Function of a Gene Linked to Autism

Image of a fluorescently labeled mossy fiber synapse from a mouse brain.

Genetic studies have linked autism in humans to dysregulation of synaptic function and altered neural connectivity. Kirrel3 is a key but unstudied autism susceptibility gene. Williams and colleagues discovered that the Kirrel3 gene is necessary to form one part of a massive synaptic complex called the mossy fiber synapse. Kirrel3 is responsible for forming the part of the synapse that turns on inhibitory neurons.

These synapses govern the balance of neuronal activity in the hippocampus, a structure critical for learning and memory. Therefore, without proper Kirrel3 function, the balance of neuronal activity is tipped such that hippocampal neurons are overactive. This work is the first insight into the function of this important disease gene. The Williams lab continues to focus on understanding how specific mutations in Kirrel3 found in patients with autism and intellectual disabilities alter Kirrel3’s function in the brain.

References:

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The intellectual disability gene Kirrel3 regulates target-specific mossy fiber synapse development in the hippocampus. Martin EA, Muralidhar S, Wang Z, Cervantes DC, Basu R, Taylor MR, Hunter J, Cutforth T, Wilke SA, Ghosh A, Williams ME. Elife. 2015 Nov 17;4:e09395.

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Examining hippocampal mossy fiber synapses by 3D electron microscopy in wildtype and Kirrel3 knockout mice. Martin EA, Woodruff D, Rawson RL, Williams ME. eNeuro. 2017 May-Jun;4(3:ENEURO.0088-17.2017.

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