Molecular genetic analysis of drosophila disconnected gene during development

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The Drosophila disconnected (disco) gene encodes a C2H2 type zinc finger transcription factor required for the development of central and peripheral nervous system.  disco expression during development is dynamic, suggesting a role for this gene in a variety of developmental processes. During the previous funding period we have investigated a novel function for disco in the patterning of Proximal -Distal (P-D) axis during leg and antennal development. The P-D axis refers to the way insect  appendages (or limbs) are organized from the portion closest to the body (proximal) to the structures that make the ti[p of the appendage. In vertebrates as well as insects the Distal-less (Dll) gene represents the master regulator of this important developmental process.Our results implicated disco in Dll-dependent leg and antenna development and in the proper expression of Dll.  Down regulation of disco gene function in Dll domain mimics Dll mutation phenotypically and molecularly. Moreover up regulation of disco in Dll cells in a Dll mutant background partially rescues the mutant phenotype.  Our results demonstrate that disco and Dll participate in an auto regulatory feedback loop where Dll is required and sufficient for disco promoter activity and disco in turn is required for proper Dll transcription. Thus I propose as a working hypothesis that disco carries out its function in P-D patterning as a cofactor of Dll. Most interestingly our results suggest that disco may be required in the antenna as an inhibitor of retinal cell fate by restricting the expression of dachshund (dac).In this grant application I outline several experiments aimed at continuing our investigations of the role of disco in appendage development and its relationship to Dll dependent P-D development. In addition, I propose to extend these studies to the relationship between Dll and disco function in cell fate allocation in the visual primordium and in the eye antennal imaginal disc.