The goal of this proposal is to understand the molecular biology of epithelial morphogenesis in Drosophila imaginal discs at metamorphosis. Restructuring of imaginal discs into the adult insect appendages requires extensive short distance rearrangements of cells within the continuous epithelium, a widespread morphogenetic mechanism. In Drosophila these morphogenetic events are initiated by the steroid hormone 20- hydroxyecdysone and can be studied using in vitro culture of mass-isolated imaginal discs. It has been possible to isolate and characterize hormone-responsive genes that are activated during morphogenesis. This proposal will focus on a genetic and molecular analysis of the regulation and function of one gene, IMP-E1 (Inducible Membrane Protein-Early, transcriptionally active in the initial stages of imaginal disc morphogenesis. Gene function will be investigated genetically by isolation and analysis of mutations that alter the effectiveness of the gene product. A biochemical investigation of function will utilize immunological studies with an antisera produced against a fusion protein synthesized in a bacterial expression system. The mechanism of steroid hormone regulation of expression of this gene will be determined and the fine- structure of the gene analyzed. This proposal will further our understanding of the molecular biology of morphogenesis and the genetic mechanisms by which complex processes like morphogenesis are controlled during development. %%% Dr. Natzle proposes to investigate the properties of a gene that may be essential for the normal formation of adult tissue during the development of an insect. She has identified a gene that responds to a hormone that induces the formation of adult tissue. By analyzing the regulation of this gene at a genetical and biochemical level, Dr. Natzle will obtain basic information concerning the function of this gene in the process of normal morphogenesis. An understanding of the molecular choreography of morphogenesis may enable us to better analyze developmental abnormalities that occur when normal morphogenesis is perturbed or when cells within a tissue fail to retain their normal interactions with neighbors and substratum and produce invasive neoplasia.
