Essential roles of mesenchyme-derived beta-catenin in mouse Mullerian duct morphogenesis
Essential roles of mesenchyme-derived beta-catenin in mouse Mullerian duct morphogenesis
复制标题
DOI：
10.1016/j.ydbio.2007.04.036
复制
发表时间：
2007-07-15
影响因子：
2.7
通讯作者：
Yao, Humphrey Hung-Chang
中科院分区：
文献类型：
--
作者：
Deutseher, Erica;Yao, Humphrey Hung-Chang
Wnt家族成员如Wnt4、Wnt5a和Wnt7a与女性生殖道不同部位的苗勒管的形成和形态发生有关。这些WNT配体通过典型的WNT/β-连环蛋白或非典型的WNT/钙途径发挥作用，并可能在米勒管分化中发挥冗余作用。通过使用苗勒管特异的抗苗勒氏激素受体2受体ERE(Amhr2-cre)小鼠系，我们建立了一种条件性基因敲除模型，该模型可以特异性地去除苗勒管间质中的β-连环素。出生时，苗勒管间充质中β-连环素的丢失扰乱了敲除胚胎中输卵管的正常卷曲，类似于Wnt7a基因敲除的表型。女性生殖道的整体发育在出生时就受到阻碍，间充质和上皮细胞的增殖减少。我们还发现Wnt5a和Wnt7a的表达保持正常，排除了Wnt5a和Wnt7a的表型可能是这些Wnt配体丢失的可能性。我们检测了WNT的受体FrizzledFzd的表达，发现Fzd1是存在于苗勒管间充质中的一种受体，可能是米勒管中β-连环素激活的受体。综上所述，我们的发现表明，间充质β-连环蛋白是WNT7a的下游效应器，它介导输卵管的模式形成和子宫的正确分化。由爱思唯尔公司出版。
Members of the Wnt family of genes such as Wnt4, Wnt5a, and Wnt7a have been implicated in the formation and morphogenesis of the Mullerian duct into various parts of the female reproductive tract. These WNT ligands elicit their action via either the canonical WNT/beta-catenin or the non-canonical WNT/calcium pathway and could possibly function redundantly in Mullerian duct differentiation. By using the Mullerian duct-specific anti-Mullerian hormone receptor 2 ere (Amhr2-cre) mouse line, we established a conditional knockout model that removed beta-catenin specifically in the mesenchyme of the Mullerian duct. At birth, loss of beta-catenin in the Mullerian duct mesenchyme disrupted the normal coiling of the oviduct in the knockout embryo, resembling the phenotype of the Wnt7a knockout. The overall development of the female reproductive tract was stunted at birth with a decrease in proliferation in the mesenchyme and epithelium. We also discovered that Wnt5a and Wnt7a expression remained normal, excluding the possibility that the phenotypes resulted from a loss of these WNT ligands. We examined the expression of Frizzled (Fzd), the receptors for WNT, and found that Fzd1 is one receptor present in the Mullerian duct mesenchyme and could be the putative receptor for beta-catenin activation in the Mullerian duct. In summary, our findings suggest that mesenchymal beta-catenin is a downstream effector of Wnt7a that mediates the patterning of the oviduct and proper differentiation of the uterus. Published by Elsevier Inc.