Pinpointing the specific molecular defects that cause autism is a key approach to developing appropriate treatments for the disorder. One way to uncover a disrupted molecular pathway is by identifying single-gene mutations that are associated with the disease, as has been done in Alzheimer's and Parkinson's. Littleton and his colleagues are applying the same approach to autism. The researchers are examining one pathway in particular — synapses — which is likely to be disrupted by at least one single-gene mutation carried by people with autism. Using a fruit fly model, the Littleton laboratory has shown that regulation of endosomes — enclosed 'sacs' that transport proteins within the cell — is crucial to synaptic development and flexibility. Littleton's group will use the well-established fruit fly model to examine whether — and if so, how — mutations in the NHE9 gene, which is mutated in some people with autism, disrupt endosomal function and thus prevent adequate transport of growth-promoting factors to synapses during neuronal development.