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John L.r. Rubenstein - One of the best experts on this subject based on the ideXlab platform.
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fgf and shh signals control dopaminergic and serotonergic cell fate in the anterior Neural Plate
Cell, 1998Co-Authors: Weilan Ye, Kenji Shimamura, John L.r. Rubenstein, Mary A Hynes, Arnon RosenthalAbstract:Abstract During development, distinct classes of neurons are specified in precise locations along the dorso–ventral and anterior–posterior axes of the Neural tube. We provide evidence that intersections of Shh, which is expressed along the ventral Neural tube, and FGF8, which is locally produced at the mid/hindbrain boundary and in the rostral forebrain, create induction sites for dopaminergic neurons in the midbrain and forebrain. The same intersection, when preceded by a third signal, FGF4, which is expressed in the primitive streak, defines an inductive center for hindbrain 5-HT neurons. These findings illustrate that cell patterning in the Neural Plate is a multistep process in which early inducers, which initially divide the Neural Plate into crude compartments, are replaced by multiple local organizing centers, which specify distinct neuronal cell types within these compartments.
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regionalization of the prosencephalic Neural Plate
Annual Review of Neuroscience, 1998Co-Authors: John L.r. Rubenstein, Kenji Shimamura, Salvador Martinez, Luis PuellesAbstract:▪ Abstract Recent embryological studies are beginning to establish that the underlying organization of the forebrain may be reduced to relatively simple elements that are common to all vertebrates. We begin this chapter by reviewing studies that describe the similarities in prospective fate and molecular organization of the developing Neural Plate in fish, frogs, chickens, and mice. The chapter next addresses mechanisms that regulate regional specification in the anterior central nervous system. There is now evidence that the axial mesendoderm anterior to the notochord (the prechordal Plate) has a central role in induction of the floor and basal Plate primordia (hypothalamus) of the forebrain. Patterning of the anterolateral Neural Plate (telencephalon) may be regulated by FGF8 produced in the anterior Neural ridge. Thus, the synthesis of information from fate mapping and experimental embryological and genetic studies is illuminating the mechanisms that generate the different components of the forebrain.
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inductive interactions direct early regionalization of the mouse forebrain
Development, 1997Co-Authors: Kenji Shimamura, John L.r. RubensteinAbstract:The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in Neural Plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic Neural Plate. Molecular properties of the medial Neural Plate are regulated by the prechordal Plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral Neural Plate is regulated by non-Neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior Neural ridge regulates patterning of the anterior Neural Plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior Neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior Neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral Neural Plate derivatives. Furthermore, we provide evidence that the Neural Plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal Plate, Sonic Hedgehog, the anterior Neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the Neural Plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior Neural ridge, further define the regional organization.
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longitudinal organization of the anterior Neural Plate and Neural tube
Development, 1995Co-Authors: Kenji Shimamura, Salvador Martinez, Luis Puelles, Dennis J Hartigan, John L.r. RubensteinAbstract:Over the last century, several morphological models of forebrain organization have been proposed that hypothesize alternative topological solutions for the relationships of the histogenic primordia. Central to all of these models are their definitions of the longitudinal axis and the longitudinal organization of the Neural Plate and Neural tube. To understand the longitudinal organization of the anterior brain, we have sought to identify molecular properties that are continuous along the entire longitudinal axis of the embryonic CNS. In this essay, we describe studies of the expression of several genes in the mouse between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide evidence for the trajectory of the anteriorposterior axis and the longitudinal organization of the anterior CNS. Specifically, we report that the expression of noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are present along the entire CNS axis. Within the forebrain, the expression of these genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions in the Neural Plate and tube. We demonstrate that the earliest longitudinal axon pathways of the forebrain are spatially correlated with the longitudinal domain defined by Nkx2.2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic Neural Plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the Neural Plate. SUMMARY
Eglantine Heude - One of the best experts on this subject based on the ideXlab platform.
