The decapentaplegic gene complex (DPP-C) in the fruit fly, Drosophila melanogaster, contains several integrated functional units necessary for normal epidermal development. Discrete genetic units within the DPP-C are required for the development of specific epidermal subpopulations. It is not definitively established if any other tissue types require normal DPP-C activity for their normal development. Mutations in one region of the complex (dpp) cause dramatic pattern effects on developing imaginal disks. Lesions in another region (Hind) causes abnormal gastrulation, segmentation and dorsal epidermal development in the embryo. Alterations in the third region (shv) have mild effects on two developing imaginal disks, but many of these alleles also cause larval death. The major goals of this project are (1) to define the structure of the DPP-C, (2) to delineate the relationship between that structure and the regulation of the various DPP-C gene products, (3) to isolate and characterize those gene products, and (4) to understand the developmental role(s) of this gene complex. Our present working hypothesis is that the DPP-C is involved in the elaboration or recognition of positional signals in developing epidermal tissues. If this hypothesis is borne out, the DPP-C would occupy a novel position in the hierarchy of developmentally defined functions in Drosophila. Given the phenomenological similarities between insect appendage formation and vertebrate limb development, our studies might have important medical implications. The ability to control the proliferation of epidermal cells in response to positional cues can provide important tools for use in treating a number of congenital malformations such as limb defects as well as a variety of conditions cause by accidental damage (e.g., amputations). In addition, it is very likely that a serious understanding of neoplasia demands that normal development and growth regulation first be understood. The DPP-C may provide important information toward this end. This project will involve a multi-faceted genetical, developmental and molecular biological approach aimed at a complete dissection of the DPP-C. As an offshoot of the initial project, the phenomenon of transvection at the DPP-C will be utilized to study some aspects of the architecture of the somatic nucleus in Drosophila. Such studies will be aimed toward determining if the higher order structure of the nucleus can control or respond to different developmental states.
