Activation of β-catenin signaling by Rspo1 controls differentiation of the mammalian ovary
Activation of β-catenin signaling by Rspo1 controls differentiation of the mammalian ovary
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DOI：
10.1093/hmg/ddn016
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Chaboissier, Marie-Christine
中科院分区：
文献类型：
--
作者：
Chassot, Anne-Amandine;Ranc, Fariba;Chaboissier, Marie-Christine
一个人的性别是由性腺的命运决定的。虽然Sry和Sox 9的表达足以诱导雄性发育，但我们在这里表明，雌性分化需要激活经典的β-连环蛋白信号通路。XX性腺中β-连环蛋白激活受Rspo 1控制，Rspo 1敲除小鼠显示雄性化性腺。分子分析表明，女性特异性激活Wnt 4的情况下，作为一个结果XY样血管化和类固醇生成。此外，XX基因敲除胚胎的生殖细胞显示细胞粘附的变化和进入XX特异性减数分裂的失败。性索在出生前后发育，此时Sox 9被强烈激活。因此，Sox 9和β-连环蛋白激活之间的平衡决定了性腺的命运，Rspo 1作为女性发育所需的经典β-连环蛋白信号传导的关键调节因子。
The sex of an individual is determined by the fate of the gonad. While the expression of Sry and Sox9 is sufficient to induce male development, we here show that female differentiation requires activation of the canonical beta-catenin signaling pathway. beta-catenin activation is controlled by Rspo1 in XX gonads and Rspo1 knockout mice show masculinized gonads. Molecular analyses demonstrate an absence of female-specific activation of Wnt4 and as a consequence XY-like vascularization and steroidogenesis. Moreover, germ cells of XX knockout embryos show changes in cellular adhesions and a failure to enter XX specific meiosis. Sex cords develop around birth, when Sox9 becomes strongly activated. Thus, a balance between Sox9 and beta-catenin activation determines the fate of the gonad, with Rspo1 acting as a crucial regulator of canonical beta-catenin signaling required for female development.