β-Catenin-dependent FGF signaling sustains cell survival in the anterior embryonic head by countering Smad4.

β-Catenin-dependent FGF signaling sustains cell survival in the anterior embryonic head by countering Smad4.
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DOI:
10.1016/j.devcel.2011.04.010
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发表时间:
2011-05-17
期刊:
影响因子:
11.8
通讯作者:
Hebert, Jean M.
Hebert, Jean M.
中科院分区:
生物学1区
文献类型:
--
作者:
Paek, Hunki;Hwang, Jee-Yeon;Zukin, R. Suzanne;Hebert, Jean M.

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越来越多的证据表明,从胚胎信号中心分泌的FGF是细胞存活的关键介质。然而,调节FGF依赖性细胞存活的机制仍然不清楚。例如,在胚胎的吻端,FGF信号传导的消融导致形成前头部(包括端脑)的前体细胞的快速死亡。在这里,我们概述了调节胚胎小鼠头部存活的核心遗传回路:通过β-连环蛋白的WNT信号传导直接维持FGF表达,并需要FGF在体内的功能来对抗通过SMAD 4的促凋亡TGFβ信号传导。此外,这些拮抗途径集中在细胞凋亡的转录调控和基因,如Cdkn 1a,这表明胚胎头部的信号中心如何调节细胞存活的机制。
Growing evidence suggests that FGFs secreted from embryonic signaling centers are key mediators of cell survival. However, the mechanisms regulating FGF-dependent cell survival remain obscure. At the rostral end of the embryo, for example, ablation of FGF signaling leads to the rapid death of the precursor cells that form the anterior head, including the telencephalon. Here we outline a core genetic circuit that regulates survival in the embryonic mouse head: WNT signaling through β-catenin directly maintains FGF expression and requires FGF function in vivo to oppose pro-apoptotic TGFβ signaling through SMAD4. Moreover, these antagonistic pathways converge on the transcriptional regulation of apoptosis, and genes such as Cdkn1a, suggesting a mechanism for how signaling centers in the embryonic head regulate cell survival.
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