Fragile X syndrome is the most common cause of inherited autism and results from loss of function of a single gene: FMR1. Most research into the pathogenesis of fragile X syndrome has focused on the role of FMRP, the protein encoded by FMR1, in neuronal health and function. However, recent work in cultured cells suggests that loss of FMR1 in astrocytes, star-shaped brain cells that help support neurons at their junctions (synapses), can contribute to the abnormal dendritic morphology and synapse development seen in fragile X. In addition, over the past decade, increasing evidence has demonstrated that glia — support cells in the brain — such as astrocytes play important roles in regulating neuronal synaptic development, plasticity and communication. These are activities that, if altered, may contribute to fragile X syndrome and autism.

Therefore, glia may represent a novel target for the development of therapies for fragile X syndrome. Mark Wu and his colleagues at Johns Hopkins University in Baltimore aim to use the fruit fly Drosophila melanogaster to test the hypothesis that FMR1 plays a role in glia, as well as in neurons, in regulating synaptic morphology and function in vivo. In addition, the researchers hope to use the fruit fly system to conduct large-scale screens to identify potential drug targets in glia that modulate fragile X phenotypes.

The fruit fly is a well-established model of fragile X syndrome that recapitulates a number of key features of the disease, including abnormal dendritic and synaptic morphology, increased neural excitability, altered circadian rhythms and sleep, and learning and memory defects. This work may point toward novel cellular and genetic mechanisms in the search for better treatments for fragile X syndrome.