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FGF signaling regulates development by processes beyond canonical pathways
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 questio...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706708/ https://www.ncbi.nlm.nih.gov/pubmed/33184218 http://dx.doi.org/10.1101/gad.342956.120 |
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author | Ray, Ayan T. Mazot, Pierre Brewer, J. Richard Catela, Catarina Dinsmore, Colin J. Soriano, Philippe |
author_facet | Ray, Ayan T. Mazot, Pierre Brewer, J. Richard Catela, Catarina Dinsmore, Colin J. Soriano, Philippe |
author_sort | Ray, Ayan T. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7706708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77067082021-06-01 FGF signaling regulates development by processes beyond canonical pathways Ray, Ayan T. Mazot, Pierre Brewer, J. Richard Catela, Catarina Dinsmore, Colin J. Soriano, Philippe Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2020-12-01 /pmc/articles/PMC7706708/ /pubmed/33184218 http://dx.doi.org/10.1101/gad.342956.120 Text en © 2020 Ray et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ 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/. |
spellingShingle | Research Paper Ray, Ayan T. Mazot, Pierre Brewer, J. Richard Catela, Catarina Dinsmore, Colin J. Soriano, Philippe FGF signaling regulates development by processes beyond canonical pathways |
title | FGF signaling regulates development by processes beyond canonical pathways |
title_full | FGF signaling regulates development by processes beyond canonical pathways |
title_fullStr | FGF signaling regulates development by processes beyond canonical pathways |
title_full_unstemmed | FGF signaling regulates development by processes beyond canonical pathways |
title_short | FGF signaling regulates development by processes beyond canonical pathways |
title_sort | fgf signaling regulates development by processes beyond canonical pathways |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706708/ https://www.ncbi.nlm.nih.gov/pubmed/33184218 http://dx.doi.org/10.1101/gad.342956.120 |
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