MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders

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MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders

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Title: MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders
Author: Harrington, Adam J; Raissi, Aram; Rajkovich, Kacey; Berto, Stefano; Kumar, Jaswinder; Molinaro, Gemma; Raduazzo, Jonathan; Guo, Yuhong; Loerwald, Kris; Konopka, Genevieve; Huber, Kimberly M; Cowan, Christopher W

Note: Order does not necessarily reflect citation order of authors.

Citation: Harrington, A. J., A. Raissi, K. Rajkovich, S. Berto, J. Kumar, G. Molinaro, J. Raduazzo, et al. 2016. “MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders.” eLife 5 (1): e20059. doi:10.7554/eLife.20059. http://dx.doi.org/10.7554/eLife.20059.
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Abstract: Numerous genetic variants associated with MEF2C are linked to autism, intellectual disability (ID) and schizophrenia (SCZ) – a heterogeneous collection of neurodevelopmental disorders with unclear pathophysiology. MEF2C is highly expressed in developing cortical excitatory neurons, but its role in their development remains unclear. We show here that conditional embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons (Emx1-lineage) produces a dramatic reduction in cortical network activity in vivo, due in part to a dramatic increase in inhibitory and a decrease in excitatory synaptic transmission. In addition, we find that MEF2C regulates E/I synapse density predominantly as a cell-autonomous, transcriptional repressor. Analysis of differential gene expression in Mef2c mutant cortex identified a significant overlap with numerous synapse- and autism-linked genes, and the Mef2c mutant mice displayed numerous behaviors reminiscent of autism, ID and SCZ, suggesting that perturbing MEF2C function in neocortex can produce autistic- and ID-like behaviors in mice. DOI: http://dx.doi.org/10.7554/eLife.20059.001
Published Version: doi:10.7554/eLife.20059
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094851/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626123
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