FRS2α regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells

Takuya Sato, Takuya Shimazaki, Hayato Naka, Shin Ichi Fukami, Yasushi Satoh, Hideyuki Okano, Lax Irit, Joseph Schlessinger, Noriko Gotoh

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Fibroblast growth factor (FGF) is among the most common growth factors used in cultures to maintain self-renewal and proliferative capabilities of a variety of stem cells, including neural stem cells (NSCs). However, the molecular mechanisms underlying the control by FGF have remained elusive. Studies on mutant mice of FGF receptor substrate 2α (FRS2α), a central mediator for FGF signaling, combined with FRS2α knockdown or gain-of-function experiments, allowed us to dissect the role of FGF signaling for the self-renewal and proliferation of NSCs and to provide novel molecular mechanisms for them. We identified Hes1 as a novel self-renewal target of FGF-signaling. Quantitatively different levels of Erk activation mediated by FRS2α may regulate self-renewal of NSCs and proliferation of neural stem/progenitor cells (NSPCs); low levels of Erk activation are sufficient for the former, however, higher levels are required for maximum activity of the latter. Thus, FRS2α fine-tunes the FGF-signaling to control qualitatively different biological activities, self-renewal at least partly through Hes1 versus proliferation of NSPCs.

Original languageEnglish
Pages (from-to)1661-1673
Number of pages13
JournalStem Cells
Volume28
Issue number9
DOIs
Publication statusPublished - 2010 Sep

Keywords

  • FRS2
  • Grb2
  • MAPK
  • Neural progenitor cells
  • Neural stem cells
  • SNT1
  • Self-renewal
  • Shp2
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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