R7 PHOTORECEPTOR AXON TARGETING AND PRESYNAPTIC ASSEMBLY IN DROSOPHILA by SCOTT HOLBROOK A DISSERTATION

Original approval signatures are on file with the Graduate School and the University of Oregon Libraries. The development of a functional nervous system is paramount for the ability of animals to interact with their environments. Minor defects in nervous system function compromise the effectiveness of sensing and responding to stimuli. Severe defects in nervous system function often lead to extreme sensory, cognitive and motor skill impairment. The nervous system is a complex network of connections, with each neuron making functional contacts with several other neurons. Any single animal species generally exhibits a stereotyped pattern of neuronal connectivity, but the specific intrinsic and extrinsic signals that impart to a neuron its unique connective properties have only recently begun to be identified. In this study, we use the Drosophila visual system to examine neuronal connectivity. Our screen for genes involved in R7 photoreceptor connectivity led to the identification of the RhoGAP domain-containing protein dsyd-l and the transcriptional v repressor tramtrack. Flies harboring homozygous mutant dsyd-l R7s fail to phototax towards UV light, an innate behavior mediated by the R7s. Subsequent analysis ofaxons of dsyd-l R7s showed abnormal morphology in the region of presynaptic sites, suggesting that similar to its role in C. elegans, dsyd-l is involved in presynaptic assembly. Further analysis demonstrated a requirement for dsyd-l function in docking presynaptic components to terminal sites of contact. R7 axons are restricted to non-overlapping columns in the optic neuropil, thereby preserving spatial visual information in the retintopic map. The axon terminals of tramtrack mutant R7s exhibit overgrowth, similar to that observed in R7s that have loss of function mutations in genes involved in the activin signaling pathway. Previous studies have shown that activin signaling is involved in restricting R7 axons to their appropriate columns, and our results demonstrate that tramtrack may be functioning in the same pathway. One of two tramtrack isoforms, ttk69, is expressed in photoreceptors after they have differentiated, and expression of ttk69 is specifically required for R7 axon targeting. (2002) Drosophila HB9 is expressed in motoneurons and interneurons where it regulates gene expression and axon projections. (2001) Drosophila neuroblasts sequentially express transcription factors which specify the temporal identity of their neuronal progeny. Cell, 106, 511-521. The Drosophila PAR domain protein 1 (Pdp 1) gene encodes multiple differentially expressed mRNAs and proteins through the use of multiple enhancers and promoters. graduate school. She imparted to me a great deal of scientific knowledge, …