The Experts below are selected from a list of 10752 Experts worldwide ranked by ideXlab platform
Sebastien Darras - One of the best experts on this subject based on the ideXlab platform.
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the bmp chordin antagonism controls sensory pigment cell specification and differentiation in the ascidian embryo
Developmental Biology, 2001Co-Authors: Sebastien Darras, Hiroki NishidaAbstract:We have investigated the role of the bone morphogenetic protein (BMP) pathway during Neural tissue formation in the ascidian embryo. The orthologue of the BMP antagonist, chordin, was isolated from the ascidian Halocynthia roretzi. While both the expression pattern and the phenotype observed by overexpressing chordin or BMPb (the dpp-subclass BMP) do not suggest a role for these factors in Neural induction, BMP/CHORDIN antagonism was found to affect Neural Patterning. Overexpression of BMPb induced ectopic sensory pigment cells in the brain lineages that do not normally form pigment cells and suppressed pressure organ formation within the brain. Reciprocally, overexpressing chordin suppressed pigment cell formation and induced ectopic pressure organ. We show that pigment cell formation occurs in three steps. (1) During cleavage stages ectodermal cells are Neuralized by a vegetal signal that can be substituted by bFGF. (2) At the early gastrula stage, BMPb secreted from the lateral nerve cord blastomeres induces those Neuralized blastomeres in close proximity to adopt a pigment cell fate. (3) At the tailbud stage, among these pigment cell precursors, BMPb induces the differentiation of specifically the anterior type of pigment cell, the otolith; while posteriorly, CHORDIN suppresses BMP activity and allows ocellus differentiation.
Thomas M Jessell - One of the best experts on this subject based on the ideXlab platform.
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a requirement for retinoic acid mediated transcriptional activation in ventral Neural Patterning and motor neuron specification
Neuron, 2003Co-Authors: Bennett G Novitch, Hynek Wichterle, Thomas M Jessell, Shanthini SockanathanAbstract:Abstract The specification of neuronal fates in the ventral spinal cord depends on the regulation of homeodomain (HD) and basic-helix-loop-helix (bHLH) proteins by Sonic hedgehog (Shh). Most of these transcription factors function as repressors, leaving unresolved the link between inductive signaling pathways and transcriptional activators involved in ventral neuronal specification. We show here that retinoid signaling and the activator functions of retinoid receptors are required to pattern the expression of HD and bHLH proteins and to specify motor neuron identity. We also show that fibroblast growth factors (FGFs) repress progenitor HD protein expression, implying that evasion of FGF signaling and exposure to retinoid and Shh signals are obligate steps in the emergence of ventral Neural pattern. Moreover, joint exposure of Neural progenitors to retinoids and FGFs suffices to induce motor neuron differentiation in a Shh-independent manner.
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groucho mediated transcriptional repression establishes progenitor cell pattern and neuronal fate in the ventral Neural tube
Cell, 2001Co-Authors: Jonas Muhr, Thomas M Jessell, Elisabet Andersson, Madelen Persson, Johan EricsonAbstract:Abstract The pattern of neuronal specification in the ventral Neural tube is controlled by homeodomain transcription factors expressed by Neural progenitor cells, but no general logic has emerged to explain how these proteins determine neuronal fate. We show that most of these homeodomain proteins possess a conserved eh1 motif that mediates the recruitment of Gro/TLE corepressors. The eh1 motif underlies the function of these proteins as repressors during Neural Patterning in vivo. Inhibition of Gro/TLE-mediated repression in vivo results in a deregulation of cell pattern in the Neural tube. These results imply that the pattern of neurogenesis in the Neural tube is achieved through the spatially controlled repression of transcriptional repressors—a derepression strategy of neuronal fate specification.
