While it is clear that there is a strong genetic contribution to the cause of autism spectrum disorders (ASD), classical genetic mapping techniques have yet to yield a robust model for ASD. Meanwhile, studies of Tuberous Sclerosis Complex (TSC) can provide clues to autism's etiology because 50% of TSC patients are diagnosed with autism and because the genetic causes of TSC are known. TSC stems from mutations in one of two genes (TSC1 or TSC2) and in mouse models of TSC, Dr. Sahin's lab has found aberrant axon growth, targeting and myelination in the brain, which would result in miswiring between neurons. This fits with the growing evidence for disrupted neuronal connectivity in autism. In this research project Dr. Sahin's post-doctoral fellow will investigate how TSC1/2 gene products regulate axon guidance, myelination and circuit formation in the brain. Specifically, the molecular mechanisms of axon guidance, which involves interactions between TSC proteins and Eph receptors, will be analyzed. The study will also characterize the effect TSC1/2 expression has on the myelin-making cells (“oligodendrocytes”). Finally, the study will investigate the full complement of axonal proteins whose expression is controlled by TSC1/2. What this means for people with autism:This study will elucidate the cellular and molecular mechanisms behind the disrupted connectivity in the brain in autism, and potentially identify molecules that can serve as targets for new therapies.