My laboratory seeks to understand how neurons regulate their survival. One major goal is to determine the genes that regulate photoreceptor cell death in response to putative misfolding mutants of opsin. We have investigated whether genes known to regulate cell death in developing tissues also regulate photoreceptor cell death in the adult. We have also refined an assay that we developed for saturation screening of genetic modifiers of retinal degeneration. We have found that apoptosis induced by the opsin mutants is regulated by at least two signaling pathways, whose makeup and interdependence is under investigation. As an important part of these studies, we have designed and constructed modified genetic lines and behavioral assays with which we are investigating the effect of the Rh1 opsin mutations on folding and function in vivo, in isolation from the function of Rh2-6 opsins. While investigating the role of one family of cell survival proteins in neuronal maintenance, we discovered the Drosophila homolog of TRAF4, and a dominant negative version thereof. We determined that dTRAF is required for normal neurogenesis and myogenesis. Also, at least one of its roles in neurogenesis is as a regulator of axon guidance. We are in the process of determining its place in a molecular signaling pathway with which we have found genetic interaction. Null and ectopically expressing dTRAF lines have been constructed, which we are using to investigate its role in adult neuronal survival.