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Posterior axis formation requires Dlx5/Dlx6 expression at the Neural Plate border
PLoS ONE, 2019Co-Authors: Nicolas Narboux-nême, Giovanni Levi, Marc Ekker, Eglantine HeudeAbstract:Neural tube defects (NTDs), one of the most common birth defects in human, present a multifactorial etiology with a poorly defined genetic component. The Dlx5 and Dlx6 bigenic cluster encodes two evolutionary conserved homeodomain transcription factors, which are necessary for proper vertebrate development. It has been shown that Dlx5/6 genes are essential for anterior Neural tube closure, however their role in the formation of the posterior structures has never been described. Here, we show that Dlx5/6 expression is required during vertebrate posterior axis formation. Dlx5 presents a similar expression pattern in Neural Plate border cells during posterior neurulation of zebrafish and mouse. Dlx5/6-inactivation in the mouse results in a phenotype reminiscent of NTDs characterized by open thoracic and lumbar vertebral arches and failure of epaxial muscle formation at the dorsal midline. The dlx5a/6a zebrafish morphants present posterior NTDs associated with abnormal delamination of Neural crest cells showing altered expression of cell adhesion molecules and defects of motoneuronal development. Our findings provide new molecular leads to decipher the mechanisms of vertebrate posterior neurulation and might help to gather a better understanding of human congenital NTDs etiology.
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posterior axis formation requires dlx5 dlx6 expression at the Neural Plate border
bioRxiv, 2018Co-Authors: Nicolas Narbouxneme, Giovanni Levi, Marc Ekker, Eglantine HeudeAbstract:Neural tube defects (NTDs), one of the most common birth defects in human, present a multifactorial etiology with a poorly defined genetic component. The Dlx5 and Dlx6 bigenic cluster encodes two evolutionary conserved homeodomain transcription factors, which are necessary for proper vertebrate development. It has been shown that Dlx5/6 genes are essential for anterior Neural tube closure, however their role in the formation of the posterior structures has never been described. Here, we show that Dlx5/6 expression is required during vertebrate posterior axis formation. Dlx5 presents a similar expression pattern in Neural Plate border cells during posterior neurulation of zebrafish and mouse. Dlx5/6-inactivation in the mouse results in a phenotype reminiscent of NTDs characterized by open thoracic and lumbar vertebral arches and failure of epaxial muscle formation at the dorsal midline. The dlx5a/6a zebrafish morphants present posterior NTDs associated with abnormal delamination of Neural crest cells showing altered expression of cell adhesion molecules and defects of motoneuronal development. Our findings provide new molecular leads to decipher the mechanisms of vertebrate posterior neurulation and might help to gather a better understanding of human congenital NTDs etiology.
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posterior Neural tube closure depends on dlx5 dlx6 expression at the Neural Plate border
bioRxiv, 2018Co-Authors: Nicolas Narbouxneme, Giovanni Levi, Marc Ekker, Eglantine HeudeAbstract:Neural tube defects (NTDs), one of the most common birth defects in human, present a multifactorial etiology with a poorly defined genetic component. The Dlx5 and Dlx6 bigenic cluster encodes two evolutionary conserved homeodomain transcription factors, which are necessary for proper vertebrate development. It has been shown that Dlx5/6 genes are essential for anterior Neural tube closure, however their role in the formation of the posterior Neural tube has never been described. Here, we show that Dlx5/6 expression is required during vertebrate posterior Neural tube closure. Dlx5 presents a similar expression pattern in Neural Plate border cells during zebrafish and mouse posterior neurulation. Dlx5/6-inactivation in mouse results in a phenotype reminiscent of NTDs characterized by open thoracic and lumbar vertebral arches and failure of epaxial muscle formation at the dorsal midline. Similarly, dlx5a/6a zebrafish morphants show defects of posterior Neural tube closure accompanied by aberrant delamination of Neural crest cells with altered expression of cell adhesion molecules and defects of motoneuron formation. Our findings provide new molecular leads to decipher the mechanisms involved during vertebrate posterior neurulation for a better understanding of the etiology of human congenital NTDs and other midline field defects.
Kenji Shimamura - One of the best experts on this subject based on the ideXlab platform.
