ZGLP1 is a determinant for the oogenic fate in mice
ZGLP1 is a determinant for the oogenic fate in mice
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DOI：
10.1126/science.aaw4115
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发表时间：
2020-03-06
期刊：
影响因子：
56.9
通讯作者：
Saitou, Mitinori
中科院分区：
文献类型：
--
作者：
Nagaoka, So I.;Nakaki, Fumio;Saitou, Mitinori
生殖细胞的性别决定对于创造生殖细胞发育的性别二分法至关重要，从而确保有性繁殖。然而，潜在的机制仍不清楚。在这里，我们证明了ZGLP1，一个保守的转录调节因子，具有GATA样的锌指，决定了小鼠的卵子命运。ZGLP1作用于骨形态发生蛋白的下游，但不作用于维甲酸(RA)，对卵子发生程序和减数分裂进入是必不可少的。ZGLP1过表达通过激活受Polycomb活性抑制的卵子生成程序来诱导体外原始生殖细胞样细胞分化为胎儿卵母细胞，而RA信号有助于卵子生成程序的成熟和PGC程序的抑制。我们的发现阐明了哺乳动物卵源命运的决定机制，为促进体外配子发生和生殖医学提供了基础。
Sex determination of germ cells is vital to creating the sexual dichotomy of germ cell development, thereby ensuring sexual reproduction. However, the underlying mechanisms remain unclear. Here, we show that ZGLP1, a conserved transcriptional regulator with GATA-like zinc fingers, determines the oogenic fate inmice. ZGLP1 acts downstream of bone morphogenetic protein, but not retinoic acid (RA), and is essential for the oogenic program and meiotic entry. ZGLP1 overexpression induces differentiation of in vitro primordial germ cell-like cells (PGCLCs) into fetal oocytes by activating the oogenic programs repressed by Polycomb activities, whereas RA signaling contributes to oogenic program maturation and PGC program repression. Our findings elucidate the mechanism for mammalian oogenic fate determination, providing a foundation for promoting in vitro gametogenesis and reproductive medicine.