Grant: Operating Grant

Animal behaviour is ultimately determined by the coordinated assembly of neurons into a complex and precise network of connections involving each other and their peripheral targets. Failure to assemble normal neural circuits during embryonic or childhood development can result in severe movement, behavioural, and/or learning deficits. Mechanisms that inhibit neurite growth play an essential role in sculpting neuronal connections by blocking inappropriate neurite formation, repelling growth cones during axon pathfinding, and terminating axon growth at target sites. We are interested in understanding these mechanisms using the anatomically simple nervous system of C. elegans as a model system. We have shown that VANG-1 and PRKL-1, core components of planar polarity signalling, specifically inhibit inappropriate neurite growth along directional vectors that are otherwise permissive for growth. To gain further insight into this process we propose to use genetic and biochemical approaches to understand how VANG-1 and PRKL-1 interact and to identify new pathway components. In the long term, we believe that factors that inhibit neurite growth may act as targets in new strategies to promote regeneration of axons damaged by neurodegenerative diseases, stroke or brain and spinal cord injury.