research. PMID:27686784

  11. 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

  12. Nanotechnology for treating osteoporotic vertebral fractures.

    PubMed

    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.

  13. 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.

  14. The prevalence of vertebral fracture amongst patients presenting with non-vertebral fractures.

    PubMed

    Gallacher, S J; Gallagher, A P; McQuillian, C; Mitchell, P J; Dixon, T

    2007-02-01

    Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture. Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale. Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50-64 years, 53.2% were aged 65-74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score -1 or above), 37.4% were osteopenic (T-score -1.1 to -2.4) and 27.6% osteoporotic (T-score -2.5 or lower). Humerus (n=103, 31%), radius-ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score vertebral fracture were all significantly more likely to have evidence of a prevalent vertebral deformity (p<0.05). However, 19.8% of patients with an osteopenic T-score had a vertebral deformity (48% of which were multiple), and 16.1% of patients with a normal T-score had a vertebral deformity (26.3% of which were multiple). Following non-vertebral fracture, some

  15. Mitotic chromosome condensation in vertebrates

    SciTech Connect

    Vagnarelli, Paola

    2012-07-15

    Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes of

  16. Ethnic difference of clinical vertebral fracture risk.

    PubMed

    Bow, C H; Cheung, E; Cheung, C L; Xiao, S M; Loong, C; Soong, C; Tan, K C; Luckey, M M; Cauley, J A; Fujiwara, S; Kung, A W C

    2012-03-01

    Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate. Vertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups. Four thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations. The mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical

  17. Two Rare Variants of Left Vertebral Artery.

    PubMed

    Singh, Rajani

    2017-02-15

    Though the variations of vertebral artery are clinically asymptomatic yet abnormalities are of diagnostic importance either prior to vascular surgery in the neck region or in patients of intravascular diseases such as arteriovenous malformations or cerebral aneurysms. Therefore, the aim of the study is to bring out 2 variations in the configuration of vertebral artery and their clinical implication. During dissection of thorax of 2 female cadavers, 2 different variants of configurations of left vertebral arteries were observed. In 1 patient, the left vertebral artery arose aberrantly from arch of aorta between left common carotid artery and left subclavian artery. This artery then, following oblique course, abnormally entered into foramen transversarium of C4 vertebra. In the second patient, the left common stump emerged from arch of aorta in the left side of left common carotid artery and then instantly bifurcated into vertebral artery and subclavian artery. Then following the usual oblique course, the left vertebral artery anomalously entered into foramen transversarium of C3 vertebra at the level of upper border of thyroid cartilage. The knowledge of these rare variations in the origin of vertebral artery is of paramount importance to surgeons performing surgery in neck region, radiologist performing angiography to avoid misinterpretation of radiographs and to anatomists for rare variations in academics and research.

  18. Control of vertebrate core planar cell polarity protein localization and dynamics by Prickle 2

    PubMed Central

    Butler, Mitchell T.; Wallingford, John B.

    2015-01-01

    Planar cell polarity (PCP) is a ubiquitous property of animal tissues and is essential for morphogenesis and homeostasis. In most cases, this fundamental property is governed by a deeply conserved set of ‘core PCP’ proteins, which includes the transmembrane proteins Van Gogh-like (Vangl) and Frizzled (Fzd), as well as the cytoplasmic effectors Prickle (Pk) and Dishevelled (Dvl). Asymmetric localization of these proteins is thought to be central to their function, and understanding the dynamics of these proteins is an important challenge in developmental biology. Among the processes that are organized by the core PCP proteins is the directional beating of cilia, such as those in the vertebrate node, airway and brain. Here, we exploit the live imaging capabilities of Xenopus to chart the progressive asymmetric localization of fluorescent reporters of Dvl1, Pk2 and Vangl1 in a planar polarized ciliated epithelium. Using this system, we also characterize the influence of Pk2 on the asymmetric dynamics of Vangl1 at the cell cortex, and we define regions of Pk2 that control its own localization and those impacting Vangl1. Finally, our data reveal a striking uncoupling of Vangl1 and Dvl1 asymmetry. This study advances our understanding of conserved PCP protein functions and also establishes a rapid, tractable platform to facilitate future in vivo studies of vertebrate PCP protein dynamics. PMID:26293301

  19. Vangl2 cooperates with Rab11 and Myosin V to regulate apical constriction during vertebrate gastrulation.

    PubMed

    Ossipova, Olga; Chuykin, Ilya; Chu, Chih-Wen; Sokol, Sergei Y

    2015-01-01

    Core planar cell polarity (PCP) proteins are well known to regulate polarity in Drosophila and vertebrate epithelia; however, their functions in vertebrate morphogenesis remain poorly understood. In this study, we describe a role for PCP signaling in the process of apical constriction during Xenopus gastrulation. The core PCP protein Vangl2 is detected at the apical surfaces of cells at the blastopore lip, and it functions during blastopore formation and closure. Further experiments show that Vangl2, as well as Daam1 and Rho-associated kinase (Rock), regulate apical constriction of bottle cells at the blastopore and ectopic constriction of ectoderm cells triggered by the actin-binding protein Shroom3. At the blastopore lip, Vangl2 is required for the apical accumulation of the recycling endosome marker Rab11. We also show that Rab11 and the associated motor protein Myosin V play essential roles in both endogenous and ectopic apical constriction, and might be involved in Vangl2 trafficking to the cell surface. Overexpression of Rab11 RNA was sufficient to partly restore normal blastopore formation in Vangl2-deficient embryos. These observations suggest that Vangl2 affects Rab11 to regulate apical constriction during blastopore formation.

  20. Cadherins and catenins in dendrite and synapse morphogenesis

    PubMed Central

    Seong, Eunju; Yuan, Li; Arikkath, Jyothi

    2015-01-01

    Neurons are highly polarized specialized cells. Neuronal integrity and functional roles are critically dependent on dendritic architecture and synaptic structure, function and plasticity. The cadherins are glycosylated transmembrane proteins that form cell adhesion complexes in various tissues. They are associated with a group of cytosolic proteins, the catenins. While the functional roles of the complex have been extensively investigates in non-neuronal cells, it is becoming increasingly clear that components of the complex have critical roles in regulating dendritic and synaptic architecture, function and plasticity in neurons. Consistent with these functional roles, aberrations in components of the complex have been implicated in a variety of neurodevelopmental disorders. In this review, we discuss the roles of the classical cadherins and catenins in various aspects of dendrite and synapse architecture and function and their relevance to human neurological disorders. Cadherins are glycosylated transmembrane proteins that were initially identified as Ca2+-dependent cell adhesion molecules. They are present on plasma membrane of a variety of cell types from primitive metazoans to humans. In the past several years, it has become clear that in addition to providing mechanical adhesion between cells, cadherins play integral roles in tissue morphogenesis and homeostasis. The cadherin family is composed of more than 100 members and classified into several subfamilies, including classical cadherins and protocadherins. Several of these cadherin family members have been implicated in various aspects of neuronal development and function.1-3 The classical cadherins are associated with a group of cytosolic proteins, collectively called the catenins. While the functional roles of the cadherin-catenin cell adhesion complex have been extensively investigated in epithelial cells, it is now clear that components of the complex are well expressed in central neurons at different

  1. Developmental control of segment numbers in vertebrates

    PubMed Central

    Gomez, Céline; Pourquié, Olivier

    2011-01-01

    Segmentation or metamery in vertebrates is best illustrated by the repetition of the vertebrae and ribs, their associated skeletal muscles and blood vessels, and the spinal nerves and ganglia. The segment number varies tremendously among the different vertebrate species, ranging from as few as six vertebrae in some frogs to as many as several hundred in some snakes and fish. In vertebrates, metameric segments or somites form sequentially during body axis formation. This results in the embryonic axis becoming entirely segmented into metameric units from the level of the otic vesicle almost to the very tip of the tail. The total segment number mostly depends on two parameters: (1) the control of the posterior growth of the body axis during somitogenesis—more same-size segments can be formed in a longer axis and (2) segment size—more smaller-size segments can be formed in a same-size body axis. During evolution, independent variations of these parameters could explain the huge diversity in segment numbers observed among vertebrate species. These variations in segment numbers are accompanied by diversity in the regionalization of the vertebral column. For example, amniotes can exhibit up to five different types of vertebrae: cervical, thoracic, lumbar, sacral and caudal, the number of which varies according to the species. This regionalization of the vertebral column is controlled by the Hox family of transcription factors. We propose that during development, dissociation of the Hox- and segmentation-clock-dependent vertebral patterning systems explains the enormous diversity of vertebral formulae observed in vertebrates. PMID:19621429

  2. [Spasmodic torticollis and vertebral hemangioma].

    PubMed

    Durán, E; Chacón, J R

    Spasmodic torticollis in young patients should give rise to a clinical suspicion that this is secondary to another primary disorder. Therefore a series of diagnostic tests should be carried out before it is labelled as idiopathic. The patient was a thirty year old man who had had difficulty in writing with his right hand since childhood. At the age of 20 years he was diagnosed as having writer's cramp and idiopathic spasmodic torticollis. On general physical examination no abnormalities were found. On neurological examination he had: absence of reflexes of both arms, limited but painless rotation of the neck towards the left and hypertrophy of the left trapezius muscle. Laboratory, neurophysiological and neuroimaging investigations seeking a secondary cause for the torticollis were all normal. There were no Keyser-Fleischer rings. Chest X-ray showed, dorsal scoliosis with convexity to the left. CAT and MR of the spine showed a hemangioma in the body of T1. On arteriography of the supra-aortic and vertebral trunks a hemangioma was found at T1 which received contrast material via a branch of the right thyro-bi-cervico-scapular trunk. Various treatments were tried (diazepam, Botox, Dysport, tetrabenazine, baclofen, etc.) with no improvement. A definite diagnosis of secondary torticollis could not be made since the hemangioma was supplied by a very narrow vascular pedicle, so embolization was contraindicated. Cervical spinal cord alterations may cause focal dystonia due to increased excitability of the spinal motor neurone, due to dysfunction of the disinhibitory descending reciprocal paths.