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early subdivisions in the Neural Plate define distinct competence for inductive signals
Development, 2002Co-Authors: Daisuke Kobayashi, Makoto Kobayashi, Ken Matsumoto, Toshihiko Ogura, Masato Nakafuku, Kenji ShimamuraAbstract:Regionalization of the embryonic brain is achieved through multi-step processes that operate sequentially and/or simultaneously. Localized sources of various signaling molecules act as organizing centers that pattern neighboring fields to create molecularly distinct domains. We investigated the mechanisms underlying the regionally distinct competence for two such organizing signals, Fibroblast growth factor 8 (Fgf8) and Sonic hedgehog (Shh), using chick embryos. First, we demonstrated that FGF receptor 1 (Fgfr1) and Fgfr3, expressed differentially in the developing brain, possess an equivalent potential to induce the regionally distinct Fgf8-responsive genes, depending on the anterior-posterior dimension of the brain. Next we found that homeodomain transcription factors Six3 and Irx3 can alter the regional responses to both Fgf8 and Shh in the forebrain. Six3 confers the ability to express Bf1 , a gene essential for the telencephalon and eye development, and Nkx2.1 , which is required for development of the hypothalamus. In contrast, Irx3 confers the ability to express En2 and Nkx6.1 in response to Fgf8 and Shh, respectively. Furthermore, an alteration in the region-specific response to Fgf8 upon misexpression of Irx3 resulted in transformation of diencephalic and possibly telencephalic tissues into the optic tectum. Finally, we demonstrated that Six3 and Irx3 can mutually repress their expression, which may contribute to the establishment of their complementary expression domains in the Neural Plate. These repressive interactions are specific, as Six3 did not repress Gbx2 , and Irx3 did not disturb Otx2 expression. These findings provide evidence that the early embryonic forebrain is demarcated into two domains with distinct genetic programs, which argues against the authentic telen-diencephalic subdivision.
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fgf and shh signals control dopaminergic and serotonergic cell fate in the anterior Neural Plate
Cell, 1998Co-Authors: Weilan Ye, Kenji Shimamura, John L.r. Rubenstein, Mary A Hynes, Arnon RosenthalAbstract:Abstract During development, distinct classes of neurons are specified in precise locations along the dorso–ventral and anterior–posterior axes of the Neural tube. We provide evidence that intersections of Shh, which is expressed along the ventral Neural tube, and FGF8, which is locally produced at the mid/hindbrain boundary and in the rostral forebrain, create induction sites for dopaminergic neurons in the midbrain and forebrain. The same intersection, when preceded by a third signal, FGF4, which is expressed in the primitive streak, defines an inductive center for hindbrain 5-HT neurons. These findings illustrate that cell patterning in the Neural Plate is a multistep process in which early inducers, which initially divide the Neural Plate into crude compartments, are replaced by multiple local organizing centers, which specify distinct neuronal cell types within these compartments.
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regionalization of the prosencephalic Neural Plate
Annual Review of Neuroscience, 1998Co-Authors: John L.r. Rubenstein, Kenji Shimamura, Salvador Martinez, Luis PuellesAbstract:▪ Abstract Recent embryological studies are beginning to establish that the underlying organization of the forebrain may be reduced to relatively simple elements that are common to all vertebrates. We begin this chapter by reviewing studies that describe the similarities in prospective fate and molecular organization of the developing Neural Plate in fish, frogs, chickens, and mice. The chapter next addresses mechanisms that regulate regional specification in the anterior central nervous system. There is now evidence that the axial mesendoderm anterior to the notochord (the prechordal Plate) has a central role in induction of the floor and basal Plate primordia (hypothalamus) of the forebrain. Patterning of the anterolateral Neural Plate (telencephalon) may be regulated by FGF8 produced in the anterior Neural ridge. Thus, the synthesis of information from fate mapping and experimental embryological and genetic studies is illuminating the mechanisms that generate the different components of the forebrain.
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inductive interactions direct early regionalization of the mouse forebrain
Development, 1997Co-Authors: Kenji Shimamura, John L.r. RubensteinAbstract:The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in Neural Plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic Neural Plate. Molecular properties of the medial Neural Plate are regulated by the prechordal Plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral Neural Plate is regulated by non-Neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior Neural ridge regulates patterning of the anterior Neural Plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior Neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior Neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral Neural Plate derivatives. Furthermore, we provide evidence that the Neural Plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal Plate, Sonic Hedgehog, the anterior Neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the Neural Plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior Neural ridge, further define the regional organization.
