The Analysis of Wdp, Sulf1, Wdp;Sulf1 Wing Discs and Genetic Interaction Between Heparan Sulfate and Chondroitin Sulfate Proteoglycans

Abstract

Morphogens are a type of signaling molecule that spreads out from their original source and specifies different cell fates in a concentration-dependent manner. Each cell within the concentration gradient receives a certain concentration of morphogen signals that bind to receptors on the cell surface and this creates a pattern of development. In this study, we looked at Heparan sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans. HSPGs are glycoproteins with covalently attached heparan sulfate chains and act as co-receptors for morphogen signaling molecules and control the rate of receptor-mediated endocytosis by stabilizing the receptor-ligand complex on the cell surface. Chondroitin sulfate proteoglycans (CSPGs) are major structural compliments of the extracellular matrix and CSPGs are also important in morphogen signaling. It was recently discovered that Windpipe (wdp), a CSPG, modulates Hedgehog signaling, and we want to understand if it affects other HSPG dependent pathways. The molecular mechanisms by which CSPGs and HSPGs exhibit co-receptor function are unknown and we are trying to understand if HSPGs and CSPGs exhibit dual proteoglycan co-receptor function. Therefore our research question is if these two proteoglycans have genetic interactions. Our hypothesis is that HSPGs and CSPGs have dual co-receptor function that controls receptor-mediated endocytosis and when there is a mutation in both proteoglycans, a synergistic effect is observed in the double mutant wdp;sulf1. The data thus far supports that HSPGs and CSPGs potentially do work together to regulate morphogen signialing.