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

Stem Cells
Takuya SatoNoriko Gotoh

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.

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Citations

Feb 20, 2013·The Journal of Cell Biology·Zamal AhmedJohn E Ladbury
Oct 18, 2015·Journal of Pineal Research·Shangming LiuAijun Hao
May 12, 2015·The Journal of Clinical Investigation·Daniel L AbravanelLewis A Chodosh
Apr 30, 2014·Molecular Neurobiology·Honghua YuanXiaorong Zhu
May 29, 2016·Cellular and Molecular Life Sciences : CMLS·Sivadasan Bindu DhaneshJackson James
Jun 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Fraser I YoungMeng Li

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Methods Mentioned

BETA
Fluorescence Activated Cell Sorting
FACS
immunoprecipitation assay

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