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Andrew J Copp - One of the best experts on this subject based on the ideXlab platform.
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dynamic acetylation profile during mammalian Neurulation
Birth defects research, 2020Co-Authors: Valentina Massa, Dawn Savery, Laura Avagliano, Paolo Grazioli, Sandra C P De Castro, Chiara Parodi, Patrizia Vergani, Serena Cuttin, Gaetano Bulfamante, Andrew J CoppAbstract:BACKGROUND: Neural tube defects (NTDs) result from failure of neural tube closure during embryogenesis. These severe birth defects of the central nervous system include anencephaly and spina bifida, and affect 0.5-2 per 1,000 pregnancies worldwide in humans. It has been demonstrated that acetylation plays a pivotal role during neural tube closure, as animal models for defective histone acetyltransferase proteins display NTDs. Acetylation represents an important component of the complex network of posttranslational regulatory interactions, suggesting a possible fundamental role during primary Neurulation events. This study aimed to assess protein acetylation contribution to early patterning of the central nervous system both in human and murine specimens. METHODS: We used both human and mouse (Cited2 (-/-) ) samples to analyze the dynamic acetylation of proteins during embryo development through immunohistochemistry, western blot analysis and quantitative polymerase chain reaction. RESULTS: We report the dynamic profile of histone and protein acetylation status during neural tube closure. We also report a rescue effect in an animal model by chemical p53 inhibition. CONCLUSIONS: Our data suggest that the p53-acetylation equilibrium may play a role in primary Neurulation in mammals.
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vangl2 disruption alters the biomechanics of late spinal Neurulation leading to spina bifida in mouse embryos
Disease Models & Mechanisms, 2018Co-Authors: Gabriel L Galea, Nicholas D E Greene, Oleksandr Nychyk, Matteo A Mole, Dale Moulding, Dawn Savery, Evanthia Nikolopoulou, Deborah J Henderson, Andrew J CoppAbstract:ABSTRACT Human mutations in the planar cell polarity component VANGL2 are associated with the neural tube defect spina bifida. Homozygous Vangl2 mutation in mice prevents initiation of neural tube closure, precluding analysis of its subsequent roles in Neurulation. Spinal Neurulation involves rostral-to-caudal ‘zippering’ until completion of closure is imminent, when a caudal-to-rostral closure point, ‘Closure 5’, arises at the caudal-most extremity of the posterior neuropore (PNP). Here, we used Grhl3 Cre to delete Vangl2 in the surface ectoderm (SE) throughout Neurulation and in an increasing proportion of PNP neuroepithelial cells at late Neurulation stages. This deletion impaired PNP closure after the ∼25-somite stage and resulted in caudal spina bifida in 67% of Grhl3 Cre/+ Vangl2 Fl/Fl embryos. In the dorsal SE, Vangl2 deletion diminished rostrocaudal cell body orientation, but not directional polarisation of cell divisions. In the PNP, Vangl2 disruption diminished mediolateral polarisation of apical neuroepithelial F-actin profiles and resulted in eversion of the caudal PNP. This eversion prevented elevation of the caudal PNP neural folds, which in control embryos is associated with formation of Closure 5 around the 25-somite stage. Closure 5 formation in control embryos is associated with a reduction in mechanical stress withstood at the main zippering point, as inferred from the magnitude of neural fold separation following zippering point laser ablation. This stress accommodation did not happen in Vangl2-disrupted embryos. Thus, disruption of Vangl2-dependent planar-polarised processes in the PNP neuroepithelium and SE preclude zippering point biomechanical accommodation associated with Closure 5 formation at the completion of PNP closure.
