Hedgehog pathway members Patched and Costal-2 exhibit differences in overgrowth autonomy in Drosophila melanogaster

Abstract

Genetic screens are used in Drosophila melanogaster to identify genes key in the regulation of organismal development and growth. These screens have defined signaling pathways necessary for tissue and organismal development which are evolutionarily conserved across species, including Drosophila. Here we have used a Flp/FRT mosaic system to screen for conditional regulators of cell growth and cell division in the Drosophila eye. The conditional nature of this screen utilizes a block in the apoptotic pathway to prohibit the mosaic mutant cells from dying via apoptosis. From this screen, we identified two different mutants that mapped to the Hedgehog signaling pathway. Previously, we described a novel Ptc mutation and here we add to the understanding of disrupting the Hh pathway with a novel allele of Cos2. Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth. Ptc mutations lead to overgrowth consisting of almost entirely wild type issue (non-autonomous overgrowth), while the Cos2 mutation results in tissue that is overgrown in both the mutant and wild type clones (both autonomous and non-autonomous). These differences in tissue overgrowth are consistent in the Drosophila eye and wing. The observed difference is correlated with a different pattern of deregulation of Mad, the downstream effector of DPP signaling. This finding provides insight into pathway specific differences that may help to better understand intricacies of developmental processes and human disease.