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longitudinal organization of the anterior Neural Plate and Neural tube
Development, 1995Co-Authors: Kenji Shimamura, Salvador Martinez, Luis Puelles, Dennis J Hartigan, John L.r. RubensteinAbstract:Over the last century, several morphological models of forebrain organization have been proposed that hypothesize alternative topological solutions for the relationships of the histogenic primordia. Central to all of these models are their definitions of the longitudinal axis and the longitudinal organization of the Neural Plate and Neural tube. To understand the longitudinal organization of the anterior brain, we have sought to identify molecular properties that are continuous along the entire longitudinal axis of the embryonic CNS. In this essay, we describe studies of the expression of several genes in the mouse between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide evidence for the trajectory of the anteriorposterior axis and the longitudinal organization of the anterior CNS. Specifically, we report that the expression of noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are present along the entire CNS axis. Within the forebrain, the expression of these genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions in the Neural Plate and tube. We demonstrate that the earliest longitudinal axon pathways of the forebrain are spatially correlated with the longitudinal domain defined by Nkx2.2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic Neural Plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the Neural Plate. SUMMARY
Gary C. Schoenwolf - One of the best experts on this subject based on the ideXlab platform.
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epidermal ectoderm is required for full elevation and for convergence during bending of the avian Neural Plate
Developmental Dynamics, 1997Co-Authors: Deborah A Hackett, Jodi L. Smith, Gary C. SchoenwolfAbstract:Previous studies suggest that bending of the Neural Plate requires the juxtapo- sition of Neural Plate and non-neuroepithelial tissues. The current study examines the role of one of these tissues, the epidermal ectoderm, in bending. Chick blastoderms were harvested from fertile eggs incubated for 24 hr and cultured dorsal-side-up on agar-albumen substrates. In one experiment, a rectangular flap of epidermal ectoderm on one side of each blastoderm was separated from underlying layers and gently re- flected onto the area opaca; a fragment of tung- sten wire was placed on top of the flap to hold it down and to prevent healing. Embryos were then allowed to develop in a humidified incubator for 2-18 hr. Asymmetric neurulation was observed between the operated and control sides as early as 2 hr after surgery. The amount of asymmetry was quantified in serial transverse sections from embryos collected 8 hr after surgery. Elevation of the lateral edge of the Neural Plate on the oper- ated side averaged one half to two thirds of that on the control side, and convergence of the oper- ated side around the dorsolateral hinge point toward the dorsal midline did not occur. These results demonstrate that epidermal ectoderm is required for full elevation and for convergence during bending. In another experiment, lateral epidermal ectoderm was removed, leaving only a medial strip consisting of both the epidermal component of the future Neural fold and flanking future epidermis. This experiment revealed that although epidermal ectoderm is necessary for full elevation and for convergence of the Neural folds, a medial strip of epidermal ectoderm is sufficient to drive bending. Collectively, these results further support the idea that neurulation is a multifactorial process driven by both intrin- sic and extrinsic factors acting in concert. Dev. Dyn. 1997;210:397-406. r 1997 Wiley-Liss, Inc.
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state of commitment of prospective Neural Plate and prospective mesoderm in late gastrula early neurula stages of avian embryos
Developmental Biology, 1997Co-Authors: Virginio Garciamartinez, Diana K Darnell, Carmen Lopezsanchez, Drazen Sosic, Eric N Olson, Gary C. SchoenwolfAbstract:Abstract We examined the ability of epiblast regions of known prospective fate from the late gastrula/early neurula stage of avian embryos to self-differentiate when placed heterotopically, testing their state of commitment. Three sites were examined: paranodal prospective Neural Plate ectoderm, containing cells fated to form a portion of the lateral wall of the Neural tube at essentially all rostrocaudal levels of the neuraxis; prospective mesoderm from the caudolateral epiblast, containing cells fated to ingress through the primitive streak and to form lateral Plate mesoderm; and prospective mesoderm from one level of the primitive streak, containing cells fated to continue ingressing and form paraxial mesoderm. Grafts from all sites exhibited plasticity. Grafts from the prospective Neural Plate ectoderm could readily substitute for regions of prospective mesoderm, when transplanted to either the epiblast or primitive streak, undergoing an epithelial–mesenchymal transition and, where appropriate, expressing paraxis, a gene expressed in paraxial mesoderm. Similarly, grafts containing prospective mesoderm from the epiblast could readily substitute for regions of the prospective Neural Plate ectoderm, undergoing convergent-extension movements characteristic of neuroectodermal cells and expressing appropriate genes such as Engrailed-2 and Hoxb-1. Grafts containing prospective mesoderm from the primitive streak could also incorporate into the Neural Plate and undergo convergence-extension movements of neurulation, although their principal contribution was to mesodermal and endodermal structures. Collectively, our results demonstrate that at the late gastrula/early neurula stage, germ layer-specific properties are not irrevocably fixed for prospective ectodermal and mesodermal regions of the blastoderm. Moreover, the signals responsible for the induction of these two tissue types must still be present and available at these late stages.
