Mechanisms that control neuronal microtubule polarity

Project Summary / Abstract Microtubules are critical cellular infrastructure that help neurons survive over long time frames and after injury. In response to axon injury, microtubule nucleation is upregulated and this is important for resilience to additional stress. Past efforts have focused on the mechanism that upregulates microtubule dynamics in dendrites after axon injury. However, microtubule dynamics are also upregulated in the part of the axon that remains. It is not known whether the same pathway is responsible for the injury response in axons and so this will be focus of the current work. A MicroPoint laser is essential for performing controlled axon injury to investigate mechanisms that change microtubule behavior in the axon. While it has already been established that axon injury upregulates microtubule dynamics as part of a resilience response, a new hypothesis about this response will also be tested. The new hypothesis is that damage to surrounding cells could also trigger increased microtubule dynamics and neuroprotection in their neuronal neighbors. This hypothesis is based on the finding that the epithelial support cells secrete Wnt ligands to regulate microtubule dynamics in neurons. To test the hypothesis, epithelial cells will be injured and microtubule dynamics in nearby neurons will be measures. Pilot experiments have been performed, and a MicroPoint laser used at high power can damage epithelial cells. By pairing neuronal injury with live cell imaging assays, the role of microtubule dynamics in neuronal health and resilience will be eludicated.