@article{d680eaca520f4991b03fe261ed8f0841,
title = "FGF signaling regulates development by processes beyond canonical pathways",
abstract = "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.",
keywords = "Cell adhesion, Craniofacial development, ERK1/2, FGF, Neural crest",
author = "Ray, {Ayan T.} and Pierre Mazot and {Richard Brewer}, J. and Catarina Catela and Dinsmore, {Colin J.} and Philippe Soriano",
note = "Funding Information: Microscopy facilities for assistance and advice. C.J.D. was supported by F32 DE026678 from National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR). This work was supported in part by the Tisch Cancer Institute at Mount Sinai (P30 CA196521 Cancer Center Support Grant, for access to Mt. Sinai cores) and by grant RO1 DE022778 from NIH/NIDCR to P.S. Funding Information: We thank Jia Li and Chantel Dixon for technical assistance; Kevin Kelley for stable tissue culture facilities; Elaine Fuchs for helpful insights into cell adhesion mechanisms; Jerry Chipuk for conversations about cell death; and our laboratory colleagues, Stu Aaronson, Rob Krauss, and Sergei Sokol for critical comments on the manuscript. We thank the New York University School of Dentistry Micro-CT Core and the Mt. Sinai Flow Cytometry and Microscopy facilities for assistance and advice. C.J.D. was supported by F32 DE026678 from National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research (NIDCR). This work was supported in part by the Tisch Cancer Institute at Mount Sinai (P30 CA196521 Cancer Center Support Grant, for access to Mt. Sinai cores) and by grant RO1 DE022778 from NIH/NIDCR to P.S. Publisher Copyright: {\textcopyright} 2020 Ray et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.",
year = "2020",
month = dec,
day = "1",
doi = "10.1101/gad.342956.120",
language = "English",
volume = "34",
pages = "1735--1752",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "23-24",
}