Mesh : Animals Female Male Gene Expression Regulation, Developmental Mechanistic Target of Rapamycin Complex 1 / metabolism genetics Nutrients / metabolism Oocytes / metabolism Oogenesis / genetics Ovary / metabolism RNA-Binding Proteins / metabolism genetics Signal Transduction Testis / metabolism Zebrafish / genetics Zebrafish Proteins / metabolism genetics Nuclear Pore Complex Proteins / genetics metabolism

来  源:   DOI:10.1038/s41467-024-49613-2   PDF(Pubmed)

Abstract:
Reproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary biased. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes (Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator of rboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.
摘要:
生殖成功取决于适当建立和维持生物性别。在许多动物中,包括哺乳动物,初级性腺最初是卵巢偏向的。我们之前展示了RNA结合蛋白(RNAbp),Rbpms2是斑马鱼卵巢命运所必需的。这里,我们鉴定了卵母细胞中的Rbpms2靶标(Rbpms2结合的卵母细胞RNA;rboRNA)。我们将Rbpms2鉴定为rboRNAs的翻译调节因子,其中包括睾丸因子和核糖体生物发生因子。Further,遗传分析表明,Rbpms2通过mTorc1信号通路促进核仁扩增,特别是通过mTorc1激活针对Rags2(Gator2)组件的间隙活动,缺少卵母细胞(Mios)。累计,我们的研究结果表明,早期性腺细胞处于双重状态,双电势状态,其中Rbpms2充当二进制命运切换。具体来说,Rbpms2抑制睾丸因子并促进卵母细胞因子通过必需的Gator2介导的检查点促进卵母细胞进展,从而在斑马鱼卵子发生中整合性别分化因子和营养利用途径的调节。
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