期刊
DEVELOPMENT
卷 133, 期 4, 页码 663-673出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.02242
关键词
Fgfr1; Frs2; Frs3; signaling; gastrulation; neural tube; tail bud; pharyngeal arches
资金
- NICHD NIH HHS [R37 HD025326, HD 25326, HD 24875, R01 HD024875] Funding Source: Medline
- NIGMS NIH HHS [GM07270] Funding Source: Medline
Fibroblast growth factor receptor 1 (Fgfr1) plays pleiotropic roles during embryonic development, but the mechanisms by which this receptor signals in vivo have not previously been elucidated. Biochemical studies have implicated Fgf receptor-specific substrates (Frs2, Frs3) as the principal mediators of Fgfr1 signal transduction to the MAPK and PI3K pathways. To determine the developmental requirements for Fgfr1-Frs signaling, we generated mice (Fgfr1(Delta Frs/Delta Frs)) in which the Frs2/3-binding site on Fgfr1 is deleted. Fgfr1(Delta Frs/Delta Frs) embryos die during late embryogenesis, and exhibit defects in neural tube closure and in the development of the tail bud and pharyngeal arches. However, the mutant receptor is able to drive Fgfr1 functions during gastrulation and somitogenesis, and drives normal MAPK responses to Fgf. These findings indicate that Fgfr1 uses distinct signal transduction mechanisms in different developmental contexts, and that some essential functions of this receptor are mediated by Frs-independent signaling.
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