In mouse fetal gonads, retinoic acid (RA) induces meiosis in the female germ cells, whereas the male germ cells never enter meiosis due to Cyp26b1-mediated RA metabolism. We show here that Nanos2 plays critical roles in the differentiation of male germ cells. We find that Nanos2 maintains the suppression of meiosis by preventing Stra8 expression, which is required for premeiotic DNA replication, after Cyp26b1 is decreased. We also demonstrate that Nanos2 activates a male-specific genetic program, which is supported by the inhibition of meiosis and the induction of male-type differentiation in female germ cells following the forced expression of Nanos2.
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