Many of the symptoms of autism, such as social impairments and repetitive behaviors, are accompanied by abnormal brain activity in the forebrain region. Dr. Reichardt and his colleagues plan to study the development of the forebrain, focusing on an important intercellular signaling pathway known as the Wnt pathway. The Wnt pathway has been implicated in synapse formation in the forebrain, in regions such as the hippocampus and in the neocortex. One target of the Wnt pathway, a cell adhesion protein called p120 catenin, is stabilized by Wnt signaling and moves to synapses as they are forming and organizes the underlying cytoskeleton. Research indicates that the neurons of the hippocampus develop fewer synapses when they lack p120 catenin. More recently, they reported that the absence of p120 catenin impairs the localization of synaptic vesicles at synapses and reduces synaptic transmission. Reichardt proposes that disruption of the Wnt pathway prevents p120 catenin from building synapses in the forebrain, disabling the motor, memory, and emotional pathways encoded there and potentially causing autism. He and his team plan to collaborate with three other research groups to study the interactions between p120 catenin and the Wnt pathway in the forebrain and to determine whether defects in this pathway could lead to autism. The researchers plan to analyze how several key components of the Wnt pathway influence synapse formation and the shape of the neurons, which would affect how well the cells communicate to control movements and social interactions. Reichardt and colleagues then plan to evaluate how the behavior of the mice depends on this Wnt pathway activity in the forebrain, specifically looking for autism-like behaviors that result from disrupting the Wnt-p120 catenin pathway.