  3. Rotations in a Vertebrate Setting

    NASA Astrophysics Data System (ADS)

    McCollum, Gin

    2003-05-01

    Rotational movements of the head are often considered to be measured in a single three dimensional coordinate system implemented by the semicircular canals of the vestibular system of the inner ear. However, the vertebrate body -- including the nervous system -- obeys rectangular symmetries alien to rotation groups. At best, nervous systems mimic the physical rotation group in a fragmented way, only partially reintegrating physical movements in whole organism responses. The vestibular canal reference frame is widely used in nervous systems, for example by eye movements. It is used to some extent even in the cerebrum, as evidenced by the remission of hemineglect -- in which half of space is ignored -- when the vestibular system is stimulated. However, reintegration of space by the organism remains incomplete. For example, compensatory eye movements (which in most cases aid visual fixation) may disagree with conscious self-motion perception. In addition, movement-induced nausea, illusions, and cue-free perceptions demonstrate symmetry breaking or incomplete spatial symmetries. As part of a long-term project to investigate rotation groups in nervous systems, we have analyzed the symmetry group of a primary vestibulo-spinal projection.

  4. Antibody Isotype Switching in Vertebrates.

    PubMed

    Senger, Kate; Hackney, Jason; Payandeh, Jian; Zarrin, Ali A

    2015-01-01

    The humoral or antibody-mediated immune response in vertebrates has evolved to respond to diverse antigenic challenges in various anatomical locations. Diversification of the immunoglobulin heavy chain (IgH) constant region via isotype switching allows for remarkable plasticity in the immune response, including versatile tissue distribution, Fc receptor binding, and complement fixation. This enables antibody molecules to exert various biological functions while maintaining antigen-binding specificity. Different immunoglobulin (Ig) classes include IgM, IgD, IgG, IgE, and IgA, which exist as surface-bound and secreted forms. High-affinity autoantibodies are associated with various autoimmune diseases such as lupus and arthritis, while defects in components of isotype switching are associated with infections. A major route of infection used by a large number of pathogens is invasion of mucosal surfaces within the respiratory, digestive, or urinary tract. Most infections of this nature are initially limited by effector mechanisms such as secretory IgA antibodies. Mucosal surfaces have been proposed as a major site for the genesis of adaptive immune responses, not just in fighting infections but also in tolerating commensals and constant dietary antigens. We will discuss the evolution of isotype switching in various species and provide an overview of the function of various isotypes with a focus on IgA, which is universally important in gut homeostasis as well as pathogen clearance. Finally, we will discuss the utility of antibodies as therapeutic modalities.

  5. Vertebral numbers and human evolution.

    PubMed

    Williams, Scott A; Middleton, Emily R; Villamil, Catalina I; Shattuck, Milena R

    2016-01-01

    Ever since Tyson (1699), anatomists have noted and compared differences in the regional numbers of vertebrae among humans and other hominoids. Subsequent workers interpreted these differences in phylogenetic, functional, and behavioral frameworks and speculated on the history of vertebral numbers during human evolution. Even in a modern phylogenetic framework and with greatly expanded sample sizes of hominoid species, researchers' conclusions vary drastically, positing that hominins evolved from either a "long-backed" (numerically long lumbar column) or a "short-backed" (numerically short lumbar column) ancestor. We show that these disparate interpretations are due in part to the use of different criteria for what defines a lumbar vertebra, but argue that, regardless of which lumbar definition is used, hominins are similar to their great ape relatives in possessing a short trunk, a rare occurrence in mammals and one that defines the clade Hominoidea. Furthermore, we address the recent claim that the early hominin thoracolumbar configuration is not distinct from that of modern humans and conclude that early hominins show evidence of "cranial shifting," which might explain the anomalous morphology of several early hominin fossils. Finally, we evaluate the competing hypotheses on numbers of vertebrae and argue that the current data support a hominin ancestor with an African ape-like short trunk and lower back. © 2016 Wiley Periodicals, Inc.

  6. Organizational heterogeneity of vertebrate genomes.

    PubMed

    Frenkel, Svetlana; Kirzhner, Valery; Korol, Abraham

    2012-01-01

    Genomes of higher eukaryotes are mosaics of segments with various structural, functional, and evolutionary properties. The availability of whole-genome sequences allows the investigation of their structure as "texts" using different statistical and computational methods. One such method, referred to as Compositional Spectra (CS) analysis, is based on scoring the occurrences of fixed-length oligonucleotides (k-mers) in the target DNA sequence. CS analysis allows generating species- or region-specific characteristics of the genome, regardless of their length and the presence of coding DNA. In this study, we consider the heterogeneity of vertebrate genomes as a joint effect of regional variation in sequence organization superimposed on the differences in nucleotide composition. We estimated compositional and organizational heterogeneity of genome and chromosome sequences separately and found that both heterogeneity types vary widely among genomes as well as among chromosomes in all investigated taxonomic groups. The high correspondence of heterogeneity scores obtained on three genome fractions, coding, repetitive, and the remaining part of the noncoding DNA (the genome dark matter--GDM) allows the assumption that CS-heterogeneity may have functional relevance to genome regulation. Of special interest for such interpretation is the fact that natural GDM sequences display the highest deviation from the corresponding reshuffled sequences.

  7. Heterogeneity of vertebrate brain tubulins.

    PubMed Central

    Field, D J; Collins, R A; Lee, J C

    1984-01-01

    We have examined the extent of brain tubulin heterogeneity in six vertebrate species commonly used in tubulin research (rat, calf, pig, chicken, human, and lamb) using isoelectric focusing, two-dimensional electrophoresis, and peptide mapping procedures that provide higher resolution than previously available. The extent of heterogeneity is extremely similar in all of these organisms, as judged by number, range of isoelectric points, and distribution of the isotubulins. A minimum of 6 alpha and 12 beta tubulins was resolved from all sources. Even the pattern of spots on two-dimensional peptide maps is remarkably similar. These similarities suggest that the populations of tubulin in all of these brains should have similar overall physical properties. It is particularly interesting that chicken, which has only four or five beta-tubulin genes, contains approximately 12 beta tubulins. Thus, post-translational modification must generate at least some of the tubulin heterogeneity. Mammalian species, which contain 15-20 tubulin DNA sequences, do not show any more tubulin protein heterogeneity than does chicken. This suggests that expression of only a small number of the mammalian genes may be required to generate the observed tubulin heterogeneity. Images PMID:6588378

  8. The trafficking protein Tmed2/p24beta(1) is required for morphogenesis of the mouse embryo and placenta.

    PubMed

    Jerome-Majewska, Loydie A; Achkar, Tala; Luo, Li; Lupu, Floria; Lacy, Elizabeth

    2010-05-01

    During vesicular transport between the endoplasmic reticulum and the Golgi, members of the TMED/p24 protein family form hetero-oligomeric complexes that facilitate protein-cargo recognition as well as vesicle budding. In addition, they regulate each other's level of expression. Despite analyses of TMED/p24 protein distribution in mammalian cells, yeast, and C. elegans, little is known about the role of this family in vertebrate embryogenesis. We report the presence of a single point mutation in Tmed2/p24beta(1) in a mutant mouse line, 99J, identified in an ENU mutagenesis screen for recessive developmental abnormalities. This mutation does not affect Tmed2/p24beta(1) mRNA levels but results in loss of TMED2/p24beta(1) protein. Prior to death at mid-gestation, 99J homozygous mutant embryos exhibit developmental delay, abnormal rostral-caudal elongation, randomized heart looping, and absence of the labyrinth layer of the placenta. We find that Tmed2/p24beta(1) is normally expressed in tissues showing morphological defects in 99J mutant embryos and that these affected tissues lack the TMED2/p24beta(1) oligomerization partners, TMED7/p24gamma(3) and TMED10/p24delta(1). Our data reveal a requirement for TMED2/p24beta(1) protein in the morphogenesis of the mouse embryo and placenta.

  9. Mechanical basis of morphogenesis and convergent evolution of spiny seashells.

    PubMed

    Chirat, Régis; Moulton, Derek E; Goriely, Alain

    2013-04-09

    Convergent evolution is a phenomenon whereby similar traits evolved independently in not closely related species, and is often interpreted in functional terms. Spines in mollusk seashells are classically interpreted as having repeatedly evolved as a defense in response to shell-crushing predators. Here we consider the morphogenetic process that shapes these structures and underlies their repeated emergence. We develop a mathematical model for spine morphogenesis based on the mechanical interaction between the secreting mantle edge and the calcified shell edge to which the mantle adheres during shell growth. It is demonstrated that a large diversity of spine structures can be accounted for through small variations in control parameters of this natural mechanical process. This physical mechanism suggests that convergent evolution of spines can be understood through a generic morphogenetic process, and provides unique perspectives in understanding the phenotypic evolution of this second largest phylum in the animal kingdom.

  10. Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling

    PubMed Central

    Sennett, Rachel; Rendl, Michael

    2012-01-01

    Embryonic hair follicle induction and formation are regulated by mesenchymal-epithelial interactions between specialized dermal cells and epidermal stem cells that switch to a hair fate. Similarly, during postnatal hair growth, communication between mesenchymal dermal papilla cells and surrounding epithelial matrix cells coordinates hair shaft production. Adult hair follicle regeneration in the hair cycle again is thought to be controlled by activating signals originating from the mesenchymal compartment and acting on hair follicle stem cells. Although many signaling pathways are implicated in hair follicle formation and growth, the precise nature, timing, and intersection of these inductive and regulatory signals remains elusive. The goal of this review is to summarize our current understanding and to discuss recent new insights into mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling. PMID:22960356

  11. Tomato Spotted Wilt Virus Particle Morphogenesis in Plant Cells

    PubMed Central

    Kikkert, Marjolein; Van Lent, Jan; Storms, Marc; Bodegom, Pentcho; Kormelink, Richard; Goldbach, Rob

    1999-01-01

    A model for the maturation of tomato spotted wilt virus (TSWV) particles is proposed, mainly based on results with a protoplast infection system, in which the chronology of different maturation events could be determined. By using specific monoclonal and polyclonal antisera in immunofluorescence and electron microscopy, the site of TSWV particle morphogenesis was determined to be the Golgi system. The viral glycoproteins G1 and G2 accumulate in the Golgi prior to a process of wrapping, by which the viral nucleocapsids obtain a double membrane. In a later stage of the maturation, these doubly enveloped particles fuse to each other and to the endoplasmic reticulum to form singly enveloped particles clustered in membranes. Similarities and differences between the maturation of animal-infecting (bunya)viruses and plant-infecting tospoviruses are discussed. PMID:9971812

  12. Neural tube morphogenesis in synthetic 3D microenvironments

    PubMed Central

    Ranga, Adrian; Girgin, Mehmet; Meinhardt, Andrea; Eberle, Dominic; Caiazzo, Massimiliano; Tanaka, Elly M.; Lutolf, Matthias P.

