Figure 7. Models for the mechanism of female sex determination in mouse germ cells.

1. A model for the cell fate transitions and signaling requirements for the differentiation of fetal oocytes from the epiblast. PGC specification from the epiblast depends on the BMP signaling (Lawson et al, 1999; Saitou et al, 2002; Ohinata et al, 2009). The maturation from early‐to‐late PGCs depends on the DNA demethylation of key promoters, likely through passive as well as active mechanisms (Yamaguchi et al, 2012; Kagiwada et al, 2013), coupled with PGC propagation through SCF and cAMP signaling. The differentiation from late PGCs to fetal primary oocytes depends on the BMP and RA signaling.
2. A model for the roles of BMP and RA signaling. BMP and RA signaling contribute to the repression of early PGC genes (e.g., Prdm1, Prdm14, Tfap2c, Pou5f1, Sox2, Nanog, and Esrrb) and to the up‐regulation of late germ‐cell genes (e.g., Ddx4, Dazl, Piwil2, Mov10l1, and Mael) and fetal oocyte genes (e.g., Stra8, Rec8, Sycp3, Hormad1 as meiosis genes, and Figla, Ybx2, Sohlh2 as oocyte‐development genes). With BMP signaling, STRA8 promotes the expression of meiosis genes and inhibits the ectopic expression of developmental genes induced by RA signaling (RA genes). STRA8 does not have a significant impact on late germ‐cell genes and oocyte‐development genes. Without BMP signaling, STRA8 cannot fully up‐regulate meiosis genes or induce meiosis entry. BMP and RA signaling do not up‐regulate prospermatogonia genes.