Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Dev Cell. 2011 May 17;20(5):689-99. doi: 10.1016/j.devcel.2011.04.010.
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 proapoptotic TGF-β 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.
越来越多的证据表明，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，在胚胎的头部，FGF 信号的缺失会导致形成前脑的前体细胞（包括端脑）迅速死亡。在这里，我们概述了一个调节胚胎鼠头部存活的核心遗传回路：β-catenin 介导的 WNT 信号直接维持 FGF 的表达，并且需要 FGF 在体内发挥功能，以对抗通过 SMAD4 发挥作用的促凋亡 TGF-β信号。此外，这些拮抗途径集中在凋亡的转录调控上，以及 Cdkn1a 等基因上，这表明了胚胎头部信号中心调节细胞存活的机制。
