The Regulation of Growth Factor Signaling in Drosophila Development and Disease

Abstract

Developmental signaling pathways have many diverse roles throughout the life of an organism. The proper regulation of these pathways is essential for normal development, and misregulation can lead to diseases such as cancer. Heparan sulfate proteoglycans function to modulate growth factor signaling in many biological processes by acting as co-receptors, or by influencing ligand distribution. The heparan sulfate proteoglycan Trol, the Drosophila Perlecan homolog, is known to modulate signaling in a population of neuroblasts in the developing Drosophila central nervous system. My studies aim to determine the function Trol has in regulating signaling pathways during development. trol mutants are examined to determine how various mutant alleles impact signaling in several different developmental contexts. The role growth factor pathways play during induction of a Drosophila prostate cancer model is also examined. Gene expression profiles are determined for two types of prostate model overproliferation. Trol is shown to be able to differentially regulate multiple signaling pathways during several developmental processes. The Drosophila prostate cancer model is also shown to have many characteristics similar to those of human prostate cancer, and that signaling and proteoglycan expression are impacted by aberrant overgrowth in the model. My results indicate that Trol is able to specifically modulate different signaling pathways depending on the tissue and developmental context.