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the genetic basis of mammalian Neurulation
Nature Reviews Genetics, 2003Co-Authors: Andrew J Copp, Nicholas D E Greene, Jennifer N MurdochAbstract:More than 80 mutant mouse genes disrupt Neurulation and allow an in-depth analysis of the underlying developmental mechanisms. Although many of the genetic mutants have been studied in only rudimentary detail, several molecular pathways can already be identified as crucial for normal Neurulation. These include the planar cell-polarity pathway, which is required for the initiation of neural tube closure, and the sonic hedgehog signalling pathway that regulates neural plate bending. Mutant mice also offer an opportunity to unravel the mechanisms by which folic acid prevents neural tube defects, and to develop new therapies for folate-resistant defects.
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bending of the neural plate during mouse spinal Neurulation is independent of actin microfilaments
Developmental Dynamics, 1999Co-Authors: Patricia Ybotgonzalez, Andrew J CoppAbstract:To examine the role of actin microfilaments in mouse spinal Neurulation, we stained cryosections of E8.5-10.5 CBA/Ca em- bryos with FITC-phalloidin. Microfilaments are present in the apical region of all cells through- out the neuroepithelium, irrespective of whether they are involved in bending of the neural plate. Disruption of the microfilaments with cytochala- sin D inhibited closure of the cranial neural folds in cultured embryos, even at the lowest concentra- tions tested, and prevented the initiation of spi- nal Neurulation (Closure 1) at higher concentra- tions. In contrast, closure of the posterior neuropore was resistant to cytochalasin D at the highest concentrations tested. Phalloidin stain- ing and transmission electron microscopy con- firmed that cytochalasin D is effective in disassem- bling microfilaments in spinal neuroepithelial cells. We conclude that spinal neural tube closure does not require microfilament function, in con- trast to cranial Neurulation which is strongly microfilament-dependent. Histological examina- tion of cytochalasin D-treated embryos revealed that bending at hinge points, both in the midline (MHP) and dorsolaterally (DLHPs), continues in the absence of microfilaments, whereas the rigid- ity of non-bending regions of the neural plate is lost. This suggests that spinal Neurulation can continue in the presence of cytochalasin D largely as a result of intrinsic bending of the neural plate at hinge points. Cytochalasin D treatment is a useful tool for revealing the localisation of hinge points in the neural plate. Analysis of treated embryos demonstrates a transition, along the spinal axis, from closure solely involving midline bending, at high levels of the spinal axis, to closure solely involving dorsolateral bending, low in the spinal region. These findings support the idea of mechanistic heterogeneity in mouse neu- rulation, along the body axis, and demonstrate that contraction of actin microfilaments is not obligatory for epithelial bending during embry- onic morphogenesis. Dev Dyn 1999;215:273-283.
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regional differences in morphogenesis of the neuroepithelium suggest multiple mechanisms of spinal Neurulation in the mouse
Anatomy and Embryology, 1996Co-Authors: Alisa S W Shum, Andrew J CoppAbstract:A study of neuroepithelial morphogenesis in the mouse embryo has identified three modes of neural tube formation that occur consecutively as Neurulation progresses along the spinal region. The three modes of Neurulation differ in the extent to which the neuroepithelium exhibits formation of ‘hinge points’, i.e. localised bending owing to reduction in apical surface area. In Mode 1, bending occurs only in the neuroepithelium overlying the notochord, creating a median hinge point. The neural folds remain straight along both apical and basal surfaces, resulting in a neural tube with a slit-shaped lumen. In Mode 2, the neuroepithelium forms paired dorsolateral hinge points, as well as a median hinge point, whereas the remaining portions of the neuroepithelium do not bend. This produces a neural tube with a diamond-shaped lumen. In Mode 3 Neurulation, the entire neuroepithelium exhibits bending, so that the cells specific hinge points are not discernible; the resulting neural tube has a circular lumen. The three modes of Neurulation are present in all three strains of mice studied: C57BL/6, CBA/Ca and curly tail, a mutant predisposed to neural tube defects. However, curly tail embryos exhibit a delay in transition from Mode 2 to Mode 3, preceding faulty closure of the posterior neuropore. This heterogeneity of Neurulation morphogenesis in the mouse embryo indicates that the underlying mechanisms may vary along the body axis. Specifically, we suggest that Mode 1 Neurulation is driven largely by forces generated extrinsic to the neuroepithelium, in adjacent tissues, whereas Mode 3 Neurulation is dependent primarily on forces generated intrinsic to the neuroepithelium. Down the body axis, there is a gradual decrease in the area of ectoderm involved in neural induction and, as Neurulation reaches lower spinal levels, the newly induced neural plate exhibits marked indentation from the time of its first appearance. The transition from primary Neurulation (neural folding of Mode 3 type) to secondary Neurulation (neural tube formation by cavitation) appears to be a smooth continuation of this trend, with loss of contact between the newly induced neuroepithelium and the outside of the embryo.