    2016-01-01

    Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemical and biophysical extracellular matrix (ECM) factors in promoting multicellular growth and reorganization. Here, we show how defined synthetic matrices can be used to explore the role of the ECM in the development of complex 3D neuroepithelial cysts that recapitulate key steps in early neurogenesis. We demonstrate how key ECM parameters are involved in specifying cytoskeleton-mediated symmetry-breaking events that ultimately lead to neural tube-like patterning along the dorsal–ventral (DV) axis. Such synthetic materials serve as valuable tools for studying the discrete action of extrinsic factors in organogenesis, and allow for the discovery of relationships between cytoskeletal mechanobiology and morphogenesis. PMID:27742791

  13. Brassinosteroid Levels Increase Drastically Prior to Morphogenesis of Tracheary Elements

    PubMed Central

    Yamamoto, Ryo; Fujioka, Shozo; Demura, Taku; Takatsuto, Suguru; Yoshida, Shigeo; Fukuda, Hiroo

    2001-01-01

    As the first step toward understanding the involvement of endogenous brassinosteroids (BRs) in cytodifferentiation, we analyzed biosynthetic activities of BRs in zinnia (Zinnia elegans L. cv Canary Bird) cells differentiating into tracheary elements. The results of feeding experiments suggested that both the early and late C6-oxidation pathways occur during tracheary element differentiation. Gas chromatography-mass spectrometry analysis revealed that five BRs, castasterone, typhasterol, 6-deoxocastasterone, 6-deoxotyphasterol, and 6-deoxoteasterone, actually existed in cultured zinnia cells and culture medium. Quantification of endogenous BRs in each stage of tracheary element differentiation by gas chromatography-mass spectrometry exhibited that they increased dramatically prior to the morphogenesis, which was consistent with the idea that BRs are necessary for the initiation of the final stage of tracheary element differentiation. Moreover, the proportion of each BR in culture medium was quite different from that in cells, suggesting that specific BRs are selectively secreted into medium and may function outside the cells. PMID:11161013

  14. Brassinosteroid levels increase drastically prior to morphogenesis of tracheary elements.

    PubMed

    Yamamoto, R; Fujioka, S; Demura, T; Takatsuto, S; Yoshida, S; Fukuda, H

    2001-02-01

    As the first step toward understanding the involvement of endogenous brassinosteroids (BRs) in cytodifferentiation, we analyzed biosynthetic activities of BRs in zinnia (Zinnia elegans L. cv Canary Bird) cells differentiating into tracheary elements. The results of feeding experiments suggested that both the early and late C6-oxidation pathways occur during tracheary element differentiation. Gas chromatography-mass spectrometry analysis revealed that five BRs, castasterone, typhasterol, 6-deoxocastasterone, 6-deoxotyphasterol, and 6-deoxoteasterone, actually existed in cultured zinnia cells and culture medium. Quantification of endogenous BRs in each stage of tracheary element differentiation by gas chromatography-mass spectrometry exhibited that they increased dramatically prior to the morphogenesis, which was consistent with the idea that BRs are necessary for the initiation of the final stage of tracheary element differentiation. Moreover, the proportion of each BR in culture medium was quite different from that in cells, suggesting that specific BRs are selectively secreted into medium and may function outside the cells.

  15. The green seaweed Ulva: a model system to study morphogenesis.

    PubMed

    Wichard, Thomas; Charrier, Bénédicte; Mineur, Frédéric; Bothwell, John H; Clerck, Olivier De; Coates, Juliet C

    2015-01-01

    Green macroalgae, mostly represented by the Ulvophyceae, the main multicellular branch of the Chlorophyceae, constitute important primary producers of marine and brackish coastal ecosystems. Ulva or sea lettuce species are some of the most abundant representatives, being ubiquitous in coastal benthic communities around the world. Nonetheless the genus also remains largely understudied. This review highlights Ulva as an exciting novel model organism for studies of algal growth, development and morphogenesis as well as mutualistic interactions. The key reasons that Ulva is potentially such a good model system are: (i) patterns of Ulva development can drive ecologically important events, such as the increasing number of green tides observed worldwide as a result of eutrophication of coastal waters, (ii) Ulva growth is symbiotic, with proper development requiring close association with bacterial epiphytes, (iii) Ulva is extremely developmentally plastic, which can shed light on the transition from simple to complex multicellularity and (iv) Ulva will provide additional information about the evolution of the green lineage.

  16. [The morphogenesis of mammalian cutaneous glands in evolutionary perspective].

    PubMed

    Chernova, O F

    2012-01-01

    The morphogenesis of mammalian cutaneous glands is considered based on the analysis of the literature and our own original data with the focus on the issues of gland polymorphism and specific features in postnatal development (from the case study of circumanal hepatoid glands of newborn domestic dogs), including the features reflecting the evolutionary relationships of various types of cutaneous glands. The hepatoid glands are a component of the glandular complex ofthe hair follicle, which also includes sebaceous and sweat glands; have a specific structure; and produce protein secretion by a merocrine pathway. Characteristic of these glands are wide polymorphism, sex- and age-related differences in the degree of development, occurrence in only a few phylogenetically related mammalian taxa (even-toed ungulates and carnivores); and a signaling type of their secretion. The data support the "generative concept," relying on the idea of a separate and independent origination of diverse derivatives of the external integuments.

  17. The morphogenesis of the vasculature in bovine fetal skin.

    PubMed Central

    El-Bab, M R; Schwarz, R; Godynicki, S

    1983-01-01

    The morphogenesis of the blood vessels in the bovine fetal skin, from the third to the tenth month of pregnancy was studied. Bovine fetal skin was found to be divided into 'unit vascular zones'. Each unit was centrally supplied with a ramus arteriosus cutaneous. The venous blood was drained from each unit through the tributaries of the plexus venosus dermis profundus. The formation of the venous plexus started at the fourth month and the primary elements of the arterial rete developed at the sixth month of intra-uterine life. Images Fig. 1 Fig. 2 Fig. 3 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:6885618

  18. Morphogenesis and bioluminescence in germination of red bean

    NASA Astrophysics Data System (ADS)

    Kai, Shoichi; Mitani, Tomohiko; Fujikawa, Masahiro

    1994-10-01

    Spontaneous bioluminescence and morphogenesis were investigated for the germination and the growth processes of a red bean seed under suppression of photosynthesis. Three types of shape in seed growth were observed in well controlled conditions: (1) no root hair and leaves, (2) with root hairs and leaves and (3) no root growth. In this article, growth dynamics for the first case was investigated. The average growth dynamics of the root length of a red bean after germination and its variance were well described by a simple logistic equation with a noise term. It was observed that the scaling property for the growth dynamics has held. Strong luminescence was observed at two inflection points of the logistic curve of the root growth. By the use of a two dimensional photon counting method, it was clarified that the strong emission was mainly radiated from the cell division zone near a root cap and rather less emission from an elongation area.

  19. Theoretical model for morphogenesis and cell sorting in Dictyostelium discoideum

    NASA Astrophysics Data System (ADS)

    Umeda, T.; Inouye, K.

    1999-02-01

    The morphogenetic movement and cell sorting in cell aggregates from the mound stage to the migrating slug stage of the cellular slime mold Dictyostelium discoideum were studied using a mathematical model. The model postulates that the motive force generated by the cells is in equilibrium with the internal pressure and mechanical resistance. The moving boundary problem derived from the force balance equation and the continuity equation has stationary solutions in which the aggregate takes the shape of a spheroid (or an ellipse in two-dimensional space) with the pacemaker at one of its foci, moving at a constant speed. Numerical calculations in two-dimensional space showed that an irregularly shaped aggregate changes its shape to become an ellipse as it moves. Cell aggregates consisting of two cell types differing in motive force exhibit cell sorting and become elongated, suggesting the importance of prestalk/prespore differentiation in the morphogenesis of Dictyostelium.

  20. Vertex models: from cell mechanics to tissue morphogenesis.

    PubMed

    Alt, Silvanus; Ganguly, Poulami; Salbreux, Guillaume

    2017-05-19

    Tissue morphogenesis requires the collective, coordinated motion and deformation of a large number of cells. Vertex model simulations for tissue mechanics have been developed to bridge the scales between force generation at the cellular level and tissue deformation and flows. We review here various formulations of vertex models that have been proposed for describing tissues in two and three dimensions. We discuss a generic formulation using a virtual work differential, and we review applications of vertex models to biological morphogenetic processes. We also highlight recent efforts to obtain continuum theories of tissue mechanics, which are effective, coarse-grained descriptions of vertex models.This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.

  1. Testing Turing’s theory of morphogenesis in chemical cells

    PubMed Central

    Tompkins, Nathan; Li, Ning; Girabawe, Camille; Heymann, Michael; Ermentrout, G. Bard; Epstein, Irving R.; Fraden, Seth

    2014-01-01

    Alan Turing, in “The Chemical Basis of Morphogenesis” [Turing AM (1952) Philos Trans R Soc Lond 237(641):37–72], described how, in circular arrays of identical biological cells, diffusion can interact with chemical reactions to generate up to six periodic spatiotemporal chemical structures. Turing proposed that one of these structures, a stationary pattern with a chemically determined wavelength, is responsible for differentiation. We quantitatively test Turing’s ideas in a cellular chemical system consisting of an emulsion of aqueous droplets containing the Belousov–Zhabotinsky oscillatory chemical reactants, dispersed in oil, and demonstrate that reaction-diffusion processes lead to chemical differentiation, which drives physical morphogenesis in chemical cells. We observe five of the six structures predicted by Turing. In 2D hexagonal arrays, a seventh structure emerges, incompatible with Turing’s original model, which we explain by modifying the theory to include heterogeneity. PMID:24616508

  2. Vertex models: from cell mechanics to tissue morphogenesis

    PubMed Central

    Alt, Silvanus; Ganguly, Poulami

    2017-01-01

    Tissue morphogenesis requires the collective, coordinated motion and deformation of a large number of cells. Vertex model simulations for tissue mechanics have been developed to bridge the scales between force generation at the cellular level and tissue deformation and flows. We review here various formulations of vertex models that have been proposed for describing tissues in two and three dimensions. We discuss a generic formulation using a virtual work differential, and we review applications of vertex models to biological morphogenetic processes. We also highlight recent efforts to obtain continuum theories of tissue mechanics, which are effective, coarse-grained descriptions of vertex models. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’. PMID:28348254

  3. 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

  4. Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.

