Characterization of neuronal death and degeneration upon cell cycle re-entry in rux and APC/C mutants. Adriana De La Garza, Nicholas E. Baker. Albert Einstein College of Medicine, Bronx, NY.

   Roughex (rux) is a cyclin dependent kinase inhibitor that is required to maintain cell cycle exit in the Drosophila eye. In rux mutants R8 photoreceptor neurons re-enter the cell cycle as well as non-neuronal cells. Cycling R8 cells produce two distinct nuclei; however, they do not complete cytokinesis and one of the nuclei is often mobilized into the developing axon. The characteristics of this phenotype match those observed in mutants of universally conserved components of the Anaphase Promoting Complex. Since both R8 cells and other photoreceptor classes are missing from the rux mutant eye, it will be important to determine how these neurons are lost and whether there are autonomous or non-autonomous survival consequences of neuronal cell cycle entry. Genetic and labeling studies of rux are being used to identify the times, mechanisms, and locations where retinal cells are lost, and how this depends on the abnormal cell cycle events. If neuronal cell cycle re-entry is linked to neurodegenerative disease, as has been suggested many times previously, then these mechanisms may have some relevance to disease therapy.