FOXL2 and BMP2 Act Cooperatively to Regulate Follistatin Gene Expression during Ovarian Development
FOXL2 and BMP2 Act Cooperatively to Regulate Follistatin Gene Expression during Ovarian Development
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DOI：
10.1210/en.2010-0636
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发表时间：
2011-01-01
期刊：
影响因子：
4.8
通讯作者：
Koopman, Peter
中科院分区：
文献类型：
--
作者：
Kashimada, Kenichi;Pelosi, Emanuele;Koopman, Peter
卵泡抑素（Fst）是一种分泌型糖蛋白，在女性性别决定和卵巢早期发育中起重要作用，但Fst基因表达调控的确切机制尚不清楚。在这里，我们调查的作用，骨形态发生蛋白2（BMP 2）和叉头结构域转录因子L2（FOXL 2）在调控Fst表达在发育中的小鼠卵巢。Bmp 2和Fst的mRNA表达的时间分布相似，而FOXL 2蛋白和Fst mRNA在相同的卵巢细胞中共表达。在细胞培养模型中，FOXL 2和BMP 2均上调Fst表达。在离体小鼠胚胎性腺培养中，外源性BMP 2增加Fst表达，但这种作用被BMP拮抗剂Noggin抵消。此外，在Foxl 2-null小鼠中，Fst表达在整个胎儿卵巢发育过程中降低，Bmp 2表达也降低。我们的数据支持FOXL 2和BMP 2合作以确保Fst在发育中的卵巢中正确表达的模型。此外，Wnt 4基因敲除小鼠显示Fst表达减少，仅限于卵巢发育早期，表明WNT 4在Fst表达的启动中发挥作用，但不维持Fst表达。（内分泌学152：272-280，2011）
Follistatin is a secreted glycoprotein required for female sex determination and early ovarian development, but the precise mechanisms regulating follistatin (Fst) gene expression are not known. Here, we investigate the roles of bone morphogenetic protein 2 (BMP2) and forkhead-domain transcription factor L2 (FOXL2) in the regulation of Fst expression in the developing mouse ovary. Bmp2 and Fst showed similar temporal profiles of mRNA expression, whereas FOXL2 protein and Fst mRNA were coexpressed in the same ovarian cells. In a cell culture model, both FOXL2 and BMP2 up-regulated Fst expression. In ex vivo mouse fetal gonad culture, exogenous BMP2 increased Fst expression, but this effect was counteracted by the BMP antagonist Noggin. Moreover, in Foxl2-null mice, Fst expression was reduced throughout fetal ovarian development, and Bmp2 expression was also reduced. Our data support a model in which FOXL2 and BMP2 cooperate to ensure correct expression of Fst in the developing ovary. Further, Wnt4-knockout mice showed reduced expression of Fst limited to early ovarian development, suggesting a role for WNT4 in the initiation, but not the maintenance, of Fst expression. (Endocrinology 152: 272-280, 2011)