Kyuchang Wang - One of the best experts on this subject based on the ideXlab platform.
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secondary Neurulation of human embryos morphological changes and the expression of neuronal antigens
Childs Nervous System, 2014Co-Authors: Hee-jin Yang, Kyuchang WangAbstract:Purpose The morphological changes and expression patterns of neuronal antigens of human embryos, obtained from the therapeutic termination of pregnancy or from surgical procedures, were analyzed in order to characterize the secondary Neurulation.
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pathoembryogenesis of terminal myelocystocele terminal balloon in secondary Neurulation of the chick embryo
Childs Nervous System, 2013Co-Authors: Sunghye Park, Dachling Pang, Jung Won Choi, Kyuchang WangAbstract:Purpose Terminal myelocystocele (TMC) is thought to be caused by a misstep during secondary Neurulation. However, due to the paucity of data on secondary Neurulation and the rarity of TMC, proofs of this pathogenetic mechanism are unavailable. Based on a previous observation that TMC resembles a step of secondary Neurulation in chick, a closer look was taken at secondary Neurulation of chick embryos focusing on the cerebrospinal fluid-filled distal neural tube (terminal balloon).
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expression of neuronal markers in the secondary Neurulation of chick embryos
Childs Nervous System, 2007Co-Authors: Younam Chung, Hee-jin Yang, Kyuchang WangAbstract:The goal of our study was to evaluate the expression patterns of neuronal antigens during the process of secondary Neurulation. Chick embryos of Hamburger and Hamilton stages 16, 18, 20, 22, 24, 26, 30, 35, 40, and 45 were harvested, and tail sections were processed for neuronal antigen studies. The areas and periods showing positive reactions for each antigen are as follows: neuronal cell adhesion molecule (N-CAM): the secondary neural tube and notochord from stages 18 to 26 and the germinal and mantle layers from stages 30 to 45; synaptophysin: the caudal cell mass, secondary neural tube, and notochord from stages 22 to 26, the germinal and mantle layers from stages 30 to 45, and the marginal layer at the later stages of development; neurofilament-associated protein (3A10): the dorsal white matter, dorsal root ganglion, and scattered cells around the germinal layer from stages 35 to 45; and neuronal nuclear-specific protein (NeuN): the mantle layer at stage 35, which shows decreased reaction at stages 40 and 45; islet-1: no remarkable staining on the caudal cell mass or on the other neural structures at all stages. Our results indicate that neuronal markers of the secondary Neurulation in chick embryos have their own chronological patterns of expression. At early stages of secondary Neurulation, N-CAM and synaptophysin are thought to modulate the differentiation of structures derived from the caudal cell mass. At later stages, N-CAM, synaptophysin, 3A10, and NeuN seem to be involved in the maturation of the caudal spinal cord.
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Cytokinetics of secondary Neurulation in chick embryos: Hamburger and Hamilton stages 16–45
Childs Nervous System, 2006Co-Authors: Hee-jin Yang, Kyuchang WangAbstract:Objectives In an attempt to understand the events in the secondary Neurulation in embryonic stage, we investigated cytokinetic changes in the tail bud of normal developing chick embryos.
