Wnt4 is required for proper male as well as female sexual development
Wnt4 is required for proper male as well as female sexual development
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DOI：
10.1016/j.ydbio.2004.08.049
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发表时间：
2004-12-15
影响因子：
2.7
通讯作者：
Swain, A
中科院分区：
文献类型：
--
作者：
Jeays-Ward, K;Dandonneau, M;Swain, A
先前与哺乳动物性发育有关的基因具有雄性或雌性特异性作用。信号分子WNT 4已被证明在女性性发育中很重要。Wnt 4的缺乏引起XX性腺的雄性化，我们先前表明WNT 4的作用是抑制内皮细胞和类固醇生成细胞迁移到发育中的卵巢。在这里，我们表明，Wnt 4也有一个功能，在男性性腺。我们发现，支持细胞分化是妥协Wnt 4突变睾丸，这种缺陷发生在下游的睾丸决定基因Sty，但上游的Sox 9和Dhh，两个早期支持细胞标记。遗传分析表明，这种表型主要是由于早期生殖嵴内的WNT 4的作用。不同标记物的分析确定了野生型和Wnt 4突变体胚胎之间发育早期生殖嵴中最显著的差异是Wnt 4-/-性腺中类固醇生成细胞的显著增加。这些结果将WNT 4鉴定为参与哺乳动物睾丸决定途径的新因子，并表明基因在雄性和雌性性腺发育中可以具有特定但不同的作用。(C)2004年爱思唯尔公司All rights reserved.
Genes previously implicated in mammalian sexual development have either a male- or female-specific role. The signaling molecule WNT4 has been shown to be important in female sexual development. Lack of Wnt4 gives rise to masculinization of the XX gonad and we showed previously that the role of WNT4 was to inhibit endothelial and steroidogenic cell migration into the developing ovary. Here we show that Wnt4 also has a function in the male gonad. We find that Sertoli cell differentiation is compromised in Wnt4 mutant testes and that this defect occurs downstream of the testis-determining gene Sty but upstream of Sox9 and Dhh, two early Sertoli cell markers. Genetic analysis shows that this phenotype is primarily due to the action of WNT4 within the early genital ridge. Analysis of different markers identifies the most striking difference in the genital ridge at early stages of its development between wild-type and Wnt4 mutant embryos to be a significant increase of steroidogenic cells in the Wnt4 -/- gonad. These results identify WNT4 as a new factor involved in the mammalian testis determination pathway and show that genes can have a specific but distinct role in both male and female gonad development. (C) 2004 Elsevier Inc. All rights reserved.