Figure 2.

The antagonistic relationship between the pathways determining testis or ovary development in mammals. The male-determining pathway is shown on the left and the female pathway on the right. In males, SRY on the Y chromosome is activated by various upstream factors (small green arrows), including SF1, and upregulates the autosomal gene SOX9, which then maintains its own activity with the help of several other factors (small green arrows), including FGF9, whose expression is in turn upregulated by SOX9. FGF9 induces a cascade of downstream steps that is controlled by several genes, including DMRT1. These steps culminate in the differentiation of Sertoli cells, which are crucial to the development of the gonad as a testis. SOX9 and FGF9 repress RSPO1 and WNT4, which promote the development of the gonad as an ovary. In females, RSPO1 upregulates WNT4, which is accompanied by the stabilization of β-catenin, which is probably the mediator by which RSPO1 and WNT4 repress SOX9 and FGF9. Activation steps are represented by green arrows and inhibition by red bars.