Notch signaling inhibits muscle cell differentiation through a CBF1-independent pathway

Carrie Shawber, Donna Nofziger, James J.D. Hsieh, Claire Lindsell, Oliver Bögler, Diane Hayward, Gerry Weinmaster

Research output: Contribution to journalArticlepeer-review

314 Scopus citations

Abstract

Notch controls cell fate by inhibiting cellular differentiation, presumably through activation of the transcriptional regulator human C promoter Binding Factor (CBF1), which transactivates the hairy and Enhancer of split (HES-1) gene. However, we describe constitutively active forms of Notch1, which inhibit muscle cell differentiation but do not interact with CBF1 or upregulate endogenous HES-1 expression. In addition, Jagged-Notch interactions that prevent the expression of muscle cell specific genes do not involve the upregulation of endogenous HES-1. In fact, exogenous expression of HES-1 in C2C12 myoblasts does not block myogenesis. Our data demonstrate the existence of a CBF1-independent pathway by which Notch inhibits differentiation. We therefore propose that Notch signaling activates at least two different pathways: one which involves CBF1 as an intermediate and one which does not.

Original languageEnglish
Pages (from-to)3765-3773
Number of pages9
JournalDevelopment
Volume122
Issue number12
StatePublished - 1996

Keywords

  • CBF1
  • HES-1
  • Mouse
  • Muscle cell differentiation
  • Myoblast
  • Notch

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