Developmental changes in Notch1 and Numb expression mediated by local cell-cell interactions underlie progressively increasing delta sensitivity in neural crest stem cells

Chris J. Kubu, Kenji Orimoto, Sean J. Morrison, Gerry Weinmaster, David J. Anderson, Joseph M. Verdi

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Neural stem cells become progressively less neurogenic and more gliogenic with development. Here, we show that between E10.5 and E14.5, neural crest stem cells (NCSCs) become increasingly sensitive to the Notch ligand Delta-Fc, a progliogenic and anti-neurogenic signal. This transition is correlated with a 20- to 30-fold increase in the relative ratio of expression of Notch and Numb (a putative inhibitor of Notch signaling). Misexpression experiments suggest that these changes contribute causally to increased Delta sensitivity. Moreover, such changes can occur in NCSCs cultured at clonal density in the absence of other cell types. However, they require local cell-cell interactions within developing clones. Delta-Fc mimics the effect of such cell-cell interactions to increase Notch and decrease Numb expression in isolated NCSCs. Thus, Delta-mediated feedback interactions between NCSCs, coupled with positive feedback control of Notch sensitivity within individual cells, may underlie developmental changes in the ligand-sensitivity of these cells.

Original languageEnglish (US)
Pages (from-to)199-214
Number of pages16
JournalDevelopmental Biology
Volume244
Issue number1
DOIs
StatePublished - Apr 1 2002

Keywords

  • BMP
  • Delta
  • Neural stem cells
  • Neurogenesis
  • Notch
  • Numb

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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