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neural differentiation of caudal cell mass secondary Neurulation in chick embryos hamburger and hamilton stages 16 45
Developmental Brain Research, 2003Co-Authors: Hee-jin Yang, Kyuchang WangAbstract:In an attempt to understand the events in the secondary Neurulation in embryonic stage, we investigated morphological changes in the tail bud of normal developing chick embryos. Hamburger and Hamilton stage 16-45 embryos were harvested and processed for light microscopic studies. The secondary neural tube is formed by aggregation of the caudal cell mass. Cells are arranged into a cord-like mass (medullary cord), which is continuous with the primary neural tube. Multiple small cavities develop in the medullary cord, and these cavities coalesce into one single lumen. The process of coalescence is completed by stage 35, and the whole neural tube is transformed into one tube with a single continuous lumen. At this stage, the terminal portion of the neural tube is bulged dorsally. Thereafter, the caudal portion of the neural tube regresses, and the proximal portion develops into normal spinal cord. Transient occlusion of the central canal was observed at stage 40 in one sample. The sequence of events elucidated in this study can be used as base-line data for experiments concerning congenital malformations involving secondary Neurulation.
Gary C Schoenwolf - One of the best experts on this subject based on the ideXlab platform.
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Contributions of the chick embryo and experimental embryology to understanding the cellular mechanisms of Neurulation.
The International journal of developmental biology, 2020Co-Authors: Gary C SchoenwolfAbstract:The chick embryo has served as a workhorse for experimental embryological studies designed to elucidate mechanisms underlying Neurulation, the process that forms the neural tube, the rudiment of the entire adult central nervous system. Early chick embryos developing in whole-embryo culture can be readily manipulated in cut-and-paste-type experiments, and this attribute makes this model system unparalleled for studying the morphogenesis of embryos and their organ rudiments. How the chick embryo and experimental embryology have contributed to our understanding of critical events of Neurulation are summarized.
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Assessing the contributions of gene products to the form-shaping events of Neurulation: a transgenic approach in chick.
Genesis, 2003Co-Authors: Jean Francois Colas, Gary C SchoenwolfAbstract:Summary: Most of our current knowledge on the tissue and cellular basis of Neurulation in amniotes has been gained using the chick embryo as an experimental model system. Gene manipulation during chick Neurulation has been difficult, greatly limiting our ability to assess the contribution of gene products to the tissue and cellular behaviors of Neurulation. Using electroporation, we have developed a simple and reliable method for expressing transgenes in the ectoderm of the neural folds of chick embryos developing in whole-embryo culture. Sense- or antisense-expressing plasmids are electroporated, resulting in gain or loss of gene function, respectively. The morphogenesis of transgenic tissues was compared to the morphogenesis of contralateral wildtype tissues as Neurulation was taking place. As a proof of principle, we present a functional analysis of the chick gene encoding Cartilage Linking Protein 1 (CRTL1), identified as a candidate Neurulation gene using subtractive hybridization. This experimental approach provides a much-needed innovation for studying the mechanisms by which genes influence Neurulation and reveals here important contributions of CRTL1 to the formation of the neural folds. genesis 37:64–75, 2003. © 2003 Wiley-Liss, Inc.
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Localization of cartilage linking protein 1 during primary Neurulation in the chick embryo.
