期刊
DEVELOPMENT
卷 144, 期 1, 页码 128-138出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.144642
关键词
Zar1; Zona pellucida; Oogenesis; p53; Zebrafish; Translational control; ER stress; Unfolded protein response; Apoptosis; Sex differentiation
资金
- National Natural Science Foundation of China [31590830, 31471359]
- Ministry of Science and Technology of the People's Republic of China [2013CB945000]
- Chinese Academy of Sciences [XDA01010108]
A large amount of maternal RNA is deposited in oocytes and is 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 RNA in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants that 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 marked 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 ZP gene 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.
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