Understanding the Function of Tuberous Sclerosis Complex Genes in Neural Development: Roles in Synapse Assembly and Axon Guidance

摘要

The goal of our project was to use the fruitfly Drosophila melanogaster, to identify molecular mechanisms affecting nervous system development and behavior that occur as a consequence of Tsc-Tor-Rheb signaling disruption, mimicking the types of changes that are known to occur in human patients with tuberous sclerosis. In our first manuscript we established that hyperactivity of the Tor pathway had several important neurodevelopmental consequences, including misrouting of axon guidance in the visual system and synapse overgrowth at the neuromuscular junction. We showed that synapse overgrowth mediated by Rheb was insensitive to rapamycin, a Tor Complex 1 inhibitor, suggesting that other Torcontaining complexes mediate these changes in synapse function.