FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak
FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak
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DOI：
10.1016/s1534-5807(01)00017-x
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发表时间：
2001-07-01
影响因子：
11.8
通讯作者：
Rossant, J
中科院分区：
文献类型：
--
作者：
Ciruna, B;Rossant, J
尽管 FGF 信号传导在原肠胚形成时中胚层的迁移和模式形成中发挥着不可或缺的作用，但 FGF 活性的机制和下游靶标仍然难以捉摸。在这里，我们证明 FGFR1 通过控制 Snail 和 E-钙粘蛋白的表达来协调原条处的上皮到间质的转变和中胚层的形态发生。此外，我们发现 FGFR1 通过正向调节 Brachyury 和 Tbx6 的表达在中胚层细胞命运规范中发挥作用。最后，我们提供的证据表明，在 Fgfr1 -/- 胚胎中观察到的 Wnt3a 信号减弱可以通过降低 E-钙粘蛋白水平来挽救。我们认为，细胞质 β-连环蛋白水平的调节与 FGF 诱导的 E-钙粘蛋白下调相关，提供了条纹处 FGF 和 Wnt 信号通路之间的分子联系。
Although FGF signaling plays an integral role in the migration and patterning of mesoderm at gastrulation, the mechanism and downstream targets of FGF activity have remained elusive. Here, we demonstrate that FGFR1 orchestrates the epithelial to mesenchymal transition and morphogenesis of mesoderm at the primitive streak by controlling Snail and E-cadherin expression. Furthermore, we show that FGFR1 functions in mesoderm cell fate specification by positively regulating Brachyury and Tbx6 expression. Finally, we provide evidence that the attenuation of Wnt3a signaling observed in Fgfr1 -/- embryos can be rescued by lowering E-cadherin levels. We propose that modulation of cytoplasmic beta-catenin levels, associated with FGF-induced downregulation of E-cadherin, provides a molecular link between FGF and Wnt signaling pathways at the streak.