Modular tissue-specific regulation of doublesex underpins sexually dimorphic development in Drosophila

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-naive\" 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.\n\nSummary StatementWe 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.