The glypican Dally shapes follicle cell patterning by regulating the epidermal growth factor receptor ligand Gurken

Heparan sulfate proteoglycans (HSPGs) have been shown to interact with morphogens of many signaling pathway. During Drosophila oogenesis, the major contributors to tissue patterning are the bone morphogenic protein (BMP) and epidermal growth factor receptor (EGFR) signaling pathways. It was previously shown that BMP signaling is regulated by the HSPG, dally (division abnormally delayed), in the wing, and also in patterning of the follicle cells (FCs). The EGFR pathway is responsible for axis determination as well as follicle cell pattering. Using genetic perturbation, we demonstrate that Dally regulates the distribution of EGFR signaling through the restriction of the TGFα-like ligand Gurken (GRK). When dally is perturbed by uniform overexpression or depletion in the FCs, the GRK gradient is either narrowed, or widened, respectively. In these backgrounds, changes in EGFR activation, measured by dpERK, are consistent with the shapes of GRK patterning. These effects on EGFR activation lead to corresponding results on follicle cell pattering where a decrease in midline clearing of BR in overexpression of dally, corresponding to a reduced gap between the dorsal appendages (DAs). Expressing a mutant form of Dally, lacking an anchor to the membrane, perturbed the GRK gradient, leading to tissue patterning and eggshell morphology defects. Based upon these results, we propose that Dally is required for the formation of the GRK gradient for optimal EGFR signaling activation.M.S.Includes bibliographical referencesby Steven Harris Brownstei