Abstract The ability of a single genome to produce distinct and often dramatically different male and female forms is one of the wonders of animal development. In most animals, sex-specific phenotypes are shaped by interactions between a sex determination pathway and spatial patterning gene networks. In Drosophila melanogaster , most sexually dimorphic traits are controlled by sex-specific isoforms of the doublesex ( dsx ) transcription factor, and dsx expression is mostly limited to cells that give rise to sexually dimorphic traits. However, it is unknown how this mosaic of “sex-naïve” and “sex-aware” tissues arises. Here, we characterize the cis -regulatory sequences that control dsx expression in the foreleg, which contains multiple types of sex-specific sensory organs. We find that separate modular enhancers are responsible for dsx expression in each sexually dimorphic organ. Expression of dsx in the sex comb is co-regulated by two enhancers with distinct spatial and temporal specificities that are separated by a genitalia-specific enhancer. Thus, the mosaic of sexually dimorphic and monomorphic organs depends on modular regulation of dsx transcription by dedicated cell type-specific enhancers. Summary Statement We identify the modular cis -regulatory elements that direct expression of doublesex in sexually dimorphic structures in Drosophila legs and genitalia. This regulatory landscape provides insight into how cells obtain their sex-specific identity.

Modular tissue-specific regulation ofdoublesexunderpins sexually dimorphic development inDrosophila