Francis R, Maine E, Schedl T
Department of Genetics, Washington University School of Medicine, St. Louis Missouri 63110, USA.
Genetics. 1995 Feb;139(2):607-30. doi: 10.1093/genetics/139.2.607.
The Caenorhabditis elegans gene gld-1 is essential for oocyte development; in gld-1 (null) hermaphrodites, a tumor forms where oogenesis would normally occur. We use genetic epistasis analysis to demonstrate that tumor formation is dependent on the sexual fate of the germline. When the germline sex determination pathway is set in the female mode (terminal fem/fog genes inactive), gld-1 (null) germ cells exit meiotic prophase and proliferate to form a tumor, but when the pathway is set in the male mode, they develop into sperm. We conclude that the gld-1 (null) phenotype is cell-type specific and that gld-1(+) acts at the end of the cascade to direct oogenesis. We also use cell ablation and epistasis analysis to examine the dependence of tumor formation on the glp-1 signaling pathway. Although glp-1 activity promotes tumor growth, it is not essential for tumor formation by gld-1 (null) germ cells. These data also reveal that gld-1(+) plays a nonessential (and sex nonspecific) role in regulating germ cell proliferation before their entry into meiosis. Thus gld-1(+) may negatively regulate proliferation at two distinct points in germ cell development: before entry into meiotic prophase in both sexes (nonessential premeiotic gld-1 function) and during meiotic prophase when the sex determination pathway is set in the female mode (essential meiotic gld-1 function).
秀丽隐杆线虫基因gld-1对卵母细胞发育至关重要；在gld-1（无效）的雌雄同体线虫中，通常发生卵子发生的部位会形成肿瘤。我们通过遗传上位性分析证明肿瘤形成取决于生殖系的性别命运。当生殖系性别决定途径设定为雌性模式（终端fem/fog基因失活）时，gld-1（无效）生殖细胞退出减数分裂前期并增殖形成肿瘤，但当途径设定为雄性模式时，它们发育成精子。我们得出结论，gld-1（无效）表型具有细胞类型特异性，且gld-1（+）在级联反应末端起作用以指导卵子发生。我们还使用细胞消融和上位性分析来研究肿瘤形成对glp-1信号通路的依赖性。尽管glp-1活性促进肿瘤生长，但它对于gld-1（无效）生殖细胞形成肿瘤并非必需。这些数据还表明，gld-1（+）在调节生殖细胞进入减数分裂之前的增殖中起非必需（且性别非特异性）作用。因此，gld-1（+）可能在生殖细胞发育的两个不同阶段对增殖起负调节作用：在两性进入减数分裂前期之前（非必需的减数分裂前gld-1功能）以及当性别决定途径设定为雌性模式时在减数分裂前期期间（必需的减数分裂gld-1功能）。
