Yao Humphrey Hung-Chang, Tilmann Christopher, Zhao Guang-Quan, Capel Blanche
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Novartis Found Symp. 2002;244:187-98; discussion 198-206, 253-7.
In mammals, a primordial gonad forms in XY and XX embryos that develops into a testis or an ovary depending on expression of Sry. Sry induces cell signalling pathways, including proliferation of Sertoli precursors and migration of peritubular myoid and vascular cells from the mesonephros. These events result in increased testis size and testis cord organization. Testis cord formation normally prohibits germ cells from entering meiosis. Ovarian fate is initiated in the absence of Sry, and has been proposed to be dependent upon the presence of meiotic germ cells in the gonad. We have shown that a developmental window exists during which testis development can be experimentally induced in XX gonads. This window closes just prior to the time that germ cells enter meiosis. Based on our work and much work that has preceded it, we suggest that the autonomous entry of germ cells into meiosis initiates the ovarian pathway and blocks testis development. Sry opposes this pathway by initiating testis cord formation prior to meiosis which sequesters germ cells inside cords and arrests them in mitosis. Current experiments in the lab address the hypothesis that cord formation and germ cell entry into meiosis are competing pathways in gonad development.
在哺乳动物中，XY和XX胚胎会形成原始性腺，该性腺会根据Sry的表达情况发育成睾丸或卵巢。Sry会诱导细胞信号通路，包括支持细胞前体的增殖以及中肾的睾丸间质肌样细胞和血管细胞的迁移。这些事件会导致睾丸体积增大和睾丸索形成。睾丸索的形成通常会阻止生殖细胞进入减数分裂。在没有Sry的情况下会启动卵巢发育命运，并且有人提出这取决于性腺中减数分裂生殖细胞的存在。我们已经表明，存在一个发育窗口期，在此期间可以通过实验诱导XX性腺发育成睾丸。这个窗口期恰好在生殖细胞进入减数分裂之前关闭。基于我们的工作以及之前的大量研究，我们认为生殖细胞自主进入减数分裂会启动卵巢发育途径并阻止睾丸发育。Sry通过在减数分裂之前启动睾丸索形成来对抗这一途径，睾丸索形成会将生殖细胞隔离在索内并使其停滞在有丝分裂阶段。实验室目前的实验探讨了这样一个假设，即索的形成和生殖细胞进入减数分裂是性腺发育中的竞争途径。