    PubMed

    Boucherat, Olivier; Landry-Truchon, Kim; Bérubé-Simard, Félix-Antoine; Houde, Nicolas; Beuret, Laurent; Lezmi, Guillaume; Foulkes, William D; Delacourt, Christophe; Charron, Jean; Jeannotte, Lucie

    2015-09-01

    Yin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation whereas Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching and caused airway dilation similar to that seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be partly explained by the reduced expression of Shh, a transcriptional target of YY1, in lung endoderm, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the crucial requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.

  5. Atlastin GTPases are required for Golgi apparatus and ER morphogenesis.

    PubMed

    Rismanchi, Neggy; Soderblom, Cynthia; Stadler, Julia; Zhu, Peng-Peng; Blackstone, Craig

    2008-06-01

    The hereditary spastic paraplegias (SPG1-33) comprise a cluster of inherited neurological disorders characterized principally by lower extremity spasticity and weakness due to a length-dependent, retrograde axonopathy of corticospinal motor neurons. Mutations in the gene encoding the large oligomeric GTPase atlastin-1 are responsible for SPG3A, a common autosomal dominant hereditary spastic paraplegia. Here we describe a family of human GTPases, atlastin-2 and -3 that are closely related to atlastin-1. Interestingly, while atlastin-1 is predominantly localized to vesicular tubular complexes and cis-Golgi cisternae, mostly in brain, atlastin-2 and -3 are localized to the endoplasmic reticulum (ER) and are most enriched in other tissues. Knockdown of atlastin-2 and -3 levels in HeLa cells using siRNA (small interfering RNA) causes disruption of Golgi morphology, and these Golgi structures remain sensitive to brefeldin A treatment. Interestingly, expression of SPG3A mutant or dominant-negative atlastin proteins lacking GTPase activity causes prominent inhibition of ER reticularization, suggesting a role for atlastin GTPases in the formation of three-way junctions in the ER. However, secretory pathway trafficking as assessed using vesicular stomatitis virus G protein fused to green fluorescent protein (VSVG-GFP) as a reporter was essentially normal in both knockdown and dominant-negative overexpression conditions for all atlastins. Thus, the atlastin family of GTPases functions prominently in both ER and Golgi morphogenesis, but they do not appear to be required generally for anterograde ER-to-Golgi trafficking. Abnormal morphogenesis of the ER and Golgi resulting from mutations in atlastin-1 may ultimately underlie SPG3A by interfering with proper membrane distribution or polarity of the long corticospinal motor neurons.

  6. Turing mechanism underlying a branching model for lung morphogenesis

    PubMed Central

    Sun, Mingzhu

    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. PMID:28376090

  7. Collective cell migration drives morphogenesis of the kidney nephron.

    PubMed

    Vasilyev, Aleksandr; Liu, Yan; Mudumana, Sudha; Mangos, Steve; Lam, Pui-Ying; Majumdar, Arindam; Zhao, Jinhua; Poon, Kar-Lai; Kondrychyn, Igor; Korzh, Vladimir; Drummond, Iain A

    2009-01-06

    Tissue organization in epithelial organs is achieved during development by the combined processes of cell differentiation and morphogenetic cell movements. In the kidney, the nephron is the functional organ unit. Each nephron is an epithelial tubule that is subdivided into discrete segments with specific transport functions. Little is known about how nephron segments are defined or how segments acquire their distinctive morphology and cell shape. Using live, in vivo cell imaging of the forming zebrafish pronephric nephron, we found that the migration of fully differentiated epithelial cells accounts for both the final position of nephron segment boundaries and the characteristic convolution of the proximal tubule. Pronephric cells maintain adherens junctions and polarized apical brush border membranes while they migrate collectively. Individual tubule cells exhibit basal membrane protrusions in the direction of movement and appear to establish transient, phosphorylated Focal Adhesion Kinase-positive adhesions to the basement membrane. Cell migration continued in the presence of camptothecin, indicating that cell division does not drive migration. Lengthening of the nephron was, however, accompanied by an increase in tubule cell number, specifically in the most distal, ret1-positive nephron segment. The initiation of cell migration coincided with the onset of fluid flow in the pronephros. Complete blockade of pronephric fluid flow prevented cell migration and proximal nephron convolution. Selective blockade of proximal, filtration-driven fluid flow shifted the position of tubule convolution distally and revealed a role for cilia-driven fluid flow in persistent migration of distal nephron cells. We conclude that nephron morphogenesis is driven by fluid flow-dependent, collective epithelial cell migration within the confines of the tubule basement membrane. Our results establish intimate links between nephron function, fluid flow, and morphogenesis.

  8. Laser microbeam manipulation of cell morphogenesis growing in fungal hyphae

    NASA Astrophysics Data System (ADS)

    Bracker, Charles E.; Murphy, Douglas J.; Lopez-Franco, Rosamaria

    1997-05-01

    Laser microbeam irradiation at 820 nm predictably and reproducibly altered morphogenetic patterns in fungal cells. Optical tweezers were highly effective as localized, noninvasive, and largely nondestructive probes under precise spatial and temporal control. In growing hyphae, the position of the Spitzenkorper (a multicomponent complex containing mainly secretory vesicles in the hyphal apex), is correlated with the site of maximum cell expansion during tip growth. The Spitzenkorper was not trapped by the laser, but moved away from the trap, and could be `chased' around the cell by the laser beam. Consequently, the direction of cell elongation was readily changed by moving the Spitzenkorper. When the laser was held steady at the cytoplasmic surface immediately beside the Spitzenkorper, an adventitious branch hypha was initiated on the same side of the hypha, suggesting that unilateral disturbance of vesicle traffic initiated a new lateral Spitzenkorper and hyphal branch near the original hyphal apex. If moving vesicles were trapped by the laser beam and transported to a different area of the cytoplasm near the cell surface, the cell profile bulged where the vesicles were newly concentrated. Variations in the mode of vesicle transfer caused: (1) single and multiple bulges, (2) adventitious branch hyphae, (3) increased cell diameter, and (4) changing directions of hyphal elongation. Thus, laser tweezers emerge as a powerful tool for controlling patterns of cell morphogenesis. The findings strongly support the hypothesis that sites of vesicle concentration and release to the cell surface are important determinants of cell morphogenesis in fungi. This conclusion lends support to the basic premises of a modern mathematical model of hyphal tip growth (the hyphoid/VSC model) but does not in itself provide the information needed for a comprehensive and integrated explanation of the mechanism of cell growth in fungi.

  9. Breast cancer cell-derived matrix supports vascular morphogenesis.

    PubMed

    Hielscher, Abigail C; Qiu, Connie; Gerecht, Sharon

    2012-04-15

    The extracellular matrix (ECM), important for maintaining tissue homeostasis, is abnormally expressed in mammary tumors and additionally plays a crucial role in angiogenesis. We hypothesize that breast cancer cells (BCCs) deposit ECM that supports unique patterns of vascular morphogenesis of endothelial cells (ECs). Evaluation of ECM expression revealed that a nontumorigenic cell line (MCF10A), a tumorigenic cell line (MCF7), and a metastatic cell line (MDA-MB-231) express collagens I and IV, fibronectin, and laminin, with tenascin-C limited to MCF10A and MCF7. The amount of ECM deposited by BCCs was found to be higher in MCF10A compared with MCF7 and MDA231, with all ECM differing in their gross structure but similar in mean fiber diameter. Nonetheless, deposition of ECM from BCC lines was overall difficult to detect and insufficient to support capillary-like structure (CLS) formation of ECs. Therefore, a coculture approach was undertaken in which individual BCC lines were cocultured with fibroblasts. Variation in abundance of deposited ECM, deposition of ECM proteins, such as absent collagen I deposition from MDA231-fibroblast cocultures, and fibril organization was found. Deposited ECM from fibroblasts and each coculture supported rapid CLS formation of ECs. Evaluation of capillary properties revealed that CLS grown on ECM deposited from MDA231-fibroblast cocultures possessed significantly larger lumen diameters, occupied the greatest percentage of area, expressed the highest levels of von Willebrand factor, and expressed the greatest amount of E-selectin, which was upregulated independent of exposure to TNF-α. To our knowledge, this is the first study to report tumor cell ECM-mediated differences in vascular capillary features, and thus offers the framework for future investigations interrogating the role of the tumor ECM in supporting vascular morphogenesis.

  10. Update of vertebral cementoplasty in porotic patients

    PubMed Central

    Masala, Salvatore; Muto, Mario

    2015-01-01

    Vertebroplasty (VP) is a percutaneous mini-invasive technique developed in the late 1980s as antalgic and stabilizing treatment in patients affected by symptomatic vertebral fracture due to porotic disease, traumatic injury and primary or secondary vertebral spine tumors. The technique consists of a simple metameric injection of an inert cement (poly-methyl-methacrylate, PMMA), through a needle by trans-peduncular, parapeduncular or trans-somatic approach obtaining a vertebral augmentation and stabilization effect associated with pain relief. The technique is simple and fast, and should be performed under fluoroscopy or CT guidance in order to obtain a good result with low complication rate. The aim of this paper is to illustrate the utility of VP, the indications-contraindications criteria, how to technically perform the technique using imaging guidance, and the results and complications of this treatment in patients affected by symptomatic vertebral compression fracture. PMID:26015527

  11. 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.

  12. Cervicobrachialgia with congenital vertebral anomalies and diastematomyelia.

    PubMed

    Roosen, N; De Moor, J

    1984-05-01

    A case of diastematomyelia in an adult female patient is reported. The relationship of the cervicobrachialgia, which was the presenting sign, to the diastematomyelia and the congenital vertebral anomalies is discussed.