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regulation of the Neural Patterning activity of sonic hedgehog by secreted bmp inhibitors expressed by notochord and somites
Development, 2000Co-Authors: Karel F Liem, Thomas M Jessell, James BriscoeAbstract:The secretion of Sonic hedgehog (Shh) from the notochord and floor plate appears to generate a ventral-to-dorsal gradient of Shh activity that directs progenitor cell identity and neuronal fate in the ventral Neural tube. In principle, the establishment of this Shh activity gradient could be achieved through the graded distribution of the Shh protein itself, or could depend on additional cell surface or secreted proteins that modify the response of Neural cells to Shh. Cells of the Neural plate differentiate from a region of the ectoderm that has recently expressed high levels of BMPs, raising the possibility that prospective ventral Neural cells are exposed to residual levels of BMP activity. We have examined whether modulation of the level of BMP signaling regulates Neural cell responses to Shh, and thus might contribute to the Patterning of cell types in the ventral Neural tube. Using an in vitro assay of Neural cell differentiation we show that BMP signaling markedly alters Neural cell responses to Shh signals, eliciting a ventral-to-dorsal switch in progenitor cell identity and neuronal fate. BMP signaling is regulated by secreted inhibitory factors, including noggin and follistatin, both of which are expressed in or adjacent to the Neural plate. Conversely, follistatin but not noggin produces a dorsal-toventral switch in progenitor cell identity and neuronal fate in response to Shh both in vitro and in vivo. These results suggest that the specification of ventral Neural cell types depends on the integration of Shh and BMP signaling activities. The net level of BMP signaling within Neural tissue may be regulated by follistatin and perhaps other BMP inhibitors secreted by mesodermal cell types that flank the ventral Neural tube. SUMMARY
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ventral Neural Patterning by nkx homeobox genes nkx6 1 controls somatic motor neuron and ventral interneuron fates
Genes & Development, 2000Co-Authors: Maike Sander, Thomas M Jessell, Johan Ericson, Sussan Paydar, James Briscoe, Elizabeth Berber, Michael S German, John L R RubensteinAbstract:There is growing evidence that sonic hedgehog (Shh) signaling regulates ventral neuronal fate in the vertebrate central nervous system through Nkx-class homeodomain proteins. We have examined the patterns of neurogenesis in mice carrying a targeted mutation in Nkx6.1. These mutants show a dorsal-to-ventral switch in the identity of progenitors and in the fate of postmitotic neurons. At many axial levels there is a complete block in the generation of V2 interneurons and motor neurons and a compensatory ventral expansion in the domain of generation of V1 neurons, demonstrating the essential functions of Nkx6.1 in regional Patterning and neuronal fate determination.
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genetic ablation reveals that the roof plate is essential for dorsal interneuron specification
Nature, 2000Co-Authors: Paula Dietrich, Thomas M JessellAbstract:During Neural development in vertebrates, a spatially ordered array of neurons is generated in response to inductive signals derived from localized organizing centres. One organizing centre that has been proposed to have a role in the control of Neural Patterning is the roof plate. To define the contribution of signals derived from the roof plate to the specification of neuronal cell types in the dorsal Neural tube, we devised a genetic strategy to ablate the roof plate selectively in mouse embryos. Embryos without a roof plate lack all the interneuron subtypes that are normally generated in the dorsal third of the Neural tube. Using a genetically based lineage analysis and in vitro assays, we show that the loss of these neurons results from the elimination of non-autonomous signals provided by the roof plate. These results reveal that the roof plate is essential for specifying multiple classes of neurons in the mammalian central nervous system.
Hiroki Nishida - One of the best experts on this subject based on the ideXlab platform.
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the bmp chordin antagonism controls sensory pigment cell specification and differentiation in the ascidian embryo
Developmental Biology, 2001Co-Authors: Sebastien Darras, Hiroki NishidaAbstract:We have investigated the role of the bone morphogenetic protein (BMP) pathway during Neural tissue formation in the ascidian embryo. The orthologue of the BMP antagonist, chordin, was isolated from the ascidian Halocynthia roretzi. While both the expression pattern and the phenotype observed by overexpressing chordin or BMPb (the dpp-subclass BMP) do not suggest a role for these factors in Neural induction, BMP/CHORDIN antagonism was found to affect Neural Patterning. Overexpression of BMPb induced ectopic sensory pigment cells in the brain lineages that do not normally form pigment cells and suppressed pressure organ formation within the brain. Reciprocally, overexpressing chordin suppressed pigment cell formation and induced ectopic pressure organ. We show that pigment cell formation occurs in three steps. (1) During cleavage stages ectodermal cells are Neuralized by a vegetal signal that can be substituted by bFGF. (2) At the early gastrula stage, BMPb secreted from the lateral nerve cord blastomeres induces those Neuralized blastomeres in close proximity to adopt a pigment cell fate. (3) At the tailbud stage, among these pigment cell precursors, BMPb induces the differentiation of specifically the anterior type of pigment cell, the otolith; while posteriorly, CHORDIN suppresses BMP activity and allows ocellus differentiation.
Christof Niehrs - One of the best experts on this subject based on the ideXlab platform.
