Fig. 1. The Drosophila somatic sex-determination hierarchy. The ratio of X chromosomes to sets of autosomes determines the on/off state of the Sex-lethal (Sxl) gene. In females, where the X:A ratio is 1, active SXL protein is made and its production is maintained via autoregulation. The presence of SXL causes splicing of the transformer (tra) pre-mRNA such that active TRA protein is made. When TRA is present with the protein product of the transformer-2 (tra-2) gene, the pre-mRNA of the doublesex (dsx) gene is spliced into its female-specific form, which encodes the DSX^F protein. Similarly, the pre-mRNAs from the 5'-most promoter of the fruitless (fru) gene are spliced in a female-specific manner, and do not produce any detectable protein (three other promoters of fru produce transcripts that do not differ between the sexes). DSX^F interacts with the products of the hermaphrodite (her) and intersex (ix) genes to activate female terminal differentiation and to repress male terminal differentiation. In males, where the X:A ratio is 0.5, no active SXL is made, so the tra pre-mRNA is spliced into its default, male-specific form, which does not produce active TRA protein. Although it is present in males, TRA-2 cannot act without active TRA, so the dsx and fru pre-mRNAs are spliced into default, male-specific forms. The male-specific DSX^M protein activates male terminal differentiation and represses female terminal differentiation, interacting to some extent with HER. Although ix is expressed in males, like tra-2 it has no detectable function. The male-specific FRU^M protein activates male courtship behavior. Arrows indicate positive regulation, bars indicate negative regulation and gray shading of gene names indicates that active proteins are not produced in the given sex.