  13. A Case of Aerococcus Urinae Vertebral Osteomyelitis

    PubMed Central

    Jerome, Michael; Slim, Jihad; Sison, Raymund; Marton, Randy

    2015-01-01

    Aerococcus urinae is an aerobic, alpha hemolytic gram positive coccus bacterium that grows in pairs or clusters. We report the first case of vertebral osteomyelitis due to A. urinae. This has not been previously reported in the literature. PMID:26069429

  14. [Vertebral osteomyelitis associated with epidural block].

    PubMed

    Carrillo Esper, R; Cruz-Bautista, I

    2001-01-01

    Infectious complications after epidural anesthesia are infrequent and the most common are epidural and subdural abscess. We report one rare case of vertebral osteomyelitus associated with an epidural catheter and review the literature.

  15. [Osteocyte-network in various vertebrates].

    PubMed

    Yamaguchi, Akira

    2012-05-01

    Since aquatic and land vertebrates live in different habitats,the morphology and function of bone might be greatly affected by the habitats of each vertebrate. We histologically investigated the bones of various vertebrates including teleost fishes, amphibians, reptiles, and mammals. Teleost fishes exhibited either bones contained many osteocytes (cellular bone) or bones have few osteocytes (acellular bone) . The development of osteocyte lacunocanalicular system in the cellular bone of the fish is poor compared to those in amphibians, reptiles, and mammals. Bones in Xenopus laevis, a freshwater species, exhibited well-developed lacunocanalicular systems as well as those in reptiles and mammals. These studies indicates that the osteocyte lacunocanalicular system differs between teleost fishes and land vertebrates, but this is not directly related to aquatic habitat.

  16. Evolution of Herbivory in Terrestrial Vertebrates

    NASA Astrophysics Data System (ADS)

    Sues, Hans-Dieter

    2000-08-01

    Although herbivory probably first appeared over 300 million years ago, it only became established as a common feeding strategy during Late Permian times. Subsequently, herbivory evolved in numerous lineages of terrestrial vertebrates, and the acquisition of this mode of feeding was frequently associated with considerable evolutionary diversification in those lineages. This book represents a comprehensive overview of the evolution of herbivory in land-dwelling amniote tetrapods in recent years. In Evolution of Herbivory in Terrestrial Vertebrates, leading experts review the evolutionary history and structural adaptations required for feeding on plants in the major groups of land-dwelling vertebrates, especially dinosaurs and ungulate mammals. As such, this volume will be the definitive reference source on this topic for evolutionary biologists and vertebrate paleontologists.

  17. Sleep and orexins in nonmammalian vertebrates.

    PubMed

    Volkoff, Hélène

    2012-01-01

    Although a precise definition of "sleep" has yet to be established, sleep-like behaviors have been observed in all animals studied to date including mammals and nonmammalian vertebrates. Orexins are hypothalamic neuropeptides that are involved in the regulation of many physiological functions, including feeding, thermoregulation, cardiovascular control, as well as the control of the sleep-wakefulness cycle. To date, the knowledge on the functions of orexins in nonmammalian vertebrates is still limited, but the similarity of the structures of orexins and their receptors among vertebrates suggest that they have similar conserved physiological functions. This review describes our current knowledge on sleep in nonmammalian vertebrates (birds, reptiles, amphibians, and fish) and the possible role of orexins in the regulation of their energy homeostasis and arousal states.

  18. RFamide Peptides in Early Vertebrate Development

    PubMed Central

    Sandvik, Guro Katrine; Hodne, Kjetil; Haug, Trude Marie; Okubo, Kataaki; Weltzien, Finn-Arne

    2014-01-01

    RFamides (RFa) are neuropeptides involved in many different physiological processes in vertebrates, such as reproductive behavior, pubertal activation of the reproductive endocrine axis, control of feeding behavior, and pain modulation. As research has focused mostly on their role in adult vertebrates, the possible roles of these peptides during development are poorly understood. However, the few studies that exist show that RFa are expressed early in development in different vertebrate classes, perhaps mostly associated with the central nervous system. Interestingly, the related peptide family of FMRFa has been shown to be important for brain development in invertebrates. In a teleost, the Japanese medaka, knockdown of genes in the Kiss system indicates that Kiss ligands and receptors are vital for brain development, but few other functional studies exist. Here, we review the literature of RFa in early vertebrate development, including the possible functional roles these peptides may play. PMID:25538682

  19. Recombination Drives Vertebrate Genome Contraction

    PubMed Central

    Nam, Kiwoong; Ellegren, Hans

    2012-01-01

    Selective and/or neutral processes may govern variation in DNA content and, ultimately, genome size. The observation in several organisms of a negative correlation between recombination rate and intron size could be compatible with a neutral model in which recombination is mutagenic for length changes. We used whole-genome data on small insertions and deletions within transposable elements from chicken and zebra finch to demonstrate clear links between recombination rate and a number of attributes of reduced DNA content. Recombination rate was negatively correlated with the length of introns, transposable elements, and intergenic spacer and with the rate of short insertions. Importantly, it was positively correlated with gene density, the rate of short deletions, the deletion bias, and the net change in sequence length. All these observations point at a pattern of more condensed genome structure in regions of high recombination. Based on the observed rates of small insertions and deletions and assuming that these rates are representative for the whole genome, we estimate that the genome of the most recent common ancestor of birds and lizards has lost nearly 20% of its DNA content up until the present. Expansion of transposable elements can counteract the effect of deletions in an equilibrium mutation model; however, since the activity of transposable elements has been low in the avian lineage, the deletion bias is likely to have had a significant effect on genome size evolution in dinosaurs and birds, contributing to the maintenance of a small genome. We also demonstrate that most of the observed correlations between recombination rate and genome contraction parameters are seen in the human genome, including for segregating indel polymorphisms. Our data are compatible with a neutral model in which recombination drives vertebrate genome size evolution and gives no direct support for a role of natural selection in this process. PMID:22570634

  20. What is the general action of ghrelin for vertebrates? - comparisons of ghrelin's effects across vertebrates.

    PubMed

    Kaiya, Hiroyuki; Kangawa, Kenji; Miyazato, Mikiya

    2013-01-15

    Ten years and more passed since ghrelin was discovered. Various physiological actions of ghrelin have been documented in both mammalian and nonmammalian vertebrates. Do these actions have any commonality? In this review, we focused on several effects of ghrelin, and compared the effect across vertebrates. We would like to discuss possible general function of ghrelin in vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Role of Transpedicular Percutaneous Vertebral Biopsy for Diagnosis of Pathology in Vertebral Compression Fractures

    PubMed Central

    Nadkarni, Sunil; Hardikar, Sharad Moreshwar; Hardikar, Madan Sharad

    2016-01-01

    Study Design Retrospective observational study. Purpose To identify the role of percutaneous vertebral biopsy in histopathological diagnosis of vertebral compression fractures and to identify the frequency of unexpected malignancy in vertebral compression fractures. Overview of Literature Vertebral compression fractures are common in the Indian population. Magnetic resonance imaging and nuclear imaging have some limitations in the diagnosis of definitive pathology of vertebral compression fractures. Therefore, histological confirmation is necessary for definitive diagnosis and to plan appropriate management for patient. Methods A retrospective observational study was conducted involving 84 patients who underwent percutaneous vertebral biopsy between 2010 and 2014. We performed C-arm guided percutaneous transpedicular core vertebral biopsy of vertebral compression fractures under combination of local anesthesia and intravenous conscious sedation. Results Sufficient biopsy material was obtained in 79 of the 84 cases. In the other five cases, biopsy material was not sufficient for reporting. Out of the 79 cases, osteoporotic pathology was detected in 69 patients, malignancy was detected in 8 patients and no pathology was found in 2 patients. Two patients with distant metastases to vertebra were identified. Primary spinal malignancy was detected in 6 patients (1 unsuspected plasmacytoma, 5 diagnosed malignancy preoperatively). So, the frequency of unsuspected malignancy of this study was 1.19% (1/84). None of the patients had any complications. Conclusions C-arm guided percutaneous transpedicular vertebral biopsy is useful in obtaining definitive histopathological diagnosis of vertebral compression fractures, especially in differentiating malignant and non-malignant vertebral compression fractures and helping plan appropriate management of patients. The rate of unexpected malignancy in vertebral compression fracture was 1.19%. PMID:27790322

  2. Vertebrate Cells Express Protozoan Antigen after Hybridization

    NASA Astrophysics Data System (ADS)

    Crane, Mark St. J.; Dvorak, James A.

    1980-04-01

    Epimastigotes, the invertebrate host stage of Trypanosoma cruzi, the protozoan parasite causing Chagas' disease in man, were fused with vertebrate cells by using polyethylene glycol. Hybrid cells were selected on the basis of T. cruzi DNA complementation of biochemical deficiencies in the vertebrate cells. Some clones of the hybrid cells expressed T. cruzi-specific antigen. It might be possible to use selected antigens obtained from the hybrids as vaccines for immunodiagnosis or for elucidation of the pathogenesis of Chagas' disease.

  3. Diagnosis and treatment of vertebral compression fractures.

    PubMed

    Dewar, Cherie

    2015-01-01

    A healthy spine is an integral part of an individual's overall well-being. The spinal column's essential role in physiological and neurological function can be compromised when disease or trauma causes a vertebra to compress under the body's weight, producing a vertebral compression fracture. This is a common ailment among adults older than 65 years of age, especially for those with low bone mass or osteoporosis. This article describes vertebral compression fractures, with a special emphasis on medical imaging.

