FGFs are key developmental regulators that engage a signal transduction cascade through receptor tyrosine kinases, prominently engaging ERK1/2 but also other pathways. However, it remains unknown whether all FGF activities depend on this canonical signal transduction cascade. To address this question, we generated allelic series of knock-in Fgfr1 and Fgfr2 mouse strains, carrying point mutations that disrupt binding of signaling effectors, and a kinase dead allele of Fgfr2 that broadly phenocopies the null mutant. When interrogated in cranial neural crest cells, we identified discrete functions for signaling pathways in specific craniofacial contexts, but point mutations, even when combined, failed to recapitulate the single or double null mutant phenotypes. Furthermore, the signaling mutations abrogated established FGF-induced signal transduction pathways, yet FGF functions such as cell–matrix and cell–cell adhesion remained unaffected, though these activities did require FGFR kinase activity. Our studies establish combinatorial roles of Fgfr1 and Fgfr2 in development and uncouple novel FGFR kinase-dependent cell adhesion properties from canonical intracellular signaling.

中文翻译：

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FGF信号传导通过超越常规途径的过程调节发育

FGF是关键的发育调节因子，可通过受体酪氨酸激酶参与信号转导级联反应，从而显着参与ERK1 / 2以及其他途径。但是，尚不清楚是否所有的FGF活动都依赖于这种规范的信号转导级联。为了解决这个问题，我们生成了敲入Fgfr1和Fgfr2小鼠品系的等位基因系列，携带破坏信号传导效应子结合的点突变，以及Fgfr2的激酶死亡等位基因大致表型化了无效突变体。当在颅神经cells细胞中进行询问时，我们确定了在特定颅面环境中信号通路的离散功能，但是点突变（即使组合在一起）也无法概括单个或双重无效突变表型。此外，信号突变消除了已建立的FGF诱导的信号转导途径，但是FGF功能（如细胞基质和细胞间粘附）仍然不受影响，尽管这些活性确实需要FGFR激酶活性。我们的研究建立了Fgfr1和Fgfr2在发育中的组合作用，并从规范的细胞内信号传导中解离了新的FGFR激酶依赖性细胞粘附特性。