This proposal asks the fundamental question of how complex cells, such as sensory neurons, maintain the functional identities they acquire during terminal differentiation. It builds on my recent results which showed that in one photoreceptor neuron subtype of fruit fly Drosophila melanogaster, a green-sensitive Rhodopsin6 (Rh6, a G-protein-coupled receptor that detects photons) not only functions in the phototransduction, but also signals to maintain repression of the sister receptor gene, the blue-sensing Rh5. This maintains in aging flies a mutually exclusive expression between the two Rhodopsins established during development. The signaling pathway that ensures this exclusion does not use key components of the phototransduction cascade and thus represents a new molecular pathway downstream of Rhodopsin signal. The main goal of this proposal is to elucidate the transduction pathway which mediates the Rhodopsin exclusion signal: Objective 1. Using Drosophila genetics I will focus on the role of negative modulators of phototransduction, Arrestin2 and Gprk1, in Rh5/Rh6 exclusion mechanism. Preliminary results suggest that loss of these genes leads to de-repression of Rh6 in blue photoreceptors, an “opposite” phenotype to loss of Rh6. These results will allow me to establish the logic of Rhodospin cross-regulation. Objective 2. Based on strong preliminary evidence, I will determine the role that Hippo tumor suppressor pathway plays in transducing the Rhodopsin signal. This will provide important information about new upstream regulators of the Hippo pathway. 3. I will exploit my discovery of variability in Rh5/Rh6 expression patterns in wild flies to identify genes involved in the mutual exclusion of the blue and green Rhodopsins and to understand the ecology and evolution of fly color vision. This proposal will directly impact our understanding of aging of sensory systems and the role that Hippo pathway plays in this process.
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