The majority of cases of autism spectrum disorders (ASDs) are thought to arise from multiple "hits," with many gene variants conferring a susceptibility to developing ASD. In rare cases, ASD appears to be linked to mutations in single genes which have particularly severe consequences for neural development. Analysis of the functional properties of single-gene mutations leading to autism is critical for understanding the shared cellular and molecular pathways onto which ASD-linked mutations converge. Recently, novel mutations in the gene encoding the neuronal protein Caspr2 were identified in a large group of ASD patients. Caspr2 appears similar to several other proteins linked to ASD, which are located at the cell surface and are involved in the formation and maintenance of synapses, the sites of communication between neurons. The proposed research will investigate the role of Caspr2 in neurodevelopment, using the mouse as a model system. Employing a variety of biochemical and cellular techniques, the predoctoral fellow will examine the effect of the ASD-linked mutations in Caspr2 on the development of the brain and its synapses. This study will further our understanding of how mutations in a single gene contribute to ASD, providing new insights into the causes of ASD and potential new therapeutic targets for the treatment of this disorder.