Project 467071

The cerebellum is a structure located at the back of the brain and it regulates the integration and processing of sensory and motor information. Structurally, the cerebellum is relatively simple, comprised of three distinct cell layers, each populated with unique cell types. While its organization is relatively simple, the cerebellum maintains a large degree of functional complexity due to its dense cellular packing and extensive network of connections. For instance, while accounting for ~10% of the brains mass, the cerebellum contains ~80% of the neurons in the brain. The generation of this dense anatomical organization requires careful control of developmental processes to ensure the proper migration and positioning of cells, many of which remain undiscovered. For cells to get from their birthplace to their destination they rely on the cytoskeleton, which acts as a set of molecular train tracks to get the cargo (cells) to their destination (respective cerebellar layer). When cells are displaced from their appropriate destination due to disruptions in cytoskeletal elements, developmental disorders may arise, as seen in patients with autism spectrum disorder (ASD) as well as in cases of medulloblastoma, the most common cancerous brain tumor in children. Thus, it is extremely important to gain a better understanding of the various mechanisms by which these migratory cells in the cerebellum achieve their proper positioning and allow for such complex neuronal circuitry to form. For the proposed study, I will investigate the role of a novel neural-specific cytoskeletal regulator in the formation of the cerebellum. The results obtained from this study will provide insight into the molecular and cellular mechanisms underlying neurodevelopmental disorders of the cerebellum.