The presence of FGF2 signaling determines whether β-catenin exerts effects on proliferation or neuronal differentiation of neural stem cells

Nipan Israsena, Min Hu, Weimin Fu, Lixin Kan, John A. Kessler*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

195 Scopus citations

Abstract

Neural stem cells proliferate and maintain multipotency when cultured in the presence of FGF2, but subsequent lineage commitment by the cells is nevertheless influenced by the exposure to FGF2. Here we show that FGF2 effects on neural stem cells are mediated, in part, by β-catenin. Conversely, the effects of β-catenin in neural stem cells depend in part upon whether there is concurrent fibroblast growth factor (FGF) signaling. FGF2 increases β-catenin signaling through several different mechanisms including increased expression of β-catenin mRNA, increased nuclear translocation of β-catenin, increased phosphorylation of GSK-3β, and tyrosine phosphorylation of β-catenin. Overexpression of β-catenin in the presence of FGF2 helps to maintain neural progenitor cells in a proliferative state. However, overexpression of β-catenin in the absence of FGF2 enhances neuronal differentiation. Further, chromatin immunoprecipitation (ChIP) assays demonstrate that both β-catenin and Lef1 bind directly to the neurogenin promoter, and luciferase reporter assays demonstrate that β-catenin is directly involved in the regulation of neurogenin 1 and possibly other proneural genes when neural stem cells are cultured in the presence of FGF2. We suggest that the balance between the mitogenic effects and the proneural effects of β-catenin is determined by the presence of FGF signaling.

Original languageEnglish (US)
Pages (from-to)220-231
Number of pages12
JournalDevelopmental Biology
Volume268
Issue number1
DOIs
StatePublished - Apr 1 2004

Keywords

  • FGF2 signaling
  • Neuronal differentiation
  • β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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