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Roles of Wnt Signaling/Scaffolding Molecules in Autism

San Francisco
State/Province Full: 
United States

Autism spectrum disorders (ASDs) are thought to arise from disruptions in brain development. A crucial biochemical pathway involved in neurodevelopment is the Wnt signaling pathway, which can affect both brain size and organization. Misregulation of Wnt signaling is therefore a potential cause of ASDs, and mutations in genes that affect the Wnt pathway might confer a risk of ASDs. Recently, a family was discovered in which two children diagnosed with ASD harbored a mutation in the Dact1 gene, which is involved in Wnt signaling. The present study will investigate the effects of Dact1 in brain development, using the mouse as a model system. Mice genetically engineered to lack Dact1 will be used to examine the development of neurons and neuronal connections in the absence of this gene. The predoctoral fellow will test the hypothesis that loss of Dact1 causes a decreased number of synapses, or connections between neurons. He will also investigate the consequences of the particular Dact1 mutation found in autistic patients on neuronal development and function. Determining how Dact1 affects neural development may provide an important clue towards understanding the biochemical processes involved in ASDs.