  4. Percutaneous Vertebral Body Augmentation: An Updated Review

    PubMed Central

    Omidi-Kashani, Farzad

    2014-01-01

    There are many medical conditions like osteoporosis, tumor, or osteonecrosis that weaken the structural strength of the vertebral body and prone it to fracture. Percutaneous vertebral augmentation that is usually applied by polymethylmethacrylate is a relatively safe, effective, and long lasting procedure commonly performed in these situations. In this paper, we updated a review of biomechanics, indications, contraindications, surgical techniques, complications, and overall prognosis of these minimally invasive spinal procedures. PMID:25379561

  5. Cervical vertebral fusion with anterior meningocele

    PubMed Central

    Chavredakis, Emmanuel; Carter, David; Bhojak, Manesh; Jenkinson, Michael D; Clark, Simon R

    2015-01-01

    We present the first described case of cervical vertebral fusion associated with anterior meningocele and syringomyelia. A 45-year-old woman presented with minor trauma, and plain cervical spine radiographs highlighted a congenital deformity of the cervical vertebral bodies. She had a normal neurological examination; however, further imaging revealed a meningocele and syringomyelia. This case highlights the importance of thorough imaging investigation when presented with a congenital deformity in order to detect and prevent development of degenerative spinal cord pathologies. PMID:25923673

  6. Vertebral osteomyelitis: clinical features and diagnosis.

    PubMed

    Eren Gök, S; Kaptanoğlu, E; Celikbaş, A; Ergönül, O; Baykam, N; Eroğlu, M; Dokuzoğuz, B

    2014-10-01

    We aimed to describe clinical and diagnostic features of vertebral osteomyelitis for differential diagnosis and treatment. This is a prospective observational study performed between 2002 and 2012 in Ankara Numune Education and Research Hospital in Ankara, Turkey. All the patients with vertebral osteomyelitis were followed for from 6 months to 3 years. In total, 214 patients were included in the study, 113 out of 214 (53%) were female. Out of 214 patients, 96 (45%) had brucellar vertebral osteomyelitis (BVO), 63 (29%) had tuberculous vertebral osteomyelitis (TVO), and 55 (26%) had pyogenic vertebral osteomyelitis (PVO). Mean number of days between onset of symptoms and establishment of diagnosis was greater with the patients with TVO (266 days) than BVO (115 days) or PVO (151 days, p <0.001). In blood cultures, Brucella spp. were isolated from 35 of 96 BVO patients (35%). Among 55 PVO patients, the aetiological agent was isolated in 11 (20%) patients. For tuberculin skin test >15 mm, sensitivity was 0.66, specificity was 0.97, positive predictive value was 0.89, negative predictive value was 0.88, and receiver operating characteristics area was 0.8. Tuberculous and brucellar vertebral osteomyelitis remained the leading causes of vertebral osteomyelitis with delayed diagnosis. In differential diagnosis of vertebral osteomyelitis, consumption of unpasteurized cheese, dealing with husbandry, sweating, arthralgia, hepatomegaly, elevated alanine transaminase, and lumbar involvement in magnetic resonance imaging were found to be predictors of BVO, thoracic involvement in magnetic resonance imaging and tuberculin skin test > 15 mm were found to be predictors of TVO, and history of spinal surgery and leucocytosis were found to be predictors of PVO.

  7. Concomitant and previous osteoporotic vertebral fractures

    PubMed Central

    Lenski, Markus; Büser, Natalie; Scherer, Michael

    2017-01-01

    Background and purpose Patients with osteoporosis who present with an acute onset of back pain often have multiple fractures on plain radiographs. Differentiation of an acute osteoporotic vertebral fracture (AOVF) from previous fractures is difficult. The aim of this study was to investigate the incidence of concomitant AOVFs and previous OVFs in patients with symptomatic AOVFs, and to identify risk factors for concomitant AOVFs. Patients and methods This was a prospective epidemiological study based on the Registry of Pathological Osteoporotic Vertebral Fractures (REPAPORA) with 1,005 patients and 2,874 osteoporotic vertebral fractures, which has been running since February 1, 2006. Concomitant fractures are defined as at least 2 acute short-tau inversion recovery (STIR-) positive vertebral fractures that happen concomitantly. A previous fracture is a STIR-negative fracture at the time of initial diagnostics. Logistic regression was used to examine the influence of various variables on the incidence of concomitant fractures. Results More than 99% of osteoporotic vertebral fractures occurred in the thoracic and lumbar spine. The incidence of concomitant fractures at the time of first patient contact was 26% and that of previous fractures was 60%. The odds ratio (OR) for concomitant fractures decreased with a higher number of previous fractures (OR =0.86; p = 0.03) and higher dual-energy X-ray absorptiometry T-score (OR =0.72; p = 0.003). Interpretation Concomitant and previous osteoporotic vertebral fractures are common. Risk factors for concomitant fractures are a low T-score and a low number of previous vertebral fractures in cases of osteoporotic vertebral fracture. An MRI scan of the the complete thoracic and lumbar spine with STIR sequence reduces the risk of under-diagnosis and under-treatment. PMID:28056595

  8. Radiotherapy in the treatment of vertebral hemangiomas

    SciTech Connect

    Faria, S.L.; Schlupp, W.R.; Chiminazzo, H. Jr.

    1985-02-01

    Symptomatic vertebral hemangiomas are not common. Although radiotherapy has been used as treatment, the data are sparse concerning total dose, fractionation and results. The authors report nine patients with vertebral hemangioma treated with 3000-4000 rad, 200 rad/day, 5 fractions per week, followed from 6 to 62 months. Seventy-seven percent had complete or almost complete disappearance of the symptoms. Radiotherapy schedules are discussed.

  9. The origins of colour vision in vertebrates.

    PubMed

    Collin, Shaun P; Trezise, Ann E O

    2004-07-01

    The capacity for colour vision is mediated by the comparison of the signal intensities from photoreceptors of two or more types that differ in spectral sensitivity. Morphological, physiological and molecular analyses of the retina in an agnathan (jawless) fish, the lamprey Geotria australis, may hold important clues to the origins of colour vision in vertebrates. Lampreys are extant representatives of an ancient group of vertebrates, the origins of which are thought to date back to at least the early Cambrian, approximately 540 million years ago. G. australis possesses five photoreceptor types, each with cone-like ultrastructural features and different spectral sensitivities. Recent molecular genetic studies have also revealed that five visual pigment (opsin) genes are expressed in the retina, each of which is orthologous to the major classes of vertebrate opsin genes. These findings reveal that multiple opsin genes originated very early in vertebrate evolution, prior to the separation of the jawed and jawless vertebrate lineages, thereby providing the genetic basis for colour vision in all vertebrates.

  10. Retroviral Diversity and Distribution in Vertebrates

    PubMed Central

    Herniou, Elisabeth; Martin, Joanne; Miller, Karen; Cook, James; Wilkinson, Mark; Tristem, Michael

    1998-01-01

    We used the PCR to screen for the presence of endogenous retroviruses within the genomes of 18 vertebrate orders across eight classes, concentrating on reptilian, amphibian, and piscine hosts. Thirty novel retroviral sequences were isolated and characterized by sequencing approximately 1 kb of their encoded protease and reverse transcriptase genes. Isolation of novel viruses from so many disparate hosts suggests that retroviruses are likely to be ubiquitous within all but the most basal vertebrate classes and, furthermore, gives a good indication of the overall retroviral diversity within vertebrates. Phylogenetic analysis demonstrated that viruses clustering with (but not necessarily closely related to) the spumaviruses and murine leukemia viruses are widespread and abundant in vertebrate genomes. In contrast, we were unable to identify any viruses from hosts outside of mammals and birds which grouped with the other five currently recognized retroviral genera: the lentiviruses, human T-cell leukemia-related viruses, avian leukemia virus-related retroviruses, type D retroviruses, and mammalian type B retroviruses. There was also some indication that viruses isolated from individual vertebrate classes tended to cluster together in phylogenetic reconstructions. This implies that the horizontal transmission of at least some retroviruses, between some vertebrate classes, occurs relatively infrequently. It is likely that many of the retroviral sequences described here are distinct enough from those of previously characterized viruses to represent novel retroviral genera. PMID:9621058

  11. 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

  12. Vertebral deformities identified by vertebral fracture assessment: associations with clinical characteristics and bone mineral density.

    PubMed

    Jacobs-Kosmin, Dana; Sandorfi, Nora; Murray, Heather; Abruzzo, John L

    2005-01-01

    Whether vertebral fractures identified on radiographs are painful or not, they are associated with increased morbidity and mortality. Vertebral fractures on X-rays correlate with low bone mineral density (BMD) at the spine and hip in addition to several clinical characteristics. Evidence suggests that vertebral deformities detected by X-ray and by vertebral fracture assessment (VFA) show good agreement. We examined the relationship between VFA-detected vertebral deformities and patient characteristics as well as BMD by analyzing the records of 432 patients who had undergone dual-energy X-ray absorptiometry (DXA) scans with VFA. Patients' demographic data and T-scores were obtained from patient questionnaires and DXA scans. We categorized vertebral deformities by type and severity. Patients with vertebral deformities were significantly older and more likely to report a history of fracture after childhood. Significantly more estrogen use was reported in patients without deformity. Those with deformities had significantly lower T-scores at the femoral neck and total hip but not at the spine. Increased severity and number of deformities correlated with lower T-scores at the total hip and femoral neck but not the spine. In conclusion, vertebral deformities detected by VFA, like those on X-ray, correlate with both clinical characteristics and reduced bone mass at the hip. These relationships, in addition to rapid performance, convenience, and minimal radiation exposure, indicate VFA-detected vertebral deformities are a valuable adjunct in identifying patients in need of additional evaluation and treatment.

  13. Oriented cell motility and division underlie early limb bud morphogenesis.

    PubMed

    Wyngaarden, Laurie A; Vogeli, Kevin M; Ciruna, Brian G; Wells, Mathew; Hadjantonakis, Anna-Katerina; Hopyan, Sevan

    2010-08-01

    The vertebrate limb bud arises from lateral plate mesoderm and its overlying ectoderm. Despite progress regarding the genetic requirements for limb development, morphogenetic mechanisms that generate early outgrowth remain relatively undefined. We show by live imaging and lineage tracing in different vertebrate models that the lateral plate contributes mesoderm to the early limb bud through directional cell movement. The direction of cell motion, longitudinal cell axes and bias in cell division planes lie largely parallel to one another along the rostrocaudal (head-tail) axis in lateral plate mesoderm. Transition of these parameters from a rostrocaudal to a mediolateral (outward from the body wall) orientation accompanies early limb bud outgrowth. Furthermore, we provide evidence that Wnt5a acts as a chemoattractant in the emerging limb bud where it contributes to the establishment of cell polarity that is likely to underlie the oriented cell behaviours.

  14. Crystal-surface-induced simultaneous synthesis and hierarchical morphogenesis of conductive polymers.

    PubMed

    Kuwabara, Kento; Oaki, Yuya; Muramatsu, Ryo; Imai, Hiroaki

    2015-06-14

    The surface of oxidant crystals facilitates the simultaneous synthesis and morphogenesis of conductive polymer materials. Oxidant crystals as a condensed phase of the oxidative agent induce the formation of the conductive polymer nanoparticles and their accumulated films.

