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Analysis of the Multiple Roles of Gld-1 in Germline Development: Interactions with the Sex Determination Cascade and the Glp-1 Signaling Pathway

机译:Gld-1在生殖细胞发育中的多重作用分析:与性别决定级联和Glp-1信号通路的相互作用

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摘要

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).
机译:秀丽隐杆线虫基因gld-1对于卵母细胞发育至关重要。在gld-1(无)雌雄同体中,通常会发生卵子形成的肿瘤。我们使用遗传上位分析来证明肿瘤的形成取决于种系的性命。当种系性别决定途径设置为女性模式(末端fem / fog基因无效)时,gld-1(空)生殖细胞退出减数分裂前期并增殖形成肿瘤,但是当该途径设置为男性模式时,他们发展成精子。我们得出的结论是,gld-1(null)表型是特定于细胞类型的,并且gld-1(+)在级联反应的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检查肿瘤形成对glp-1信号通路的依赖性。尽管glp-1活性促进肿瘤生长,但对于gld-1(空)生殖细胞形成肿瘤不是必需的。这些数据还表明,gld-1(+)在进入生殖细胞减数分裂之前,在调节生殖细胞增殖中起着非必需的作用(以及性别非特异性)。因此,gld-1(+)可能在生殖细胞发育的两个不同点上负调控增殖:男女进入减数分裂前期(非必要的减数分裂前gld-1功能)和减数分裂前期(在雌性中确定性别决定途径)模式(基本减数分裂gld-1功能)。

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