Induction of WNT inhibitory factor 1 expression by Müllerian inhibiting substance/antiMullerian hormone in the Müllerian duct mesenchyme is linked to Müllerian duct regression.
Induction of WNT inhibitory factor 1 expression by Müllerian inhibiting substance/antiMullerian hormone in the Müllerian duct mesenchyme is linked to Müllerian duct regression.
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DOI：
10.1016/j.ydbio.2013.12.015
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发表时间：
2014-02-01
影响因子：
2.7
通讯作者：
Teixeira, Jose M.
中科院分区：
文献类型：
--
作者：
Park, Joo Hyun;Tanaka, Yoshihiro;Arango, Nelson A.;Zhang, Lihua;Benedict, L. Andrew;Roh, Mi In;Donahoe, Patricia K.;Teixeira, Jose M.
哺乳动物性发育过程中的一个关键事件是雄性胎儿双电位泌尿生殖脊（UGR）中苗勒管（MD）的退化，这是由分化睾丸的支持细胞中苗勒管抑制物质（MIS）的表达引起的。 MD消退中涉及的旁分泌信号传导机制尚未完全了解，特别是因为MIS受体MISR2在MD周围的间质中表达，但消退同时发生在上皮和间质中。进行微阵列分析，比较 MIS 信号转导能力和 Misr2 敲除胚胎 UGR，以确定可能对 MIS 介导的 MD 消退重要的分泌因子。在表达 Misr2 的 UGR 中观察到 Wif1（一种 WNT/β-连环蛋白信号传导抑制剂）的表达增加了 7 倍。 Wif1的整体原位杂交揭示了MD上皮周围间充质MD回归窗口期间与Misr2一致的表达空间和时间模式，这在雌性UGR和Misr2敲除的UGR中都不存在。从胚胎第 13.5 天开始，通过 Wif1 特异性 siRNA 敲低雄性 UGR 中的 Wif1 表达，导致器官培养测定中 MD 保留，并且将雌性 UGR 暴露于添加的重组人 MIS 中诱导 MD 间充质中的 Wif1 表达。 Wif1 的敲低导致 MD 间充质中 β-连环蛋白及其下游靶标 TCF1/LEF1 的表达增加，并减少细胞凋亡，导致 MD 部分或完全保留。这些结果强烈表明 MD 间充质分泌的 WIF1 在男性胎儿的 MD 消退中发挥作用。
A key event during mammalian sexual development is regression of the Müllerian ducts (MDs) in the bipotential urogenital ridges (UGRs) of fetal males, which is caused by the expression of Müllerian inhibiting substance (MIS) in the Sertoli cells of the differentiating testes. The paracrine signaling mechanisms involved in MD regression are not completely understood, particularly since the receptor for MIS, MISR2, is expressed in the mesenchyme surrounding the MD, but regression occurs in both the epithelium and mesenchyme. Microarray analysis comparing MIS signaling competent and Misr2 knockout embryonic UGRs was performed to identify secreted factors that might be important for MIS-mediated regression of the MD. A seven-fold increase in the expression of Wif1, an inhibitor of WNT/β-catenin signaling, was observed in the Misr2-expressing UGRs. Whole mount in situ hybridization of Wif1 revealed a spatial and temporal pattern of expression consistent with Misr2 during the window of MD regression in the mesenchyme surrounding the MD epithelium that was absent in both female UGRs and UGRs knocked out for Misr2. Knockdown of Wif1 expression in male UGRs by Wif1-specific siRNAs beginning on embryonic day 13.5 resulted in MD retention in an organ culture assay, and exposure of female UGRs to added recombinant human MIS induced Wif1 expression in the MD mesenchyme. Knockdown of Wif1 led to increased expression of β-catenin and its downstream targets TCF1/LEF1 in the MD mesenchyme and to decreased apoptosis, resulting in partial to complete retention of the MD. These results strongly suggest that WIF1 secretion by the MD mesenchyme plays a role in MD regression in fetal males.
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影响因子：
2.7
作者：
Guioli, Silvana;Sekido, Ryohei;Lovell-Badge, Robin
通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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