Brain research. Developmental brain research, 2003Co-Authors: Jean Francois Colas, Gary C SchoenwolfAbstract:Primary Neurulation is a form-shaping event during the early development of the vertebrate embryo in which the neural plate is rolled up into the neural tube, the rudiment of the central nervous system. In an effort to identify genes specifically expressed in tissues lateral to the chick neural plate--tissues known to generate extrinsic forces for primary Neurulation--we designed a subtractive scheme and identified a positive clone as the gene encoding chick cartilage linking protein 1 (CRTL1). CRTL1 (also known as link protein) is a small glycoprotein of the extracellular matrix that was originally identified for its role in stabilizing aggregates of aggrecan and hyaluronan in cartilage. In addition to being expressed in cartilage, CRTL1 is also immunolocalized in several noncartilaginous tissues as assessed with the 4B6 monoclonal antibody. Using the 4B6 antibody and the G9 riboprobe derived from our subtraction, we report the detailed distribution of CRTL1 protein and crtl1 transcripts during primary Neurulation in chick embryos. This report emphasizes and briefly discusses important differences between the RNA expression pattern and the domains of accumulation of the protein. CRTL1 prominently accumulates in the basal lamina of the epidermal ectoderm just lateral to the neural plate. Based on the crucial role of the interface between this tissue and the neuroepithelium in the formation of the neural folds, and because of the biophysical role of hyaluronan in tissue morphogenesis, we propose that crtl1 represents is an excellent candidate Neurulation gene, worthy of further study.
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towards a cellular and molecular understanding of Neurulation
Developmental Dynamics, 2001Co-Authors: Jean Francois Colas, Gary C SchoenwolfAbstract:Neurulation occurs during the early embryogenesis of chordates, and it results in the formation of the neural tube, a dorsal hollow nerve cord that constitutes the rudiment of the entire adult central nervous system. The goal of studies on Neurulation is to understand its tissue, cellular and molecular basis, as well as how Neurulation is perturbed during the formation of neural tube defects. The tissue basis of Neurulation consists of a series of coordinated morphogenetic movements within the primitive streak (e.g., regression of Hensen's node) and nascent primary germ layers formed during gastrulation. Signaling occurs between Hensen's node and the nascent ectoderm, initiating Neurulation by inducing the neural plate (i.e., actually, by suppressing development of the epidermal ectoderm). Tissue movements subsequently result in shaping and bending of the neural plate and closure of the neural groove. The cellular basis of the tissue movements of Neurulation consists of changes in the behavior of the constituent cells; namely, changes in cell number, position, shape, size and adhesion. Neurulation, like any morphogenetic event, occurs within the milieu of generic biophysical determinants of form present in all living tissues. Such forces govern and to some degree control morphogenesis in a tissue-autonomous manner. The molecular basis of Neurulation remains largely unknown, but we suggest that Neurulation genes have evolved to work in concert with such determinants, so that appropriate changes occur in the behaviors of the correct populations of cells at the correct time, maximizing the efficiency of Neurulation and leading to heritable species- and axial-differences in this process. In this article, we review the tissue and cellular basis of Neurulation and provide strategies to determine its molecular basis. We expect that such strategies will lead to the identification in the near future of critical Neurulation genes, genes that when mutated perturb Neurulation in a highly specific and predictable fashion and cause Neurulation defects, thereby contributing to the formation of neural tube defects. © 2001 Wiley-Liss, Inc.
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Neurulation coming to closure
Trends in Neurosciences, 1997Co-Authors: Jodi L Smith, Gary C SchoenwolfAbstract:Abstract Neurulation is a morphogenetic event par excellence. During this highly choreographed four-dimensional process, a flat sheet of ectoderm is transformed into an elongated tubular rudiment, the neural tube, which exhibits rostro-caudal and mediolateral regionalization. Many tissues interact during Neurulation to induce and regionalize the neuroectoderm and to produce the morphogenetic forces that drive Neurulation. Such forces are generated by fundamental cell behaviors such as changes in cell shape, position and number. In addition, morphoregulatory molecules expressed during Neurulation underlie induction and patterning of the forming neuraxis. Despite recent advances in our understanding of Neurulation, neural tube defects continue to be a major health care concern. Further research, utilizing a panoply of approaches, is necessary to resolve this issue. Thus, although we are beginning to come to closure in terms of understanding the cellular and molecular mechanisms responsible for normal neural tube formation, `coming to closure' is exactly the problem that requires resolution to prevent these devastating birth defects.
