Investigating WNT signaling variants in mouse models of autism

Benjamin Cheyette and his colleagues at the University of California, San Francisco have discovered several variations in the sequence of the DIXDC1 gene in individuals with autism, using DNA obtained from the Simons Simplex Collection. DIXDC1 encodes a protein involved in communication between neurons during development. This cell communication pathway, known as the WNT signaling pathway, has been implicated in autism by sequence findings involving other genes, such as CHD8.

In preliminary experiments, Cheyette and his team found that sequence variants in DIXDC1 alter the efficiency of this protein in activating WNT signaling, and that disruption of DIXDC1 in cultured neurons affects the formation of synapses, or connections between neurons. They also found that disruption of this gene in mice affects behavior.

Cheyette and his group aim to pursue these findings by testing whether the sequence variations found in individuals with autism similarly affect synapse development in cultured neurons, and whether mice with DIXDC1 disruption have similar developmental effects in their neurons.