Abstract
The genesis of vertebrate peripheral ganglia poses the problem of how multipotent neural crest stem cells (NCSCs) can sequentially generate neurons and then glia in a local environment containing strong instructive neurogenic factors, such as BMP2. Here we show that Notch ligands, which are normally expressed on differentiating neuroblasts, can inhibit neurogenesis in NCSCs in a manner that is completely dominant to BMP2. Contrary to expectation, Notch activation did not maintain these stem cells in an uncommitted state or promote their self-renewal. Rather, even a transient activation of Notch was sufficient to cause a rapid and irreversible loss of neurogenic capacity accompanied by accelerated glial differentiation. These data suggest that Notch ligands expressed by neuroblasts may act positively to instruct a cell-heritable switch to gliogenesis in neighboring stem cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Avian Proteins*
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / metabolism
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Cell Differentiation
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Cell Line, Transformed
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Chick Embryo
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Fibroblasts / cytology
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Humans
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Immunoglobulin Fc Fragments / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / metabolism*
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Mice
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Nerve Tissue Proteins*
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Neural Crest / cytology*
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Neuregulin-1 / metabolism
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Neuroglia / cytology*
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Neurons / cytology*
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Receptors, Cell Surface / metabolism*
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Receptors, Notch
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins
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Signal Transduction
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Solubility
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Stem Cells / cytology*
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Transforming Growth Factor beta*
Substances
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Avian Proteins
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BMP2 protein, human
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Bmp2 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Immunoglobulin Fc Fragments
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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NRG1 protein, Gallus gallus
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NRG1 protein, human
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Nerve Tissue Proteins
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Neuregulin-1
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Nrg1 protein, mouse
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Receptors, Cell Surface
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Receptors, Notch
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Recombinant Fusion Proteins
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Recombinant Proteins
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Transforming Growth Factor beta
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delta protein
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recombinant human bone morphogenetic protein-2