Fgfr1 regulates development through the combinatorial use of signaling proteins.

Genes & Development
J Richard BrewerPhilippe Soriano

Abstract

Fibroblast growth factor (Fgf) signaling governs multiple processes important in development and disease. Many lines of evidence have implicated Erk1/2 signaling induced through Frs2 as the predominant effector pathway downstream from Fgf receptors (Fgfrs), but these receptors can also signal through other mechanisms. To explore the functional significance of the full range of signaling downstream from Fgfrs in mice, we engineered an allelic series of knock-in point mutations designed to disrupt Fgfr1 signaling functions individually and in combination. Analysis of each mutant indicates that Frs2 binding to Fgfr1 has the most pleiotropic functions in development but also that the receptor uses multiple proteins additively in vivo. In addition to Frs2, Crk proteins and Plcγ also contribute to Erk1/2 activation, affecting axis elongation and craniofacial and limb development and providing a biochemical mechanism for additive signaling requirements. Disruption of all known signaling functions diminished Erk1/2 and Plcγ activation but did not recapitulate the peri-implantation Fgfr1-null phenotype. This suggests that Erk1/2-independent signaling pathways are functionally important for Fgf signaling in vivo.

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Citations

May 24, 2017·Zygote : the Biology of Gametes and Early Embryos·Peter L PfefferDebra K Berg
Nov 20, 2016·Genes & Development·Katherine A Fantauzzo, Philippe Soriano
Sep 27, 2018·Genesis : the Journal of Genetics and Development·Diana RigueurAmy E Merrill
Apr 3, 2016·Genes & Development·J Richard BrewerPhilippe Soriano
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Oct 3, 2020·Genes & Development·James F ClarkPhilippe Soriano
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Mar 2, 2017·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Bradley PawlikowskiBradley B Olwin
Feb 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Michaela Kunova BosakovaPavel Krejci
May 23, 2018·Science China. Life Sciences·Philippe Soriano
Jan 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Giuliano G StirparoJennifer Nichols
Nov 14, 2020·Genes & Development·Ayan T RayPhilippe Soriano
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Oct 23, 2020·Developmental Cell·Claire S SimonAnna-Katerina Hadjantonakis

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