Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling
Sprouty2 and Sprouty4 are essential for embryonic morphogenesis and regulation of FGF signaling
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DOI：
10.1016/j.bbrc.2006.11.107
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发表时间：
2007-01-26
影响因子：
3.1
通讯作者：
Yoshimura, Akihiko
中科院分区：
文献类型：
--
作者：
Taniguchi, Koji;Ayada, Toranoshin;Yoshimura, Akihiko
发芽基因编码细胞质膜相关蛋白，抑制受体酪氨酸激酶信号。在哺乳动物中已经鉴定出四种果蝇Sprouty（dSpry）的直系同源物（Sprouty 1 -4）。Sprouty 1和Sprouty 2的生理功能已经使用基因靶向方法进行了研究，然而迄今为止尚未报道Sprouty 4敲除（KO）小鼠的详细检查。在本研究中，产生并表征Sprouty 4 KO小鼠。尽管Sprouty 4 KO小鼠中有相当一部分在出生后不久就因下颌骨缺陷而死亡，但其余小鼠仍能存活并具有生育能力。在大多数Sprouty 4缺陷小鼠中观察到生长迟缓，几乎所有Sprouty 4 KO小鼠都具有多并指畸形。ERK激活在Sprouty 4 KO小鼠胚胎成纤维细胞（MEFs）中持续响应FGF，但不响应EGF。Sproiay 2和Sprouty 4双KO（DKO）小鼠是胚胎致死的，并且在颅面、肢体和肺形态发生中显示出严重缺陷。这些发现表明Sprouty 2和Sprouty 4在胚胎发育和FGF信号传导中具有冗余和非冗余功能。(c)2006年爱思唯尔公司All rights reserved.
Sprouty genes encode cytoplasmic membrane-associated proteins that inhibit receptor tyrosine kinase signaling. Four orthologs of Drosophila Sprouty (dSpry) (Sprouty1-4) have been identified in mammals. Physiological function of Sprouty1 and Sprouty2 has been investigated using gene targeting approaches, however to date detailed examination of Sprouty4 knockout (KO) mice has not been reported. In this study, Sprouty4 KO mice were generated and characterized. Although a significant fraction of Sprouty4 KO mice died shortly after birth due to mandible defects, the remainder were viable and fertile. Growth retardation was observed for most Sprouty4-deficient mice, with nearly all Sprouty4 KO mice having polysyndactyly. ERK activation was sustained in Sprouty4 KO mouse embryonic fibroblasts (MEFs) in response to FGF, but not to EGF. Sproiay2 and Sprouty4 double KO (DKO) mice were embryonic lethal and showed severe defects in craniofacial, limb, and lung morphogenesis. These findings suggest both redundant and non-redundant functions for Sprouty2 and Sprouty4 on embryonic development and FGF signaling. (c) 2006 Elsevier Inc. All rights reserved.