Inhibition of primordial germ cell proliferation by the medaka male determining gene Dmrt I bY.
Inhibition of primordial germ cell proliferation by the medaka male determining gene Dmrt I bY.
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DOI：
10.1186/1471-213x-7-99
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发表时间：
2007-08-30
影响因子：
--
通讯作者：
Schartl, Manfred
中科院分区：
文献类型：
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作者：
Herpin, Amaury;Schindler, Detlev;Kraiss, Anita;Hornung, Ute;Winkler, Christoph;Schartl, Manfred
Dmrt1是一个高度保守的基因，参与脊椎动物原始性腺的决定和早期分化阶段。在青鳉鱼中，dmrt1bY 是 Y 染色体上常染色体 dmrt1a 基因的功能性复制品，已被证明是雄性性腺发育的主要调节因子，与哺乳动物中的 Sry 相当。在雄性中，在形态性别分化之前，在性腺原基原始生殖细胞 (PGC) 周围的体细胞中观察到 mRNA 和蛋白质表达，随后仅在支持细胞中观察到 mRNA 和蛋白质表达。这表明 dmrt1bY 在男性性腺和生殖细胞发育过程中发挥作用。我们提供的功能证据表明 dmrt1bY 的表达会导致 PGC 增殖的负调节。流式细胞仪测量显示 dmrt1bY 表达细胞出现 G2 停滞。有趣的是，未转染的细胞也显示出明显较低的增殖细胞比例，表明 dmrt1bY 可能具有非细胞自主作用。由于增殖抑制作用丧失，注射反义吗啉导致遗传性雄性胚胎中 PGC 增加。在青鳉中，dmrt1bY 在性别决定阶段的睾丸分化之前介导雄性 PGC 有丝分裂停滞。这可能是通过支持细胞和 PGC 的交互作用发生的。
Dmrt1 is a highly conserved gene involved in the determination and early differentiation phase of the primordial gonad in vertebrates. In the fish medaka dmrt1bY, a functional duplicate of the autosomal dmrt1a gene on the Y-chromosome, has been shown to be the master regulator of male gonadal development, comparable to Sry in mammals. In males mRNA and protein expression was observed before morphological sex differentiation in the somatic cells surrounding primordial germ cells (PGCs) of the gonadal anlage and later on exclusively in Sertoli cells. This suggested a role for dmrt1bY during male gonad and germ cell development. We provide functional evidence that expression of dmrt1bY leads to negative regulation of PGC proliferation. Flow cytometric measurements revealed a G2 arrest of dmrt1bY expressing cells. Interestingly, also non-transfected cells displayed a significantly lower fraction of proliferating cells, pointing to a possible non-cell autonomous action of dmrt1bY. Injection of antisense morpholinos led to an increase of PGCs in genetically male embryos due to loss of proliferation inhibition. In medaka, dmrt1bY mediates a mitotic arrest of PGCs in males prior to testes differentiation at the sex determination stage. This occurs possibly via a cross-talk of Sertoli cells and PGCs.