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a morphogen gradient of wnt β catenin signalling regulates anteroposterior Neural Patterning in xenopus
Development, 2001Co-Authors: Clemens Kiecker, Christof NiehrsAbstract:Anteroposterior (AP) Patterning of the vertebrate Neural plate is initiated during gastrulation and is regulated by Spemann’s organizer and its derivatives. The prevailing model for AP Patterning predicts a caudally increasing gradient of a ‘transformer’ which posteriorizes anteriorly specified Neural cells. However, the molecular identity of the transforming gradient has remained elusive. We show that in Xenopus embryos (1) dose-dependent Wnt signalling is both necessary and sufficient for AP Patterning of the neuraxis, (2) Wnt/β-catenin signalling occurs in a direct and long-range fashion within the ectoderm, and (3) that there is an endogenous AP gradient of Wnt/β-catenin signalling in the presumptive Neural plate of the Xenopus gastrula. Our results indicate that an activity gradient of Wnt/β-catenin signalling acts as transforming morphogen to pattern the Xenopus central nervous system.
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the role of xenopus dickkopf1 in prechordal plate specification and Neural Patterning
Development, 2000Co-Authors: Olga Kazanskaya, Andrey Glinka, Christof NiehrsAbstract:Dickkopf1 (dkk1) encodes a secreted WNT inhibitor expressed in Spemann's organizer, which has been implicated in head induction in Xenopus. Here we have analyzed the role of dkk1 in endomesoderm specification and Neural Patterning by gain- and loss-of-function approaches. We find that dkk1, unlike other WNT inhibitors, is able to induce functional prechordal plate, which explains its ability to induce secondary heads with bilateral eyes. This may be due to differential WNT inhibition since dkk1, unlike frzb, inhibits Wnt3a signalling. Injection of inhibitory antiDkk1 antibodies reveals that dkk1 is not only sufficient but also required for prechordal plate formation but not for notochord formation. In the Neural plate dkk1 is required for anteroposterior and dorsoventral Patterning between mes- and telencephalon, where dkk1 promotes anterior and ventral fates. Both the requirement of anterior explants for dkk1 function and their ability to respond to dkk1 terminate at late gastrula stage. Xenopus embryos posteriorized with bFGF, BMP4 and Smads are rescued by dkk1. dkk1 does not interfere with the ability of bFGF to induce its immediate early target gene Xbra, indicating that its effect is indirect. In contrast, there is cross-talk between BMP and WNT signalling, since induction of BMP target genes is sensitive to WNT inhibitors until the early gastrula stage. Embryos treated with retinoic acid (RA) are not rescued by dkk1 and RA affects the central nervous system (CNS) more posterior than dkk1, suggesting that WNTs and retinoids may act to pattern anterior and posterior CNS, respectively, during gastrulation.
Giuseppe Lupo - One of the best experts on this subject based on the ideXlab platform.
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multiple roles of activin nodal bone morphogenetic protein fibroblast growth factor and wnt β catenin signalling in the anterior Neural Patterning of adherent human embryonic stem cell cultures
Open Biology, 2013Co-Authors: Giuseppe Lupo, Claire Novorol, Joseph R Smith, Ludovic Vallier, Elena Miranda, Morgan Alexander, Stefano Biagioni, Roger A Pedersen, William A HarrisAbstract:Several studies have successfully produced a variety of Neural cell types from human embryonic stem cells (hESCs), but there has been limited systematic analysis of how different regional identities are established using well-defined differentiation conditions. We have used adherent, chemically defined cultures to analyse the roles of Activin/Nodal, bone morphogenetic protein (BMP), fibroblast growth factor (FGF) and Wnt/β-catenin signalling in Neural induction, anteroposterior Patterning and eye field specification in hESCs. We show that either BMP inhibition or activation of FGF signalling is required for effective Neural induction, but these two pathways have distinct outcomes on rostrocaudal Patterning. While BMP inhibition leads to specification of forebrain/midbrain positional identities, FGF-dependent Neural induction is associated with strong posteriorization towards hindbrain/spinal cord fates. We also demonstrate that Wnt/β-catenin signalling is activated during Neural induction and promotes acquisition of Neural fates posterior to forebrain. Therefore, inhibition of this pathway is needed for efficient forebrain specification. Finally, we provide evidence that the levels of Activin/Nodal and BMP signalling have a marked influence on further forebrain Patterning and that constitutive inhibition of these pathways represses expression of eye field genes. These results show that the key mechanisms controlling Neural Patterning in model vertebrate species are preserved in adherent, chemically defined hESC cultures and reveal new insights into the signals regulating eye field specification.