Fibroblast growth factor receptor 2 regulates proliferation and Sertoli differentiation during male sex determination
Fibroblast growth factor receptor 2 regulates proliferation and Sertoli differentiation during male sex determination
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DOI：
10.1073/pnas.0702581104
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发表时间：
2007-10-16
影响因子：
11.1
通讯作者：
Capel, Blanche
中科院分区：
文献类型：
--
作者：
Kim, Yuna;Bingham, Nathan;Capel, Blanche
小鼠中Fgf9的靶向突变导致雄性到雌性的性别逆转。在四种FGF受体中，FGFR 2基于抗体染色显示出两种高度特异性的模式，这表明它可能是性腺中介导FGF9信号传导的受体。FGFR2在增殖的体腔上皮细胞的质膜和支持祖细胞的细胞核中被检测到。这种表达模式表明Fgfr 2可能在睾丸发育中发挥多个作用。为了验证Fgfr 2是男性性别决定所需的假设，我们将携带Fgfr 2 floxed等位基因的小鼠与两种不同的Cre系杂交，以诱导该受体的暂时或细胞特异性缺失。结果表明，胚胎性腺中Fgfr 2的缺失与Fgf 9的缺失表型相似，并导致雄性到雌性的性逆转。使用这两个Cre系，我们提供了第一个遗传证据，Fgfr 2在睾丸发育过程中的增殖和支持细胞分化中发挥着不同的作用。
Targeted mutagenesis of Fgf9 in mice causes male-to-female sex reversal. Among the four FGF receptors, FGFR2 showed two highly specific patterns based on antibody staining, suggesting that it might be the receptor-mediating FGF9 signaling in the gonad. FGFR2 was detected at the plasma membrane in proliferating coelomic epithelial cells and in the nucleus in Sertoli progenitor cells. This expression pattern suggested that Fgfr2 might play more than one role in testis development. To test the hypothesis that Fgfr2 is required for male sex determination, we crossed mice carrying a floxed allele of Fgfr2 with two different Cre lines to induce a temporal or cell-specific deletion of this receptor. Results show that deletion of Fgfr2 in embryonic gonads phenocopies deletion of Fgf9 and leads to male-to-female sex reversal. Using these two Cre lines, we provide the first genetic evidence that Fgfr2 plays distinct roles in proliferation and Sertoli cell differentiation during testis development.