title: Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells.
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.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Morrison
authors.forename: S E
authors.initials: SE
authors.lastname: Perez
authors.forename: Z
authors.initials: Z
authors.lastname: Qiao
authors.forename: J M
authors.initials: JM
authors.lastname: Verdi
authors.forename: C
authors.initials: C
authors.lastname: Hicks
authors.forename: G
authors.initials: G
authors.lastname: Weinmaster
authors.forename: D J
authors.initials: DJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D030161:Avian Proteins; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002642:Chick Embryo; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins; D009432:Neural Crest / Q000166:cytology*; D020890:Neuregulin-1 / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology*; D009474:Neurons / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction; D012995:Solubility; D013234:Stem Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta
chemical_list: D030161:Avian Proteins; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D007141:Immunoglobulin Fc Fragments; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C490582:NRG1 protein, Gallus gallus; C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C064045:delta protein; C499469:recombinant human bone morphogenetic protein-2