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

Sean J. Morrison, Sharon E. Perez, Zhou Qiao, Joseph M. Verdi, Carol Hicks, Gerry Weinmaster, David J. Anderson

Research output: Contribution to journalArticle

541 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)499-510
Number of pages12
JournalCell
Volume101
Issue number5
DOIs
StatePublished - May 26 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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