Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells

Cell. 2000 May 26;101(5):499-510. doi: 10.1016/s0092-8674(00)80860-0.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Avian Proteins*
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation
  • Cell Line, Transformed
  • Chick Embryo
  • Fibroblasts / cytology
  • Humans
  • Immunoglobulin Fc Fragments / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins / metabolism*
  • Mice
  • Nerve Tissue Proteins*
  • Neural Crest / cytology*
  • Neuregulin-1 / metabolism
  • Neuroglia / cytology*
  • Neurons / cytology*
  • Receptors, Cell Surface / metabolism*
  • Receptors, Notch
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins
  • Signal Transduction
  • Solubility
  • Stem Cells / cytology*
  • Transforming Growth Factor beta*

Substances

  • Avian Proteins
  • BMP2 protein, human
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Immunoglobulin Fc Fragments
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NRG1 protein, Gallus gallus
  • NRG1 protein, human
  • Nerve Tissue Proteins
  • Neuregulin-1
  • Nrg1 protein, mouse
  • Receptors, Cell Surface
  • Receptors, Notch
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • delta protein
  • recombinant human bone morphogenetic protein-2