Fig. 2. Regulatory cascades in D. melanogaster and mammalian sex determination involve factors acting upon pre-mRNA splicing. In the fly (left) SXL positively regulates TRA expression and downregulates MSL-2 in female flies. TRA-TRA2 heterodimers trigger expression of the female-specific DSX^F isoform. In the absence of SXL, males express DSX^M. In mammals (right), WT1(+KTS) isoforms upregulate Sry in the developing male gonad. Sry, in turn, negatively influences the expression — or the function — of an unknown Z gene, which inhibits testis differentiation genes. Z gene candidates are indicated (pink box).