Characterizing Wnt Signaling Pathways in Axon Guidance

Neural circuits are formed by directed growth of axons and dendrites and subsequent assembly of synapses between selected pre- and postsynaptic neurons at precise anatomical and subcellular locations. Although tremendous progress has been made in identifying the key axon guidance cues for nervous system development in the past two decades, the signaling and cell biological mechanisms of axon guidance still remain partially understood. The incomplete knowledge of how growth cones signal to respond to specific cues hinders our ability to apply the knowledge from axon guidance studies to repair circuits and restore function after traumatic injury and in neurodegenerative disorders. We found that Wnt family morphogens are axon guidance cues and the planar cell polarity pathway mediates Wnt function in axon guidance. We also found that Wnt signaling regulate axon regrow after spinal cord injury in adulthood and planar cell polarity signaling regulates the assembly of glutamatergic synapse formation. We plan to use Wnt/PCP signaling as a tool to address unsolved fundamental questions in growth cone guidance and understand its expanded role in adult axon regeneration. Aim 1: How PCP components create asymmetric signaling to mediate growth cone turning in development. Aim 2: Interactions between Wnt/PCP pathway and canonical Wnt pathway and the Shh pathway in A-P guidance. Aim 3: Role of Wnt/PCP signaling in functional recovery after spinal cord injury.