Department of Developmental Biology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Dev Dyn. 2010 Jun;239(6):1768-78. doi: 10.1002/dvdy.22282.
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.
Fgf 信号在小鼠原肠胚形成和左右轴形成中发挥关键作用。然而，尽管遗传分析已经揭示了 Fgf 信号在这些过程中的重要方面，但遗传研究的时间分辨率较低。在这里，我们将整个胚胎培养与应用化学化合物相结合，在特定时间点抑制 Fgf 信号。我们发现，氯酸钠和 PD173074 是早期小鼠胚胎中 Fgf 信号的有效抑制剂。Fgf 信号在原肠胚形成开始前的原始条纹的上皮到间质的转变中是必需的。一旦原肠胚形成开始，Fgf 信号通过 Ras/MAPK 下游级联来指定中胚层命运。最后，在原肠胚形成过程中，胚胎的后侧面的 Fgf 信号通过 Tbx6-Dll1 诱导节点中的 Nodal 表达，这是在左侧侧板中胚层中表达 Nodal 所需的初始事件。
