The role of MAST3 in neurodevelopment and disease (21372)
The development of the human brain occurs early in human life and requires the coordination of key cellular events, including the generation, migration and differentiation of neurons. Genetic mutations that perturb these processes cause neurodevelopmental disorders, such as microcephaly, epilepsy, or autism spectrum disorders. Recent genetic studies have implicated MAST3 (microtubule-associated serine/threonine kinase 3) in a range of neurological conditions; however, the underlying molecular and cellular mechanisms are unknown. In this PhD project, I aim to remedy this deficit. To this end I have three goals. To: (1) Generate novel MAST3 mouse models that recapitulate disease causing mutations; (2) Undertake behavioral and anatomical characterization of these mouse lines; and (3) Generate MAST3-disease related phenotypes in vitro using stem cell models and cerebral organoids, and further characterize them morphologically and cellullary. Collectively, my doctorate will shed light on how MAST3 contributes to neurodevelopment and will provide insight into the pathophysiological mechanisms associated with MAST3 mutations.