一种能阻止性别反转的关键基因

来自中科院遗传与发育生物学的研究人员发表了题为“Translation repression by maternal RNA binding protein zar1 is essential for early oogenesis in zebrafish”的文章，发现斑马鱼zar1基因对于早期卵子发生及雌性发育至关重要，如果缺失zar1编码的蛋白，雌性斑马鱼就会性别反转为雄性。这一研究揭示了zar1基因的生物学功能及其分子作用机制，促进了对斑马鱼的性别决定及性别分化的了解。

这一研究成果在线发表在Development杂志上，研究由遗传与发育生物学研究所张建研究组、汪迎春研究组，以及中国科学院动物研究所陈大华研究员等合作完成，第一作者为张建研究组的博士研究生苗丽云。

性别决定与性别分化对于有性繁殖生物的繁衍至关重要。鱼类性别决定机制的研究不仅有助于渔业生产，而且有助于性别决定机制的进化研究。模式动物斑马鱼的性别决定及性别分化机制尚不清楚。

成年斑马鱼仅具有一套生殖系统（雄性或雌性），而幼年时期的斑马鱼却具有向两种性别方向发育的潜能。卵母细胞对于斑马鱼向雌性方向的发育是至关重要的。脊椎动物的卵子中存储了大量的母源信息以支持卵母细胞和早期胚胎发育。大量研究显示卵子成熟过程涉及非常严密的mRNA翻译调控，但母源因子如何调控早期卵母细胞mRNA的翻译却知之甚少。

这项新研究获得了脊椎动物早期卵母细胞的翻译调控方面的新进展。研究人员通过突变体分析，发现斑马鱼的zar1基因对于早期卵子发生及雌性发育至关重要。

Zar1蛋白通过结合透明带糖蛋白mRNA并抑制其翻译。如果缺失Zar1蛋白导致卵母细胞中多个透明带糖蛋白的过量表达，而这些蛋白的过度积累可引起内质网应激并最终导致卵母细胞凋亡，进而导致卵巢被精巢所取代，雌性斑马鱼性别反转为雄性。这一研究揭示了zar1基因的生物学功能及其分子作用机制，促进了对斑马鱼的性别决定及性别分化的了解。（来源：生物通）

Translation repression by maternal RNA binding protein zar1 is essential for early oogenesis in zebrafish

Abstract Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNAs in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants which result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development. zar1 immature ovaries show upregulation of proteins implicated in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). More importantly, loss of Zar1 causes markedly upregulation of zona pellucida (ZP) family proteins, while overexpression of ZP proteins in oocytes causes upregulation of stress related activating transcription factor 3 (atf3), arguing that tightly controlled translation of ZP proteins is essential for ER homeostasis during early oogenesis. Furthermore, Zar1 binds to zona pellucida (zp) mRNAs and represses their translation. Together our results indicate that regulation of translational repression and de-repression are essential for precisely controlling protein expression during early oogenesis.

原文链接：http://dev.biologists.org/content/early/2016/12/01/dev.144642