FRS2α regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells.
FRS2α regulates Erk levels to control a self-renewal target Hes1 and proliferation of FGF-responsive neural stem/progenitor cells.
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DOI：
10.1002/stem.488
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发表时间：
2010-09
期刊：
影响因子：
5.2
通讯作者：
Gotoh, Noriko
中科院分区：
文献类型：
--
作者：
Sato, Takuya;Shimazaki, Takuya;Naka, Hayato;Fukami, Shin-Ichi;Satoh, Yasushi;Okano, Hideyuki;Lax, Irit;Schlessinger, Joseph;Gotoh, Noriko
成纤维细胞生长因子(成纤维细胞生长因子)是最常见的生长因子之一，用于维持包括神经干细胞(NSCs)在内的各种干细胞的自我更新和增殖能力。然而，支持成纤维细胞生长因子调控的分子机制仍然不清楚。通过对成纤维细胞生长因子受体底物2α(FRS2α)突变小鼠的研究，结合FRS2α敲除或功能获得实验，我们可以剖析成纤维细胞生长因子信号在神经干细胞自我更新和增殖中的作用，并为其提供新的分子机制。我们发现Hes1是一种新的成纤维细胞生长因子信号的自我更新靶点。FRS2α介导的不同数量的ERK激活水平可能调节神经干细胞的自我更新和神经干/祖细胞的增殖；低水平的ERK激活对前者是足够的，而后者需要较高的水平才能达到最大的活性。因此，FRS2α微调成纤维细胞生长因子信号，以控制不同的生物学活性，至少部分地通过Hes1对NSPC的增殖进行自我更新。干细胞，2010；28：1661-1673。
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. Stem Cells 2010; 28:1661–1673.
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影响因子：
4.6
作者：
Campos, LS;Leone, DP;ffrench-Constant, C
通讯作者：
ffrench-Constant, C
影响因子：
5.3
作者：
Maric, Dragan;Pla, Alessandra Fiorio;Barker, Jeffery L.
通讯作者：
Barker, Jeffery L.
DOI：
10.1073/pnas.0308600100
发表时间：
2004-03-02
影响因子：
11.1
作者：
Haubensak, W;Attardo, A;Huttner, WB
通讯作者：
Huttner, WB
影响因子：
11.8
作者：
Niwa, Yasutaka;Masamizu, Yoshito;Kageyama, Ryoichiro
通讯作者：
Kageyama, Ryoichiro
影响因子：
3.5
作者：
Gotoh, N;Laks, S;Schlessinger, J
通讯作者：
Schlessinger, J