The docking protein FRS2α is an essential component of multiple fibroblast growth factor responses during early mouse development
The docking protein FRS2α is an essential component of multiple fibroblast growth factor responses during early mouse development
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DOI：
10.1128/mcb.25.10.4105-4116.2005
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发表时间：
2005-05-01
影响因子：
5.3
通讯作者：
Schlessinger, J
中科院分区：
文献类型：
--
作者：
Gotoh, N;Manova, K;Schlessinger, J
对接蛋白FRS 2 α是成纤维细胞生长因子（FGF）信号传导的主要介质。然而，FRS 2 α在体内的生理作用仍然未知。在这份报告中，我们表明，Frs 2 α-null小鼠胚胎在前后（A-P）轴的形成有缺陷，发育迟缓，导致胚胎死亡的胚胎。第八天。我们证明，FRS 2 α是必不可少的自我更新的滋养层干细胞（TS）的维护响应FGF 4在胚外外胚层（ExE），产生胎盘组织。通过分析嵌合体胚胎，我们发现FRS 2 α在原肠胚形成期间通过原始条纹的细胞运动中也起作用。此外，实验表明，Bmp 4在TS细胞中的表达是由丝裂原活化蛋白激酶依赖性FGF 4刺激控制。此外，在Frs 2 α-null胚胎中，ExE中Bmp 4的表达和外胚层中Smad 1/5的激活都降低。这些实验强调了FRS 2 α在胚胎发育过程中介导多个过程的关键作用，并揭示了FGF和Bmp 4信号通路在早期胚胎发生中的潜在新联系。
The docking protein FRS2 alpha is a major mediator of fibroblast growth factor (FGF) signaling. However, the physiological role of FRS2 alpha in vivo remains unknown. In this report, we show that Frs2 alpha-null mouse embryos have a defect in anterior-posterior (A-P) axis formation and are developmentally retarded, resulting in embryonic lethality by embryonic. day 8. We demonstrate that FRS2 alpha is essential for the maintenance of self-renewing trophoblast stem (TS) cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to tissues of the placenta. By analyzing chimeric embryos, we found that FRS2 alpha also plays a role in cell movement through the primitive streak during gastrulation. In addition, experiments are presented demonstrating that Bmp4 expression in TS cells is controlled by mitogen-activated protein kinase-dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and activation of Smad1/5 in epiblasts are reduced in Frs2 alpha-null embryos. These experiments underscore the critical role of FRS2 alpha in mediating multiple processes during embryonic development and reveal a potential new link between FGF and Bmp4 signaling pathways in early embryogenesis.