TRANSCRIPTIONAL CONTROL OF PHOTORECEPTOR AXON GROWTH AND TARGETING IN DROSOPHILA MELANOGASTER by JONATHAN

Original approval signatures are on file with the University of Oregon Graduate School. The nervous system is required for human cognition, motor function, and sensory interaction. A complex network of neuronal connections, or synapses, carries out these behaviors, and defects in neural connectivity can result in developmental and degenerative diseases. In vertebrate nervous systems, synapses most commonly occur at axon terminals. Upon reaching their synaptic targets, growth cones lose their motility and become boutons specialized for neurotransmitter release. I am studying this process in R7 photoreceptors in the Drosophila visual system. In a forward genetic screen, we identified the transcriptional repressor Tramtrack69 (Ttk69) as being required to prevent R7 axon terminals from expanding and overlapping with adjacent R7 targets. Loss of Ttk69 results in R7 axons that grow into neighboring terminals, while premature expression of Ttk69 in R7s prevents their axons from reaching their final target. From this I conclude that Ttk69 is both necessary and sufficient to inhibit R7 axon growth and that the timing of Ttk69 expression is critical to R7 target selection. Rather than forming mature synaptic boutons, ttk69 mutant R7s develop oversized terminals with ectopic filopodia-like protrusions, suggesting a failure to transition from growth to synapse formation. However, Ttk69 appears to regulate axon growth v independently of synaptogenesis, as I have found that the overgrowth of ttk69 mutant R7 axons does not depend on the ability of R7s to form synapses nor does it disrupt the initial steps of synapse formation. To identify the genetic program downstream of Ttk69, I have taken both a genetic and a candidate gene approach. It was previously shown that loss of Activin signaling causes mild overgrowth of R7 terminals. I have subsequently found that Ttk69 is required for normal accumulation of the Activin effector dSmad2 in R7 nuclei, suggesting that Ttk69 promotes Activin signaling to regulate R7 axon growth. Ttk69 appears to act through additional Activin-independent pathways as well, and research is ongoing to determine these pathways as well as the molecular mechanisms that govern axon growth and the transition to synapse formation. (2008) Neuregulin-mediated ErbB3 signaling is required for formation of zebrafish dorsal root ganglion neurons. vii ACKNOWLEDGMENTS First and foremost, I would like to thank my advisor, Tory, for her insight, guidance and patience, as well as for introducing me to the fine programming of Chicago Public Radio. I must also thank all members of the Herman lab …