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Role of a novel pathway in autism spectrum disorders

Louis Reichardt, Ph.D.
University of California, San Francisco

Many symptoms of autism, such as social impairments and repetitive behaviors, are accompanied by abnormal brain activity in the forebrain region. Louis Reichardt and his colleagues at the University of California, San Francisco studied the development of the forebrain, focusing on an important intercellular signaling pathway known as the Wnt pathway.

In particular, Reichardt’s team studied a Wnt-regulated signaling pathway that includes the proteins Disheveled, DACT1, p120-catenin and delta-catenin. This protein pathway controls the rearrangement of a cell's cytoskeleton and the activity of cell adhesion proteins that connect one cell to another. These two processes help form synapses, the specialized sites of communication between neurons.

The researchers evaluated how the behavior of mice depends upon Wnt pathway activity in the forebrain, specifically looking for autism-like behaviors that result from its disruption. They observed deficits in social behavior in mice lacking proteins in this pathway.

They found that p120-catenin and delta-catenin help organize synapses and appear to be important for the stability of synapses throughout life. In their absence, synapses form and function abnormally.

Interestingly, mutations in the human delta-catenin gene may be associated with some cases of autism, and rare mutations in the human N-cadherin gene, whose protein product is regulated by p120-catenin and delta-catenin, are associated with obsessive-compulsive disorder1. Reichardt’s work to determine which mechanisms account for the autism-like behaviors in mouse models may suggest new ways to diagnose and treat the disorder in people.

References:

1. Moya P.R. et al. Eur. J. Hum. Genet. Epub ahead of print (2013) PubMed


proposalCENTRAL #137394