Rett syndrome (RTT) is a neurodevelopmental disorder that commonly involves autism. RTT is caused by mutations in a single gene, called MECP2. RTT is the only pervasive developmental disorder with a known genetic cause, and MECP2 mutations or expression defects are also observed in autism. Therefore, understanding the role of MECP2 in neurons has broad relevance to autism. Previous research has shown that MECP2's protein product (MeCP2) turns off other genes when they are no longer needed. This project seeks to understand how MeCP2 exerts its control, particularly on genes involved in neuronal maturation. Experiments will test the hypothesis that the form of MeCP2 and its location within the nucleus of a neuron influence which genes MeCP2 can shut down. What this means for people with autism: Understanding MeCP2 function in neurons will clarify the molecular interactions that go awry during neural development in RTT and autism. Because RTT shares significant overlap with autism, these results will also be instrumental in designing future therapies.