This is a Clinical Investigator Award, providing a medical investigator with an opportunity to develop into an independent researcher. Understanding the etiology of autism is important for improving clinical treatments and diagnostic testing, as well as for understanding human neurodevelopment. The Fox-1 gene (also called A2BP1) may be involved in neurodevelopment and has also been linked to autism in a few patients. Fox-1 is a neuron-specific regulator of alternative gene splicing that appears to play a significant role in gene expression in both human and mouse brain. This research will identify genes whose alternative splicing is regulated by Fox-1 in human neuronal cells using a splicing microarray platform and identify Fox-1-dependent alternative splicing changes that occur during the differentiation of human neuronal cells to neurons. The role of these Fox-1 target genes in neurodevelopment will also be characterized in humans and mice. The studies proposed here, examining the role a brain-specific regulator of gene expression in neurodevelopment, will extend knowledge of what can cause ASD and may ultimately help to better treat, prevent, or someday even cure autism.