Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development
Context-specific requirements for Fgfr1 signaling through Frs2 and Frs3 during mouse development
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DOI：
10.1242/dev.02242
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发表时间：
2006-02-01
期刊：
影响因子：
4.6
通讯作者：
Soriano, P
中科院分区：
文献类型：
--
作者：
Hoch, RV;Soriano, P
成纤维细胞生长因子受体1（Fgfr 1）在胚胎发育过程中发挥多效性作用，但该受体在体内的信号传导机制尚未阐明。生物化学研究表明，Fgf受体特异性底物（Frs 2，Frs 3）是Fgfr 1信号转导至MAPK和PI 3 K通路的主要介质。为了确定Fgfr 1-Frs信号传导的发育要求，我们产生了Fgfr 1上的Frs 2/3结合位点缺失的小鼠（Fgfr 1（Delta Frs/Delta Frs））。Fgfr 1（Delta Frs/Delta Frs）胚胎在胚胎发育后期死亡，并且在神经管闭合以及尾芽和咽弓的发育中表现出缺陷。然而，突变体受体能够驱动Fgfr 1在原肠胚形成和体节发生过程中的功能，并驱动正常的MAPK对Fgf的反应。这些发现表明，Fgfr 1在不同的发育环境中使用不同的信号转导机制，并且该受体的一些基本功能是由Frs独立信号转导介导的。
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.