4.8 Article

ZGLP1 is a determinant for the oogenic fate in mice

Journal

SCIENCE
Volume 367, Issue 6482, Pages 1089-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaw4115

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Funding

  1. Japan Society for the Promotion of Science (JSPS) Research Fellowship for Young Scientists
  2. JSPS [17H06098]
  3. JST-ERATO [JPMJER1104]
  4. HFSP [RGP0057/2018]
  5. Pythias Fund
  6. Open Philanthropy Project
  7. Grants-in-Aid for Scientific Research [17H06098] Funding Source: KAKEN

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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.

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