Figure 1.

Regulation of sex-specific germ cell development in the mouse gonad. As germ cells enter the genital ridge (future gonad) they undergo genome-wide demethylation, including reactivation of the X chromosome, erasure of imprints as well as chromatin remodelling. In a developing ovary, RA induces expression of the pre-meiotic gene Stra8 as well as a meiosis-associated gene, Rec8. STRA8 is critical for germ cell meiosis that is marked by up-regulation of Sycp3 and Dmc1 at about 13.5 dpc. In the developing testis, endogenous RA is degraded by a P450 enzyme, CYP26B1. FGF9 is present and acts directly on testicular germ cells to up-regulate Cripto, triggering active cell autonomous Nodal signalling that appears to maintain the pluripotent state. FGF9 also influences expression of later male fate markers. Activin and PGD2 influence the timing of mitotic arrest. Germ cells do not differentate along either female or male pathways unless they first express Dazl. Signaling molecules are shown in black ovals; unbroken arrows indicate a direct effect and broken arrows indicate an incompletely characterised or likely indirect effect.