A Distalless-responsive enhancer of the Hox gene Sex combs reduced is required for segment- and sex-specific sensory organ development in Drosophila

Hox genes are involved in the patterning of animal body parts at multiple levels of regulatory hierarchies. Early expression of Hox genes in different domains along the embryonic anterior-posterior (A/P) axis in insects, vertebrates, and other animals establishes segmental or regional identity. However, Hox gene function is also required later in development for the patterning and morphogenesis of limbs and other organs. In Drosophila, spatiotemporal modulation of Sex combs reduced (Scr) expression within the first thoracic (T1) leg underlies the generation of segment- and sex-specific sense organ patterns. High Scr expression in defined domains of the T1 leg is required for the development of T1-specific transverse bristle rows in both sexes and sex combs in males, implying that the patterning of segment-specific sense organs involves incorporation of Scr into the leg development and sex determination gene networks. We sought to gain insight into this process by identifying the cis-and trans-regulatory factors that direct Scr expression during leg development. We have identified two cis-regulatory elements that control spatially modulated Scr expression within T1 legs. One of these enhancers directs sexually dimorphic expression and is required for the formation of T1-specific bristle patterns. We show that the Distalless and Engrailed homeodomain transcription factors act through sequences in this enhancer to establish elevated Scr expression in spatially defined domains. This enhancer functions to integrate Scr into the intrasegmental gene regulatory network, such that Scr serves as a link between leg patterning, sex determination, and sensory organ development.