Department of Cell, Developmental, and Regenerative Biology. Icahn School of Medicine at Mount Sinai. One Gustave L. Levy Place Box 1020, New York, NY, USA.
Department of Molecular and Cellular Biology. University of California. 1 Shields Ave, Davis, CA, USA.
Nat Commun. 2024 Jun 19;15(1):5248. doi: 10.1038/s41467-024-49613-2.
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.
生殖成功依赖于生物性别的确立和维持。在许多动物中，包括哺乳动物，最初的主要性腺是偏向卵巢的。我们之前已经表明，RNA 结合蛋白（RNAbp）Rbpms2 是斑马鱼卵巢命运所必需的。在这里，我们鉴定了卵母细胞中的 Rbpms2 靶标（Rbpms2 结合的卵母细胞 RNA；rboRNA）。我们发现 Rbpms2 是 rboRNA 的翻译调节剂，其中包括睾丸因子和核糖体生物发生因子。此外，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 Gator2 组件、缺失卵母细胞（Mios）向 Rag 2（Gator2）的 Gap 活性。总之，我们的研究结果表明，早期的性腺细胞处于双重平衡、双潜能状态，其中 Rbpms2 充当二元命运开关。具体而言，Rbpms2 抑制睾丸因子，促进卵母细胞因子，通过必不可少的 Gator2 介导的检查点促进卵母细胞的进展，从而整合了斑马鱼卵发生中性别分化因子和营养可用性途径的调节。
