Role of Rho GTPase signalling pathways in neuronal morphogenesis. (360G-Wellcome-078045_Z_05_Z)

Cytoskeletal regulation leading to cell shape changes are crucial during cell division, motility and morphogenesis. My aim is to understand how signalling pathways regulate the cytoskeleton to elicit neuronal morphogenesis. My recent work has shown that Rho GTPases are key intracellular regulators of axon growth, guidance and branching and that different pathways are involved in these processes. Part of this proposal will build on key preliminary observations on the roles PI3K/Akt, JNK and cytoskeletal regulated pathways may play in neuronal morphogenesis. As cells require multiple signals to elicit appropriate responses, the goal is to not only characterise how distinct intracellular pathways are involved but also to elucidate how multiple pathways are integrated during morphogenesis. Numerous evidences reveal that nerve growth cones pathfind by integrating multiple extracellular cues and I have found that neurons in the Drosophila brain act similarly. I am currently characterising some novel cues, not previously shown to be involved in Drosophila axon guidance and I plan to elucidate how these cues signal to the cytoskeleton. I am using Drosophila as many neurodevelopmental mechanisms are conserved between flies and mammals and many genetic tools (see Q18) are available to rigorously test hypotheses on the mechanisms of neuronal morphogenesis.