Patterning of Drosophila Sense Organs via Global Activation and Repression of the Proneural Gene achaete

During vertebrate and invertebrate development, organs and tissues must be precisely patterned, and periodic proneural gene expression is an early and essential event in this process. The Drosophila melanogaster sensory bristles are a good model system to study the molecular mechanisms involved in controlling precise proneural gene expression. There are two classes of sensory bristles: early specified (mechanosensory macrochaetae and chemosensory microchaetae) and late specified (mechanosensory microchaetae) bristles. Previous studies suggest that patterning of early-specified bristles requires induction of proneural gene expression at specific locations in the limb and body wall primordia. Proneural gene expression in primordia of early-specified bristles is controlled by discrete modular cis-regulatory elements (CRE). Our studies, however, suggest that a different mechanism is used to pattern late specified bristles: expression of the proneural gene, achaete (ac), in primordia of late specified bristles is controlled by a single CRE. On the surface of the Drosophila leg, small mechanosensory microchaetae (mC) are organized in a series of longitudinal rows along the leg circumference. In the prepupal leg, ac is expressed in longitudinal stripes, which comprise the leg microchaete primordia. We have found that Hairy (H) and Delta/Notch (Dl/N) signaling function concertedly and non-redundantly to define periodic ac expression. This process involves broad and late activation of ac expression and refinement in response to a prepattern of repression, which is established by Hairy and Delta. These findings have allowed us to formulate a general model for generation of periodic bristle patterns in the adult leg, and this model is supported by the analysis of a CRE, called the ac-mC-CRE, that specifically directs ac expression in the leg and notal mC proneural fields. This CRE contains an activation element, which directs broad expression of ac along the circumference of prepupal legs, and a repression element, which is Hairy and Dl/N responsive. To gain insight into the molecular mechanisms that mediate repression by Hairy and Notch, we undertook a detailed analysis of the ac-mC-CRE. Our findings provide novel insight into repression of proneural ac expression by bHLH repressor, Hairy, and Notch, which acts through the bHLH Enhancer of split E(spl) repressors. We find that Hairy and E(spl) can mediate repression of ac via common sequences in the ac promoter and ac-mC-CRE. This finding has interesting implications regarding the evolution of morphological novelty in mC patterning.