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UBC Theses and Dissertations

Axon guidance genes are essential in the adult nervous system Vaikakkara Chithran, Aarya


Axon guidance cues are extracellular signals that direct the growth and steering of neuronal growth cones. Both attractive and repulsive cues are required to guide developing axons to their targets. Nonetheless, after axons have reached their targets and established functional circuits, many neurons continue to express these developmental cues. The expression of these genes in the adult indicates that there are likely additional roles for guidance cues beyond the initial phase of neuronal process outgrowth, growth cone navigation, and target innervation. The central goal of my work is to determine the functions of these cues in the mature nervous system. I hypothesize that axon guidance genes expressed in the adult nervous system have functional roles in the maintenance of neural circuits. Work in the past few decades has led to the discovery of numerous axon guidance genes and identified their functions during development. This study is the first to perform an RNA-mediated interference (RNAi) screen for axon guidance genes that have functional roles in the mature nervous system. Axon guidance genes expressed in the adult Drosophila melanogaster nervous system were identified using bio-informatics tools. In Drosophila, more than 96% of embryonic cues continue to be expressed in the adult. The axon guidance genes were knocked down in adult neurons using RNAi via spatial and temporal control of GAL4-UAS system. I have identified 15 axon guidance genes that are essential for survival and normal behavior (climbing, mobility, activity/rest cycle) in adult Drosophila. The results suggests that axon guidance genes are functional in the adult nervous system and may be involved in the maintenance of neural circuits underlying these phenotypes. Further studies on circuit morphology are required to understand better how axon guidance genes contribute to the maintenance of neuronal structure in adult brains.

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