Functional analysis of neurexin IV in Drosophila
Larry Zipursky, Ph.D.
University of California, Los Angeles
A number of the genes that have been implicated in autism have counterparts in model organisms, such as mice and fruit flies. This evolutionary conservation allows researchers to gain insights into the molecular pathways in which these autism-linked genes function. Lawrence Zipursky, of the University of California, Los Angeles, and his colleagues are studying one such conserved gene and its role in brain development.
The gene, called neurexin IV, is the fruit fly Drosophila melanogaster’s homolog of the human autism-linked gene CNTNAP2, and it is believed to play a role in regulating the formation of connections between neurons in the brain. Zipursky’s team plans to explore the gene’s role in the fruit fly’s visual system, which has proven to be a powerful model for uncovering new genes involved in human diseases — including cancer and neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases
Using the many tools available to manipulate genes in this well-studied model, the researchers will investigate the role of neurexin IV in various classes of neurons, such as those that sense light and those that relay visual information to the brain. The researchers will also analyze the functions of the handful of genes that have been shown to interact with neurexin IV. Together, these studies will provide a detailed picture of how neurexin IV regulates wiring in various types of neurons, and will set the stage for developing genetic screens to identify other components of the neurexin IV pathways.
Zipursky and colleagues hope to use the Drosophila model to shed light on how neurexin IV — and by extension, the human CNTNAP2 — functions during development, and to identify neurexin-interacting genes whose human counterparts could also contribute to autism.
Award #: 140366