Mitosis in neurons: Roughex and APC/C maintain cell cycle exit to prevent cytokinetic and axonal defects in Drosophila photoreceptor neurons. Nick Baker¹, Robert Ruggiero¹, Abhijit Kale¹, Barbara Thomas². 1) Genetics, Albert Einstein College of Medicine, Bronx, NY; 2) Laboratory of Biochemistry, National Cancer Institute, Bethesda, MD.

   Neural function is facilitated by the stable, post-mitotic status of the neurons. Little has been known about the mechanisms of neuronal cell cycle withdrawal, and there are few reports of mutations that affect it. We find three genes where mutations lead to cell cycle re-entry during terminal differentiation by a particular class of developing photoreceptor neurons in the fly retina. Strikingly, these neurons do not complete cell division but only divide their nuclei, failing to develop a contractile ring or to perform cytokinesis. Most of the resulting bi-nucleated neurons retain one nucleus in its normal location in the cell body, while transporting the other nucleus towards the growth cone in a kinesin-dependent manner resembling anterograde axonal transport. Our findings identify Cyclin A regulation as crucial to maintaining cell cycle exit by these neurons, and a neuron-specific defect in cytokinesis as a further barrier to neuron proliferation. Because defects in transporting axonal material have been implicated in multiple neurodegenerative diseases, our findings raise the possibility of a connection between defective cell cycle regulation in neurons and neuronal cell death related to defective axonal trafficking.