  15. A critical role for NF2 and the Hippo pathway in branching morphogenesis.

    PubMed

    Reginensi, Antoine; Enderle, Leonie; Gregorieff, Alex; Johnson, Randy L; Wrana, Jeffrey L; McNeill, Helen

    2016-08-02

    Branching morphogenesis is a complex biological process common to the development of most epithelial organs. Here we demonstrate that NF2, LATS1/2 and YAP play a critical role in branching morphogenesis in the mouse kidney. Removal of Nf2 or Lats1/2 from the ureteric bud (UB) lineage causes loss of branching morphogenesis that is rescued by loss of one copy of Yap and Taz, and phenocopied by YAP overexpression. Mosaic analysis demonstrates that cells with high YAP expression have reduced contribution to UB tips, similar to Ret(-/-) cells, and that YAP suppresses RET signalling and tip identity. Conversely, Yap/Taz UB-deletion leads to cyst-like branching and expansion of UB tip markers, suggesting a shift towards tip cell identity. Based on these data we propose that NF2 and the Hippo pathway locally repress YAP/TAZ activity in the UB to promote subsequent splitting of the tip to allow branching morphogenesis.

  16. sall1 and sall4 repress pou5f3 family expression to allow neural patterning, differentiation, and morphogenesis in Xenopus laevis.

    PubMed

    Exner, Cameron R T; Kim, Albert Y; Mardjuki, Sarah M; Harland, Richard M

    2017-03-18

    The embryonic precursor of the vertebrate central nervous system, the neural plate, is patterned along the anterior-posterior axis and shaped by morphogenetic movements early in development. We previously identified the genes sall1 and sall4, known regulators of pluripotency in other contexts, as transcriptional targets of developmental signaling pathways that regulate neural development. Here, we demonstrate that these two genes are required for induction of posterior neural fates, the cell shape changes that contribute to neural tube closure, and later neurogenesis. Upon sall1 or sall4 knockdown, defects are associated with the failure of the neural plate to differentiate. Consistent with this, sall-deficient neural tissue exhibits an aberrant upregulation of pou5f3 family genes, the Xenopus homologs of the mammalian stem cell maintenance factor Pou5f1 (Oct4). Furthermore, overexpression of pou5f3 genes in Xenopus causes defects in neural patterning, morphogenesis, and differentiation that phenocopy those observed in sall1 and sall4 morphants. In all, this work shows that both sall1 and sall4 act to repress pou5f3 family gene expression in the neural plate, thereby allowing vertebrate neural development to proceed.

  17. A Systematic Screen for Tube Morphogenesis and Branching Genes in the Drosophila Tracheal System

    PubMed Central

    Ghabrial, Amin S.; Levi, Boaz P.; Krasnow, Mark A.

    2011-01-01

    Many signaling proteins and transcription factors that induce and pattern organs have been identified, but relatively few of the downstream effectors that execute morphogenesis programs. Because such morphogenesis genes may function in many organs and developmental processes, mutations in them are expected to be pleiotropic and hence ignored or discarded in most standard genetic screens. Here we describe a systematic screen designed to identify all Drosophila third chromosome genes (∼40% of the genome) that function in development of the tracheal system, a tubular respiratory organ that provides a paradigm for branching morphogenesis. To identify potentially pleiotropic morphogenesis genes, the screen included analysis of marked clones of homozygous mutant tracheal cells in heterozygous animals, plus a secondary screen to exclude mutations in general “house-keeping” genes. From a collection including more than 5,000 lethal mutations, we identified 133 mutations representing ∼70 or more genes that subdivide the tracheal terminal branching program into six genetically separable steps, a previously established cell specification step plus five major morphogenesis and maturation steps: branching, growth, tubulogenesis, gas-filling, and maintenance. Molecular identification of 14 of the 70 genes demonstrates that they include six previously known tracheal genes, each with a novel function revealed by clonal analysis, and two well-known growth suppressors that establish an integral role for cell growth control in branching morphogenesis. The rest are new tracheal genes that function in morphogenesis and maturation, many through cytoskeletal and secretory pathways. The results suggest systematic genetic screens that include clonal analysis can elucidate the full organogenesis program and that over 200 patterning and morphogenesis genes are required to build even a relatively simple organ such as the Drosophila tracheal system. PMID:21750678

  18. Adhesion-Linked Protein Tyrosine Phosphatases, Morphogenesis and Breast Cancer Progression

    DTIC Science & Technology

    2004-07-01

    Award Number: DAMD17-03-1-0496 TITLE: Adhesion-linked Protein Tyrosine Phosphatases, Morphogenesis and Breast Cancer Progression PRINCIPAL...Adhesion-linked Protein Tyrosine Phosphatases, DAMD17-03-1-0496 Morphogenesis and Breast Cancer Progression 6. AUTHOR(S) Valerie M. Weaver, Ph.D. 7...we identified the Band 4.1 PTPs MEG1 and D1 as two candidate PTP metastasis suppressors. Our studies show that during MEC differentiation PTP MEG1

  19. A mosaic genetic screen for genes necessary for Drosophila mushroom body neuronal morphogenesis.

    PubMed

    Reuter, John E; Nardine, Timothy M; Penton, Andrea; Billuart, Pierre; Scott, Ethan K; Usui, Tadao; Uemura, Tadashi; Luo, Liqun

    2003-03-01

    Neurons undergo extensive morphogenesis during development. To systematically identify genes important for different aspects of neuronal morphogenesis, we performed a genetic screen using the MARCM system in the mushroom body (MB) neurons of the Drosophila brain. Mutations on the right arm of chromosome 2 (which contains approximately 20% of the Drosophila genome) were made homozygous in a small subset of uniquely labeled MB neurons. Independently mutagenized chromosomes (4600) were screened, yielding defects in neuroblast proliferation, cell size, membrane trafficking, and axon and dendrite morphogenesis. We report mutations that affect these different aspects of morphogenesis and phenotypically characterize a subset. We found that roadblock, which encodes a dynein light chain, exhibits reduced cell number in neuroblast clones, reduced dendritic complexity and defective axonal transport. These phenotypes are nearly identical to mutations in dynein heavy chain Dhc64 and in Lis1, the Drosophila homolog of human lissencephaly 1, reinforcing the role of the dynein complex in cell proliferation, dendritic morphogenesis and axonal transport. Phenotypic analysis of short stop/kakapo, which encodes a large cytoskeletal linker protein, reveals a novel function in regulating microtubule polarity in neurons. MB neurons mutant for flamingo, which encodes a seven transmembrane cadherin, extend processes beyond their wild-type dendritic territories. Overexpression of Flamingo results in axon retraction. Our results suggest that most genes involved in neuronal morphogenesis play multiple roles in different aspects of neural development, rather than performing a dedicated function limited to a specific process.

  20. Lateral root morphogenesis is dependent on the mechanical properties of the overlaying tissues.

    PubMed

    Lucas, Mikaël; Kenobi, Kim; von Wangenheim, Daniel; Voβ, Ute; Swarup, Kamal; De Smet, Ive; Van Damme, Daniël; Lawrence, Tara; Péret, Benjamin; Moscardi, Eric; Barbeau, Daniel; Godin, Christophe; Salt, David; Guyomarc'h, Soazig; Stelzer, Ernst H K; Maizel, Alexis; Laplaze, Laurent; Bennett, Malcolm J

    2013-03-26

    In Arabidopsis, lateral root primordia (LRPs) originate from pericycle cells located deep within the parental root and have to emerge through endodermal, cortical, and epidermal tissues. These overlaying tissues place biomechanical constraints on the LRPs that are likely to impact their morphogenesis. This study probes the interplay between the patterns of cell division, organ shape, and overlaying tissues on LRP morphogenesis by exploiting recent advances in live plant cell imaging and image analysis. Our 3D/4D image analysis revealed that early stage LRPs exhibit tangential divisions that create a ring of cells corralling a population of rapidly dividing cells at its center. The patterns of division in the latter population of cells during LRP morphogenesis are not stereotypical. In contrast, statistical analysis demonstrated that the shape of new LRPs is highly conserved. We tested the relative importance of cell division pattern versus overlaying tissues on LRP morphogenesis using mutant and transgenic approaches. The double mutant aurora1 (aur1) aur2 disrupts the pattern of LRP cell divisions and impacts its growth dynamics, yet the new organ's dome shape remains normal. In contrast, manipulating the properties of overlaying tissues disrupted LRP morphogenesis. We conclude that the interaction with overlaying tissues, rather than the precise pattern of divisions, is most important for LRP morphogenesis and optimizes the process of lateral root emergence.

  1. Vertebral artery dissecting aneurysm treated by internal trapping via the contralateral vertebral artery: A case report

    PubMed Central

    2015-01-01

    A 42-year-old man with a history of sudden onset of severe headache followed by consciousness disturbance was brought to our hospital. Radiological examinations revealed subarachnoid hemorrhage, associated with rupture of a left vertebral artery dissecting aneurysm. Initially, internal trapping was attempted via the ipsilateral vertebral artery. However, the microcatheter could not be navigated through the true lumen to the distal side of the vertebral artery. Subsequently, therefore, the guiding catheter was placed in the right vertebral artery, and the microcatheter was retrogradely navigated successfully through the lesion to the proximal side of the left vertebral artery. Finally, the lesion was completely embolized with electrodetachable coils without complications. However, the patient died after the operation because of deterioration of the general condition. The postmortem examination revealed how an intimal flap had interfered with the antegrade navigation of the microcatheter in the lesion. The present case showed that endovascular treatment for a vertebral artery dissecting aneurysm via the contralateral vertebral artery may be a useful option in cases where antegrade navigation of the microcatheter via the ipsilateral vertebral artery is found to be difficult. PMID:26116649

  2. Vertebral artery dissecting aneurysm treated by internal trapping via the contralateral vertebral artery: A case report.

