Over the past decade, more than 100 candidate genes have been implicated in autism spectrum disorders. One of these genes, CNTNAP2, is ‘highly penetrant,’ meaning that its disruption is strongly correlated with autism. It is also evolutionarily conserved, so that its functions can be studied in model organisms such as the fruit fly. The fly homolog of CNTNAP2 is NRX-IV, which encodes the protein neurexin IV. Considerable progress has been made in understanding the role of this protein in forming junctions between epithelial cells, but little is known about how it functions in the developing central nervous system. Studies over the past 16 years suggest that it plays a role in mediating cell-cell interactions and the formation of synapses (neuronal junctions), which are functions relevant to autism spectrum disorders. Larry Zipursky and his colleagues at the University of California, Los Angeles, are seeking to understand the role of neurexin IV in the central nervous system and the consequences of mutations that alter its structure. After using genetic tools to selectively remove neurexin IV from subsets of developing neurons, they plan to assess defects in synapse formation and in the way neuronal projections, called axons, find their target cells. The researchers are aiming to identify proteins that interact with neurexin IV in order to characterize the pathways in which it functions. Four conserved mutations in CNTNAP2 are associated with autism; Zipursky’s team plans to engineer these mutations into the fly NRX-IV gene in order to assess the functional consequences. A detailed understanding of NRX-IV function and related pathway components may reveal how disruption of this pathway can lead to defects in brain development.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
