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. 1999 Sep 10;65(4):933–942. doi: 10.1086/302601

Figure 2.

Figure 2

Mammalian sex determination: a molecular view. Factors implicated in formation of the bipotential gonad and differentiation of the ovary and testis are shown. Testis determination is initiated by SRY; however, molecular downstream targets of SRY and direct connections of SRY with other regulatory factors are undetermined. During testis differentiation, Sox9, SF-1 and WT-1 regulate MIS. SF-1 also directs expression of steroidogenic enzymes to produce testosterone and the Insl-3 factor, which is required for proper testis descent. Mutation of SRY, SOX9, SF-1, or WT1 leads to 46,XY sex-reversed females. An additional dose of the DAX1 gene (or increased DAX1 protein) is postulated to result in 46,XY sex reversal by direct antagonism of SF-1. By contrast, Wnt-4 blocks production of testosterone and therefore may block segments of the male program in the ovary. The placement of DMRT1 in this pathway remains uncertain. Cross-regulation of SRY, SOX9, SF-1, WT-1, and DAX1 may occur at multiple levels and is not depicted here.