Martin Catala - One of the best experts on this subject based on the ideXlab platform.
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junctional Neurulation a unique developmental program shaping a discrete region of the spinal cord highly susceptible to neural tube defects
The Journal of Neuroscience, 2014Co-Authors: Alwyn Dady, Emmanuelle Havis, Virginie Escriou, Martin Catala, Jeanloup DubandAbstract:In higher vertebrates, the primordium of the nervous system, the neural tube, is shaped along the rostrocaudal axis through two consecutive, radically different processes referred to as primary and secondary Neurulation. Failures in Neurulation lead to severe anomalies of the nervous system, called neural tube defects (NTDs), which are among the most common congenital malformations in humans. Mechanisms causing NTDs in humans remain ill-defined. Of particular interest, the thoracolumbar region, which encompasses many NTD cases in the spine, corresponds to the junction between primary and secondary Neurulations. Elucidating which developmental processes operate during Neurulation in this region is therefore pivotal to unraveling the etiology of NTDs. Here, using the chick embryo as a model, we show that, at the junction, the neural tube is elaborated by a unique developmental program involving concerted movements of elevation and folding combined with local cell ingression and accretion. This process ensures the topological continuity between the primary and secondary neural tubes while supplying all neural progenitors of both the junctional and secondary neural tubes. Because it is distinct from the other Neurulation events, we term this phenomenon junctional Neurulation. Moreover, the planar-cell-polarity member, Prickle-1 , is recruited specifically during junctional Neurulation and its misexpression within a limited time period suffices to cause anomalies that phenocopy lower spine NTDs in human. Our study thus provides a molecular and cellular basis for understanding the causality of NTD prevalence in humans and ascribes to Prickle-1 a critical role in lower spinal cord formation.
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neural crest ontogeny during secondary Neurulation a gene expression pattern study in the chick embryo
The International Journal of Developmental Biology, 2009Co-Authors: Liliana Osorio, Marie Aimee Teillet, Isabel Palmeirim, Martin CatalaAbstract:In the prospective lumbo-sacral region of the chick embryo, Neurulation is achieved by cavitation of the medullary cord, a process called secondary Neurulation. Neural crest cells (NCC) are generated in this region and they give rise to the same types of derivatives as in more rostral parts of the trunk where Neurulation occurs by dorsal fusion of the neural plate borders (primary Neurulation). However, no molecular data were available concerning the different steps of their ontogeny. We thus performed a detailed expression study of molecular players likely to participate in the generation of secondary NCC in chick embryos between Hamburger and Hamilton stages 18-20 (HH18-20) at the level of somites 30 to 43. We found that specification of secondary NCC involves, as in primary Neurulation, the activity of several transcription factors such as Pax3, Pax7, Snail2, FoxD3 and Sox9, which are all expressed in the dorsal secondary neural tube as soon as full cavitation is achieved. Moreover, once specification has occurred, emigration of NCC from the dorsal neuroepithelium starts facing early dissociating somites and involves a series of changes in cell shape and adhesion, as well as interactions with the extracellular matrix. Furthermore, Bmp4 and Wnt1 expression precedes the detection of migratory secondary NCC and is coincident with maturation of adjacent somites. Altogether, this first study of molecular aspects of secondary NCC ontogeny has revealed that the mechanisms of neural crest generation occurring along the trunk region of the chick embryo are generally conserved and independent of the type of Neurulation involved.
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Neurulation in amniote vertebrates: a novel view deduced from the use of quail-chick chimeras.
