Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression
Wt1 directs the lineage specification of sertoli and granulosa cells by repressing Sf1 expression
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Wt1 通过抑制 Sf1 表达来指导支持细胞和颗粒细胞的谱系规范
DOI：
10.1242/dev.144105
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发表时间：
2017-01-01
期刊：
影响因子：
4.6
通讯作者：
Gao, Fei
中科院分区：
文献类型：
--
作者：
Chen, Min;Zhang, Lianjun;Gao, Fei
支持细胞（Sertoli细胞和颗粒细胞）和类固醇生成细胞（Leydig细胞和卵泡膜细胞）是哺乳动物性腺中两种主要的体细胞类型，但在性腺发育过程中控制它们分化的机制仍然是未知的。在这项研究中，我们发现，性别决定后，卵巢中的Wt1基因的缺失导致类固醇生成细胞在胚胎阶段的异位发育。此外，支持细胞和颗粒细胞的分化被阻止时，Wt1删除性别决定和大多数生殖嵴体细胞分化成类固醇生成细胞在男性和女性性腺。进一步的研究表明，WT1抑制Sf1的表达，直接结合到Sf1启动子区域，和抑制功能完全废除时，WT1结合位点突变。这项研究表明，Wt1是所需的支持细胞和颗粒细胞的谱系规范抑制Sf1的表达。没有Wt1，Sf1的表达上调，体细胞分化成类固醇生成细胞，而不是支持细胞。我们的研究揭示了性腺发育过程中体细胞分化的新机制。突出显示的文章：生殖嵴体细胞具有分化为支持细胞或类固醇生成细胞的潜能，这取决于Wt1基因的表达。
Supporting cells (Sertoli and granulosa) and steroidogenic cells (Leydig and theca-interstitium) are two major somatic cell types in mammalian gonads, but the mechanisms that control their differentiation during gonad development remain elusive. In this study, we found that deletion of Wt1 in the ovary after sex determination caused ectopic development of steroidogenic cells at the embryonic stage. Furthermore, differentiation of both Sertoli and granulosa cells was blocked when Wt1 was deleted before sex determination and most genital ridge somatic cells differentiated into steroidogenic cells in both male and female gonads. Further studies revealed that WT1 repressed Sf1 expression by directly binding to the Sf1 promoter region, and the repressive function was completely abolished when WT1 binding sites were mutated. This study demonstrates that Wt1 is required for the lineage specification of both Sertoli and granulosa cells by repressing Sf1 expression. Without Wt1, the expression of Sf1 was upregulated and the somatic cells differentiated into steroidogenic cells instead of supporting cells. Our study uncovers a novel mechanism of somatic cell differentiation during gonad development. Highlighted article: Genital ridge somatic cells have the potential to differentiate into supporting cells or steroidogenic cells depending on Wt1 gene expression.