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cooperative model of epithelial shaping and bending during avian neurulation autonomous movements of the Neural Plate autonomous movements of the epidermis and interactions in the Neural Plate epidermis transition zone
Developmental Dynamics, 1995Co-Authors: J D Moury, Gary C. SchoenwolfAbstract:Morphogenetic movements during neurulation cause a tissue to change shape within the plane of the epithelium (e.g., conversion of the oval Neural Plate into the narrow spinal Plate and the wide brain Plate), cause bending out of the plane of the epithelium (e.g., raise the Neural folds and curl the Neural Plate into a tube), or contribute to both phenomena. In this study, pieces that contain Neural Plate alone, epidermis alone, or both tissues (with or without underlying tissues) are cut from chick embryos and allowed to develop for up to 24 hr. Examination of histological sections through such isolates allows analysis of the formation of Neural folds. When the Neural Plate/epidermis transition zone is disrupted, Neural folds do not form. Conversely, when the transition zone remains intact, Neural folds form. Neural folds form even when most of the medial Neural Plate and lateral epidermis has been removed, leaving only the isolated transition zone. These data indicate that the transition zone is both necessary and sufficient for the formation of Neural folds. The transition zone may play a number of roles in epithelial bending including organizing, focussing, and redirecting movements that are autonomous to the Neural Plate or epidermis. Time-lapse video recording, and sequential photographs allowed the documentation of such movements. Neural Plate isolates exhibit autonomous rostrocaudal lengthening and mediolateral narrowing. Isolated strips of epidermis exhibit autonomous movements which, unlike wound-healing movements, are unidirectional (mediad), and region-specific (beginning and reaching their greatest extent in the cranial region). Isolated pieces of Neural Plate or epidermis remain flat instead of bending, providing further evidence that the transition zone is necessary for the formation of Neural folds. © 1995 wiley-Liss, Inc.
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formation and patterning of the avian neuraxis one dozen hypotheses
Ciba Foundation symposium, 1994Co-Authors: Gary C. SchoenwolfAbstract:Formation of the neuraxis is dependent on cell-cell interactions and cell movements beginning during stages of gastrulation. Cell movements bring together new combinations of cells, allowing sequential inductive interactions to occur and leading to the specification of the Neural Plate and to its ultimate mediolateral (subsequently dorsoventral) and rostrocaudal patterning. Formation of the Neural Plate involves changes in the shape of its constituent cells and the first appearance of Neural-specific cell markers. Shortly after the Neural Plate forms it undergoes 'shaping', in which the pseudostratified columnar epithelium constituting the Neural Plate thickens apicobasally, narrows transversely and extends longitudinally. Shaping is driven by three principal intrinsic types of cell behaviour: changes in cell shape, position and number. The next stage of neurulation begins while shaping is underway--bending of the Neural Plate. Bending involves two main processes, furrowing and folding. Furrowing of the Neural Plate is associated with the formation of the hinge points; these are localized, longitudinal areas where the neuroepithelium is attached to adjacent tissues and where wedging of neuroepithelial cells occurs. Cell wedging in the median hinge point occurs as a result of inductive interactions with the notochord; such wedging drives furrowing, thereby facilitating subsequent folding. Folding of the Neural Plate requires extrinsic forces generated largely by the surface ectoderm. Types of cell behaviour that could provide such forces include changes in cell shape, position and number. As a result of shaping and bending of the Neural Plate, the Neural folds are brought into apposition in the dorsal midline. Final closure of the Neural groove is mediated by cell surface glycoconjugates coating the apical surfaces of the Neural folds. Patterning of the neuraxis begins during shaping of the Neural Plate and continues throughout stages of neurulation and into early postneurula stages. Patterning probably involves inductive interactions with adjacent tissues and the expression of putative positional identity genes such as homeobox-containing genes.
Andrea Streit - One of the best experts on this subject based on the ideXlab platform.
