Dissecting the Role of Fgf Signaling During Gastrulation and Left-Right Axis Formation in Mouse Embryos Using Chemical Inhibitors
Dissecting the Role of Fgf Signaling During Gastrulation and Left-Right Axis Formation in Mouse Embryos Using Chemical Inhibitors
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DOI：
10.1002/dvdy.22282
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发表时间：
2010-06-01
影响因子：
2.5
通讯作者：
Meno, Chikara
中科院分区：
文献类型：
--
作者：
Oki, Shinya;Kitajima, Keiko;Meno, Chikara
成纤维细胞生长因子信号在小鼠原肠胚形成和左右轴形成中起关键作用。然而，尽管遗传分析揭示了这些过程中FGF信号传导的重要方面，但遗传研究的时间分辨率较低。在这里，我们将全胚胎培养与化合物的应用相结合，以在特定时间点抑制FGF信号传导。我们发现氯酸钠和PD 173074是小鼠早期胚胎中FGF信号传导的有效抑制剂。Fgf信号是原肠胚形成前原条上皮细胞向间充质细胞转化所必需的。一旦原肠胚形成开始，FGF信号通过Ras/MAPK下游级联指定中胚层命运。最后，原肠胚形成期间胚胎后侧的Fgf信号传导通过Tbx 6-Dll 1诱导节点中的Nodal表达，这是左侧板中胚层中Nodal表达所需的初始事件。发展动力学239：1768-1778，2010年。(C)2010 Wiley-Liss，Inc.
Fgf signaling plays pivotal roles in mouse gastrulation and left-right axis formation. However, although genetic analyses have revealed important aspects of Fgf signaling in these processes, the temporal resolution of genetic studies is low. Here, we combined whole-embryo culture with application of chemical compounds to inhibit Fgf signaling at specific time points. We found that sodium chlorate and PD173074 are potent inhibitors of Fgf signaling in early mouse embryos. Fgf signaling is required for the epithelial-to-mesenchymal transition of the primitive streak before the onset of gastrulation. Once gastrulation begins, Fgf signaling specifies mesodermal fates via the Ras/MAPK downstream cascade. Finally, Fgf signaling on the posterior side of the embryo during gastrulation induces Nodal expression in the node via Tbx6-Dll1, the initial event required for Nodal expression in the left lateral plate mesoderm. Developmental Dynamics 239:1768-1778, 2010. (C) 2010 Wiley-Liss, Inc.