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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
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Development ePress online publication date 18 Jan 2006
doi: 10.1242/dev.02242
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Research article
Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development
* Author for correspondence (e-mail: psoriano{at}fhcrc.org)
Frs/
Frs) in which the Frs2/3-binding site on Fgfr1 is deleted. Fgfr1
Frs/
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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Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis
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© The Company of Biologists Ltd 2006