NANOS2 acts as an intrinsic regulator of gonocytes-to-spermatogonia transition in the murine testes

In the male mouse embryos, the primordial germ cells colonize the developing testes at E11.5. These resident germ cells termed gonocytes are the predecessors of spermatogonial stem cells (SSCs) and differentiating spermatogonia. Both of which are essential for male fertility where the former maintains the continuity of spermatogenesis and the latter generates pioneering waves of spermatozoa. Therefore the timely initiation of gonocytes-to-spermatogonia transition (GST) is an important process during which the cell fates of gonocytes might be segregated. However, it is unknown whether gonocytes are composed of a heterogeneous mixture of germ cells with distinct differentiation potentials during GST. Here, we find that gonocytes exhibit heterogeneity in terms of the expression pattern of at least three early spermatogonial marker genes namely Nanos2, Stra8 and Gfra1. NANOS2 expression levels are negatively correlated with those of STRA8 and GFRA1 before GST, while positive correlation with GFRA1 is established after GST. We further find that overexpression of NANOS2 results in the repression of GFRA1 and PLZF in gonocytes, leading to a delay in GST. On the other hand, loss of NANOS2 results in the up-regulation of GFRA1 and PLZF, indicating a precocious entry of GST. Taken together, our data suggest that NANOS2 functions as an intrinsic timekeeper of GST in the mouse testes.