    PubMed

    Kojima, Atsuhiro

    2015-10-01

    A 42-year-old man with a history of sudden onset of severe headache followed by consciousness disturbance was brought to our hospital. Radiological examinations revealed subarachnoid hemorrhage, associated with rupture of a left vertebral artery dissecting aneurysm. Initially, internal trapping was attempted via the ipsilateral vertebral artery. However, the microcatheter could not be navigated through the true lumen to the distal side of the vertebral artery. Subsequently, therefore, the guiding catheter was placed in the right vertebral artery, and the microcatheter was retrogradely navigated successfully through the lesion to the proximal side of the left vertebral artery. Finally, the lesion was completely embolized with electrodetachable coils without complications. However, the patient died after the operation because of deterioration of the general condition. The postmortem examination revealed how an intimal flap had interfered with the antegrade navigation of the microcatheter in the lesion. The present case showed that endovascular treatment for a vertebral artery dissecting aneurysm via the contralateral vertebral artery may be a useful option in cases where antegrade navigation of the microcatheter via the ipsilateral vertebral artery is found to be difficult.

  3. Filling gaps about mimivirus entry, uncoating and morphogenesis.

    PubMed

    Andrade, Ana Cláudia Dos Santos Pereira; Rodrigues, Rodrigo Araújo Lima; Oliveira, Graziele Pereira; Andrade, Kétyllen Reis; Bonjardim, Cláudio Antônio; La Scola, Bernard; Kroon, Erna Geessien; Abrahão, Jônatas Santos

    2017-09-06

    Since the discovery of mimivirus, its unusual structural and genomic features have raised great interest in the study of its biology; however, many aspects concerning its replication cycle remain uncertain. In this study, extensive analyses of electron microscope images, as well as biological assays, shed light on unclear points concerning the mimivirus replication cycle. Here, we demonstrate that cytochalasin treatment, a phagocytosis inhibitor, impacts negatively on the incorporation of mimivirus particles by Acanthamoeba castellanii, causing a negative effect on viral growth in amoebae monolayers. The treatment of amoebas with bafilomicin impacts significantly on mimivirus uncoating and replication. In conjunction with microscopic analyses, these data suggest that mimiviruses indeed depend on phagocytosis for entry into amoebas, and particle uncoating (and stargate opening) appears to be dependent on phagosome acidification. In depth analyses of particle morphogenesis suggests that the mimivirus capsids are assembled from growing lamellar structures. Despite proposals of previous studies that genome acquisition occurs before the acquisition of fibrils, our results clearly demonstrate that the genome and fibrils can be acquired simultaneously. Our data suggest the existence of a specific area surrounding the core of the viral factory, where particles acquire the surface fibrils. Furthermore, we reinforce that defective particles can be formed even in the absence of virophages. Our work provides new information about unexplored steps in the life cycle of mimiviruses.IMPORTANCE Investigating the viral life cycle is essential to a better understanding of viruses' biology. The combination of biological assays and microscope images allows a clear view of the biological features of viruses. Since the discovery of mimivirus, many studies have been conducted to characterize its replication cycle, but many gaps remain to be filled. In this study, we conducted a new

  4. Morphogenesis of honeybee hypopharyngeal gland during pupal development.

    PubMed

    Klose, Sascha Peter; Rolke, Daniel; Baumann, Otto

    2017-01-01

    The hypopharyngeal gland of worker bees contributes to the production of the royal jelly fed to queens and larvae. The gland consists of thousands of two-cell units that are composed of a secretory cell and a duct cell and that are arranged in sets of about 12 around a long collecting duct. By fluorescent staining, we have examined the morphogenesis of the hypopharyngeal gland during pupal life, from a saccule lined by a pseudostratified epithelium to the elaborate organ of adult worker bees. The hypopharyngeal gland develops as follows. (1) Cell proliferation occurs during the first day of pupal life in the hypopharyngeal gland primordium. (2) Subsequently, the epithelium becomes organized into rosette-like units of three cells. Two of these will become the secretory cell and the duct cell of the adult secretory units; the third cell contributes only temporarily to the development of the secretory units and is eliminated by apoptosis in the second half of pupal life. (3) The three-cell units of flask-shaped cells undergo complex changes in cell morphology. Thus, by mid-pupal stage, the gland is structurally similar to the adult hypopharyngeal gland. (4) Concomitantly, the prospective secretory cell attains its characteristic subcellular organization by the invagination of a small patch of apical membrane domain, its extension to a tube of about 100 μm in length (termed a canaliculus), and the expansion of the tube to a diameter of about 3 μm. (6) Finally, the canaliculus-associated F-actin system becomes reorganized into rings of bundled actin filaments that are positioned at regular distances along the membrane tube. The morphogenesis of the secretory units in the hypopharyngeal gland of the worker bee seems to be based on a developmental program that is conserved, with slight modification, among insects for the production of dermal glands. Elaboration of the secretory cell as a unicellular seamless epithelial tube occurs by invagination of the apical

  5. Evolution of innate and adaptive immune systems in jawless vertebrates.

    PubMed

    Kasamatsu, Jun

    2013-01-01

    Because jawless vertebrates are the most primitive vertebrates, they have been studied to gain understanding of the evolutionary processes that gave rise to the innate and adaptive immune systems in vertebrates. Jawless vertebrates have developed lymphocyte-like cells that morphologically resemble the T and B cells of jawed vertebrates, but they express variable lymphocyte receptors (VLRs) instead of the T and B cell receptors that specifically recognize antigens in jawed vertebrates. These VLRs act as antigen receptors, diversity being generated in their antigen-binding sites by assembly of highly diverse leucine-rich repeat modules. Therefore, jawless vertebrates have developed adaptive immune systems based on the VLRs. Although pattern recognition receptors, including Toll-like receptors (TLRs) and Rig-like receptors (RLRs), and their adaptor genes are conserved in jawless vertebrates, some transcription factor and inflammatory cytokine genes in the TLR and RLR pathways are not present. However, like jawed vertebrates, the initiation of adaptive immune responses in jawless vertebrates appears to require prior activation of the innate immune system. These observations imply that the innate immune systems of jawless vertebrates have a unique molecular basis that is distinct from that of jawed vertebrates. Altogether, although the molecular details of the innate and adaptive immune systems differ between jawless and jawed vertebrates, jawless vertebrates have developed versions of these immune systems that are similar to those of jawed vertebrates. © 2012 The Societies and Wiley Publishing Asia Pty Ltd.

  6. Vertebral Column Resection for Rigid Spinal Deformity

    PubMed Central

    Laratta, Joseph L.; Petridis, Petros; Shillingford, Jamal N.; Lehman, Ronald A.; Lenke, Lawrence G.

    2017-01-01

    Study Design: Broad narrative review. Objective: To review the evolution, operative technique, outcomes, and complications associated with posterior vertebral column resection. Methods: A literature review of posterior vertebral column resection was performed. The authors’ surgical technique is outlined in detail. The authors’ experience and the literature regarding vertebral column resection are discussed at length. Results: Treatment of severe, rigid coronal and/or sagittal malalignment with posterior vertebral column resection results in approximately 50–70% correction depending on the type of deformity. Surgical site infection rates range from 2.9% to 9.7%. Transient and permanent neurologic injury rates range from 0% to 13.8% and 0% to 6.3%, respectively. Although there are significant variations in EBL throughout the literature, it can be minimized by utilizing tranexamic acid intraoperatively. Conclusion: The ability to correct a rigid deformity in the spine relies on osteotomies. Each osteotomy is associated with a particular magnitude of correction at a single level. Posterior vertebral column resection is the most powerful posterior osteotomy method providing a successful correction of fixed complex deformities. Despite meticulous surgical technique and precision, this robust osteotomy technique can be associated with significant morbidity even in the most experienced hands. PMID:28660112

  7. Vertebrate extracellular preovulatory and postovulatory egg coats.

    PubMed

    Menkhorst, Ellen; Selwood, Lynne

    2008-11-01

    Extracellular egg coats deposited by maternal or embryonic tissues surround all vertebrate conceptuses during early development. In oviparous species, the time of hatching from extracellular coats can be considered equivalent to the time of birth in viviparous species. Extracellular coats must be lost during gestation for implantation and placentation to occur in some viviparous species. In the most recent classification of vertebrate extracellular coats, Boyd and Hamilton (Cleavage, early development and implantation of the egg. In: Parkes AS (ed.), Marshall's Physiology of Reproduction, vol. 2, 3rd ed. London: Longmans, Green & Co; 1961:1-126) defined the coat synthesized by the oocyte during oogenesis as primary and the coat deposited by follicle cells surrounding the oocyte as secondary. Tertiary egg coats are those synthesized and deposited around the primary or secondary coat by the maternal reproductive tract. This classification is difficult to reconcile with recent data collected using modern molecular biological techniques that can accurately establish the site of coat precursor synthesis and secretion. We propose that a modification to the classification by Boyd and Hamilton is required. Vertebrate egg coats should be classed as belonging to the following two broad groups: the preovulatory coat, which is deposited during oogenesis by the oocyte or follicle cells, and the postovulatory coats, which are deposited after fertilization by the reproductive tract or conceptus. This review discusses the origin and classification of vertebrate extracellular preovulatory and postovulatory coats and illustrates what is known about coat homology between the vertebrate groups.

  8. Vertebral Column Resection for Rigid Spinal Deformity.

    PubMed

    Saifi, Comron; Laratta, Joseph L; Petridis, Petros; Shillingford, Jamal N; Lehman, Ronald A; Lenke, Lawrence G

    2017-05-01

    Broad narrative review. To review the evolution, operative technique, outcomes, and complications associated with posterior vertebral column resection. A literature review of posterior vertebral column resection was performed. The authors' surgical technique is outlined in detail. The authors' experience and the literature regarding vertebral column resection are discussed at length. Treatment of severe, rigid coronal and/or sagittal malalignment with posterior vertebral column resection results in approximately 50-70% correction depending on the type of deformity. Surgical site infection rates range from 2.9% to 9.7%. Transient and permanent neurologic injury rates range from 0% to 13.8% and 0% to 6.3%, respectively. Although there are significant variations in EBL throughout the literature, it can be minimized by utilizing tranexamic acid intraoperatively. The ability to correct a rigid deformity in the spine relies on osteotomies. Each osteotomy is associated with a particular magnitude of correction at a single level. Posterior vertebral column resection is the most powerful posterior osteotomy method providing a successful correction of fixed complex deformities. Despite meticulous surgical technique and precision, this robust osteotomy technique can be associated with significant morbidity even in the most experienced hands.

  9. AmphiFoxE4, an amphioxus winged helix/forkhead gene encoding a protein closely related to vertebrat