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calfacilitin is a calcium channel modulator essential for initiation of Neural Plate development
Nature Communications, 2013Co-Authors: Costis Papanayotou, Irene De Almeida, Nidia M M Oliveira, Songqing Lu, Alex Shaw, Guojun Sheng, Ping Liao, Eleni Kougioumtzidou, Andrea StreitAbstract:Calcium fluxes have been implicated in the specification of the vertebrate embryonic nervous system for some time, but how these fluxes are regulated and how they relate to the rest of the Neural induction cascade is unknown. Here we describe Calfacilitin, a transmembrane calcium channel facilitator that increases calcium flux by generating a larger window current and slowing inactivation of the L-type CaV1.2 channel. Calfacilitin binds to this channel and is co-expressed with it in the embryo. Regulation of intracellular calcium by Calfacilitin is required for expression of the Neural Plate specifiers Geminin and Sox2 and for Neural Plate formation. Loss-of-function of Calfacilitin can be rescued by ionomycin, which increases intracellular calcium. Our results elucidate the role of calcium fluxes in early Neural development and uncover a new factor in the modulation of calcium signalling.
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cell communication with the Neural Plate is required for induction of Neural markers by bmp inhibition evidence for homeogenetic induction and implications for xenopus animal cap and chick explant assays
Developmental Biology, 2009Co-Authors: Claudia Linker, Costis Papanayotou, Irene De Almeida, Andrea Streit, Matthew J Stower, Virginie Sabado, Ehsan Ghorani, Roberto Mayor, Claudio D SternAbstract:In Xenopus, the animal cap is very sensitive to BMP antagonists, which result in Neuralization. In chick, however, only cells at the border of the Neural Plate can be Neuralized by BMP inhibition. Here we compare the two systems. BMP antagonists can induce Neural Plate border markers in both ventral Xenopus epidermis and non-Neural chick epiblast. However, BMP antagonism can only Neuralize ectodermal cells when the BMP-inhibited cells form a continuous trail connecting them to the Neural Plate or its border, suggesting that homeogenetic Neuralizing factors can only travel between BMP-inhibited cells. Xenopus animal cap explants contain cells fated to contribute to the Neural Plate border and even to the anterior Neural Plate, explaining why they are so easily Neuralized by BMP-inhibition. Furthermore, chick explants isolated from embryonic epiblast behave like Xenopus animal caps and express border markers. We propose that the animal cap assay in Xenopus and explant assays in the chick are unsuitable for studying instructive signals in Neural induction.
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dlx5 positions the Neural crest and preplacode region at the border of the Neural Plate
Developmental Biology, 2003Co-Authors: Keith W Mclarren, Anna Litsiou, Andrea StreitAbstract:The Neural crest and sensory placodes arise from a region of the embryonic ectoderm that lies between the Neural Plate and future epidermis. While some of the signalling pathways that are involved in cell fate determination at the border of the Neural Plate have been characterised, it is still unclear how different signals are integrated. Transcription factors of the DLX gene family that may mediate such cell fate decisions are expressed at the border of the Neural Plate. Here, we demonstrate that DLX5 is involved in positioning this border by repressing Neural properties and simultaneously by promoting the formation of border-like cells that express the Neural fold markers MSX1 and BMP4 and the preplacodal region marker SIX4. However, DLX5 is not sufficient to impart epidermal character or to specify cell fates that arise at the border of the Neural Plate, like Neural crest or fully formed sensory placodes, in a cell-autonomous manner. Additional signals are generated when mature Neural Plate and epidermis interact and these are required for Neural crest formation. We propose that patterning of the embryonic ectoderm is a multistep process that sequentially subdivides the ectoderm into regions with defined cell fates.
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establishment and maintenance of the border of the Neural Plate in the chick involvement of fgf and bmp activity
Mechanisms of Development, 1999Co-Authors: Andrea Streit, Claudio D SternAbstract:We have investigated the cell interactions and signalling molecules involved in setting up and maintaining the border between the Neural Plate and the adjacent non-Neural ectoderm in the chick embryo at primitive streak stages. msx-1, a target of BMP signalling, is expressed in this border at a very early stage. It is induced by FGF and by signals from the organizer, Hensen's node. The node also induces a ring of BMP-4, some distance away. By the early neurula stage, the edge of the Neural Plate is the only major site of BMP-4 and msx-1 expression, and is also the only site that responds to BMP inhibition or overexpression. At this time, the Neural Plate appears to have a low level of BMP antagonist activity. Using in vivo grafts and in vitro assays, we show that the position of the border is further maintained by interactions between non-Neural and Neural ectoderm. We conclude that the border develops by integration of signals from the organizer, the developing Neural Plate, the paraxial mesoderm and the non-Neural epiblast, involving FGFs, BMPs and their inhibitors. We suggest that BMPs act in an autocrine way to maintain the border state.