Figure 1.

A summary of p38 MAPK signalling in sex determination in mice. (a) A diagrammatic representation of the sex fate decision of Sertoli cells. At around 10.5 dpc, p38 MAPK is activated by the GADD45γ/MAP3K4/MAP2K6 pathway. Then, p-p38 MAPK activates GATA4 by phosphorylation and subsequent expression of SRY. SRY upregulates SOX9 and FGF9 expression to induce differentiation into Sertoli cells (black arrows). At 12.5 dpc, testis cords have formed and morphological differences between the testis (blue) and the ovary (pink) are evident. Both inhibition and overactivation of p38 MAPK cause delayed onset and reduced expression of SRY, which permits WNT4 and RSPO1 to express in a female-specific manner, inducing ovarian development (red arrows). (b) A schema for the sex fate decision of XY PGCs. In XY gonads, the SRY-SOX9-FGF9 pathway prevents XY PGCs from differentiating into female germ cells by blocking the network of RA/STRA8 through CYP26B1. p38 MAPK signalling is activated in PGCs of XY gonads around E11.5 dpc and induces the expression of Nanos2. Nanos2 inhibits the expression of STRA8 to block PGCs from entering meiosis and promotes a male differentiation in XY PGCs (black arrows). The inhibition of p38 MAPK permits the expression of STRA8 in PGCs (red arrows).