The International Journal of Developmental Biology, 1998Co-Authors: N M Le Douarin, Marie Aimee Teillet, Martin CatalaAbstract:Two apparently different mechanisms successively contribute to the formation of the neural tube in the avian embryo: bending of the neural plate during the primary Neurulation in the cephalo-cervico-thoracic region and cavitation of the medullary cord during the secondary Neurulation in the lumbo-sacral region. During both these processes, gastrulation continues by the caudal regression of Hensen's node--also called cordoneural hinge in the secondary Neurulation. Labeling of Hensen's node or cordoneural hinge by the quail chick marker system revealed that this structure, which is the equivalent of the dorsal blastoporal lip of the Amphibian embryo, i.e., of the Spemann's organizer, gives rise to the midline cells of the three germ layers: the floor plate of the neural tube, the notocord and the dorsal cells of the intestinal endoderm. Caudally to the organizer, both in primary and secondary Neurulation, the presumptive territory of the alar plates of the future neural tube overlies the precursors of the paraxial mesoderm. Regression of Hensen's node bisects the ectoderm in two bilateral neural plates leaving in its wake the floor plate, the notocord and the dorsal endoderm.
Jeanloup Duband - One of the best experts on this subject based on the ideXlab platform.
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junctional Neurulation a unique developmental program shaping a discrete region of the spinal cord highly susceptible to neural tube defects
The Journal of Neuroscience, 2014Co-Authors: Alwyn Dady, Emmanuelle Havis, Virginie Escriou, Martin Catala, Jeanloup DubandAbstract:In higher vertebrates, the primordium of the nervous system, the neural tube, is shaped along the rostrocaudal axis through two consecutive, radically different processes referred to as primary and secondary Neurulation. Failures in Neurulation lead to severe anomalies of the nervous system, called neural tube defects (NTDs), which are among the most common congenital malformations in humans. Mechanisms causing NTDs in humans remain ill-defined. Of particular interest, the thoracolumbar region, which encompasses many NTD cases in the spine, corresponds to the junction between primary and secondary Neurulations. Elucidating which developmental processes operate during Neurulation in this region is therefore pivotal to unraveling the etiology of NTDs. Here, using the chick embryo as a model, we show that, at the junction, the neural tube is elaborated by a unique developmental program involving concerted movements of elevation and folding combined with local cell ingression and accretion. This process ensures the topological continuity between the primary and secondary neural tubes while supplying all neural progenitors of both the junctional and secondary neural tubes. Because it is distinct from the other Neurulation events, we term this phenomenon junctional Neurulation. Moreover, the planar-cell-polarity member, Prickle-1 , is recruited specifically during junctional Neurulation and its misexpression within a limited time period suffices to cause anomalies that phenocopy lower spine NTDs in human. Our study thus provides a molecular and cellular basis for understanding the causality of NTD prevalence in humans and ascribes to Prickle-1 a critical role in lower spinal cord formation.
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timing and kinetics of e to n cadherin switch during Neurulation in the avian embryo
Developmental Dynamics, 2012Co-Authors: Alwyn Dady, Jeanloup Duband, Cedrine BlavetAbstract:Background: During embryonic development, cadherin switches are correlated with tissue remodelings, such as epithelium-to-mesenchyme transition (EMT). An E- to N-cadherin switch also occurs during neurogenesis, but this is not accompanied with EMT. The biological significance of this switch is currently unknown. Results: We analyzed the timing and kinetics of the E- to N-cadherin switch during early neural induction and Neurulation in the chick embryo, in relation to the patterns of their transcriptional regulators. We found that deployment of the E- to N-cadherin switch program varies considerably along the embryonic axis. Rostrally in regions of primary Neurulation, it occurs progressively both in time and space in a manner that appears neither in connection with morphological transformation of neural epithelial cells nor in synchrony with movements of Neurulation. Caudally, in regions of secondary Neurulation, neurogenesis was not associated with cadherin switch as N-cadherin pre-existed before formation of the neural tube. We also found that, during neural development, cadherin switch is orchestrated by a set of transcriptional regulators distinct from those involved in EMT. Conclusions: Our results indicate that cadherin switch correlates with the partition of the neurectoderm into its three main populations: ectoderm, neural crest, and neural tube. Developmental Dynamics 241:1333–1349, 2012. © 2012 Wiley Periodicals, Inc.