Dmrt genes integrate sex-specific, spatial, and temporal cues to induce sexually dimorphic differentiation in restricted groups of cells. A. In the D. melanogaster sex comb, dsx is controlled by the splicing-based sex determination pathway (red), the HOX gene Scr and intrasegmental positional cues (green), and presumably by ecdysone signaling that regulates the timing of metamorphosis (purple). dsx induces sex comb development by controlling cell fate decisions and several distinct morphogenetic processes [34]. B. In C. elegans, dmd-3 and mab-3 are controlled by the sex determination pathway (red), by posterior group HOX genes, Wnt signaling and GATA transcription factors (green), and by the heterochronic pathway (purple). dmd-3 and mab-3 induce male-specific tail differentiation by regulating cell-autonomous morphogenetic processes as well as signaling pathways including TGF-β (sma-3) and Rho kinase (vav-1). In both organisms, arrows indicate either direct or indirect regulation [43,46].