FGF signaling regulates development by processes beyond canonical pathways.

Ayan T Ray, Pierre Mazot, J Richard Brewer, Catarina Catela, Colin J Dinsmore, Philippe Soriano

Genes & development 2020 Dec 01

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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. © 2020 Ray et al.; Published by Cold Spring Harbor Laboratory Press.

Citation

Ayan T Ray, Pierre Mazot, J Richard Brewer, Catarina Catela, Colin J Dinsmore, Philippe Soriano. FGF signaling regulates development by processes beyond canonical pathways. Genes & development. 2020 Dec 01;34(23-24):1735-1752