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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.Supplemental material is available at http://www.genesdev.org.

Maintaining Germline Stem Cells Spermatogonial stem cell pools in postnatal testes have to be maintained to continuously generate spermatozoa. It has been difficult to identify these stem cells in vivo, because of their small numbers and lack of appropriate molecular markers, but now Sada et al. (p. 1394 ) show that the RNA-binding protein NANOS2 is expressed in a small subset of spermatogonia that behave as self-renewing stem cells in intact testes. By a combinatorial use of loss- and gain-of-function studies, NANOS2 was found to be essential for the maintenance of the immature state of spermatogonial stem cells by supporting their self-renewing properties and by suppressing differentiation.

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