期刊
STEM CELLS
卷 28, 期 9, 页码 1660-1672出版社
WILEY
DOI: 10.1002/stem.488
关键词
MAPK; Neural stem cells; Neural progenitor cells; Signal transduction; Self renewal; FRS2; SNT1; Grb2; Shp2
资金
- Ministry of Education, Science, Sports, and Culture of Japan
- Naito Foundation
- Saibo-Kagaku Foundation
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 2 alpha (FRS2 alpha), a central mediator for FGF signaling, combined with FRS2 alpha 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 FRS2 alpha 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, FRS2 alpha fine-tunes the FGF-signaling to control qualitatively different biological activities, self-renewal at least partly through Hes1 versus proliferation of NSPCs. STEM CELLS 2010;28:1660-1672
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