Region-specific regulation of cell proliferation by FGF receptor signaling during the Wolffian duct development.
Region-specific regulation of cell proliferation by FGF receptor signaling during the Wolffian duct development.
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DOI：
10.1016/j.ydbio.2015.01.023
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发表时间：
2015-04-01
影响因子：
2.7
通讯作者：
Yamada, Gen
中科院分区：
文献类型：
--
作者：
Okazawa, Mika;Murashima, Aki;Harada, Masayo;Nakagata, Naomi;Noguchi, Masafumi;Morimoto, Mitsuru;Kimura, Tadashi;Ornitz, David M.;Yamada, Gen
沃尔夫氏管（WD）是雄性生殖道和肾集合管系统的原基。成纤维细胞生长因子受体（FGFR）是受体酪氨酸激酶（RTK）家族的成员，对肾脏发育至关重要。虽然FGFR信号传导在肾脏形态发生中的功能已经被分析，但它们在WD发展中的功能尚未被全面研究。在这里，我们证明，Fgfr 2是主要的Fgfr基因表达的整个WD上皮细胞，它是必不可少的维护WD，特别是在尾部的WD。Hoxb 7-Cre介导的Fgfr 2在小鼠WD上皮中的失活导致WD尾部的退化和异常的雄性生殖道发育。细胞增殖和RTK信号的下游靶基因（Etv 4和Etv 5）的表达减少在尾侧部分的WD上皮细胞在突变胚胎。颅（喙）WD的形成和输尿管出芽不受影响。Ret、Etv 4和Etv 5在突变胚胎的输尿管芽中持续表达。综上所述，这些数据表明在发育中的尾部WD上皮中FGFR 2信号传导的区域特异性要求。
The Wolffian duct (WD) is a primordium of the male reproductive tract and kidney collecting duct system. Fibroblast growth factor receptors (FGFRs), members of the receptor tyrosine kinase (RTK) family, are essential for kidney development. Although the functions of FGFR signaling in kidney morphogenesis have been analyzed, their function in WD development has not been comprehensively investigated. Here, we demonstrate that Fgfr2 is the major Fgfr gene expressed throughout the WD epithelia and that it is essential for the maintenance of the WD, specifically in the caudal part of the WD. Hoxb7-Cre mediated inactivation of Fgfr2 in the mouse WD epithelia resulted in the regression of the caudal part of the WD and abnormal male reproductive tract development. Cell proliferation and expression of the downstream target genes of RTK signaling (Etv4 and Etv5) were decreased in the caudal part of the WD epithelia in the mutant embryos. Cranial (rostral) WD formation and ureteric budding were not affected. Ret, Etv4, and Etv5 expression were sustained in the ureteric bud of the mutant embryos. Taken together, these data suggest region-specific requirements for FGFR2 signaling in the developing caudal WD epithelia.
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影响因子：
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通讯作者：
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