Best Diana, Sahlender Daniela A, Walther Norbert, Peden Andrew A, Adams Ian R
MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
Development. 2008 Apr;135(8):1415-25. doi: 10.1242/dev.019497. Epub 2008 Mar 5.
In mammals, the supporting cell lineage in an embryonic gonad communicates the sex-determining decision to various sexually dimorphic cell types in the developing embryo, including the germ cells. However, the molecular nature of the sex-determining signals that pass from the supporting cells to the germ cells is not well understood. We have identified a conserved transmembrane protein, Sdmg1, owing to its male-specific expression in mouse embryonic gonads. Sdmg1 is expressed in the Sertoli cells of embryonic testes from 12.5 dpc, and in granulosa cells of growing follicles in adult ovaries. In Sertoli cells, Sdmg1 is localised to endosomes, and knock-down of Sdmg1 in Sertoli cell lines causes mis-localisation of the secretory SNARE Stx2 and defects in membrane trafficking. Upregulation of Sdmg1 appears to be part of a larger programme of changes to membrane trafficking pathways in embryonic Sertoli cells, and perturbing secretion in male embryonic gonads in organ culture causes male-to-female germ cell sex reversal. These data suggest that changes that occur in the cell biology of embryonic Sertoli cells may facilitate the communication of male sex-determining decisions to the germ cells during embryonic development.
在哺乳动物中，胚胎性腺中的支持细胞谱系将性别决定信息传递给发育中胚胎的各种性别二态性细胞类型，包括生殖细胞。然而，从支持细胞传递到生殖细胞的性别决定信号的分子本质尚未得到充分了解。我们鉴定出一种保守的跨膜蛋白Sdmg1，这是由于其在小鼠胚胎性腺中具有雄性特异性表达。Sdmg1在胚胎睾丸的支持细胞中从胚胎第12.5天开始表达，并在成年卵巢中生长卵泡的颗粒细胞中表达。在支持细胞中，Sdmg1定位于内体，在支持细胞系中敲低Sdmg1会导致分泌型SNARE蛋白Stx2的定位错误以及膜运输缺陷。Sdmg1的上调似乎是胚胎支持细胞中膜运输途径更大变化程序的一部分，并且在器官培养中干扰雄性胚胎性腺的分泌会导致雄性生殖细胞向雌性性逆转。这些数据表明，胚胎支持细胞细胞生物学中发生的变化可能有助于在胚胎发育过程中将雄性性别决定信息传递给生殖细胞。
