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MEF2C调节皮质抑制性和兴奋性突触以及与神经发育障碍相关的行为。

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

作者信息

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

机构信息

Department of Neurosciences, Medical University of South Carolina, Charleston, United States.

Department of Psychiatry, Harvard Medical School, Belmont, United States.

出版信息

Elife. 2016 Oct 25;5:e20059. doi: 10.7554/eLife.20059.

DOI:10.7554/eLife.20059
PMID:27779093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5094851/
Abstract

Numerous genetic variants associated with 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 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 mutant cortex identified a significant overlap with numerous synapse- and autism-linked genes, and the 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.

摘要

许多与[具体内容缺失]相关的基因变异与自闭症、智力障碍（ID）和精神分裂症（SCZ）有关——这是一组病理生理学尚不清楚的异质性神经发育障碍。MEF2C在发育中的皮质兴奋性神经元中高度表达，但其在这些神经元发育中的作用仍不清楚。我们在此表明，在皮质和海马兴奋性神经元（Emx1谱系）中条件性胚胎缺失[具体内容缺失]会导致体内皮质网络活动显著降低，部分原因是抑制性突触传递显著增加和兴奋性突触传递减少。此外，我们发现MEF2C主要作为一种细胞自主的转录抑制因子调节E/I突触密度。对[具体内容缺失]突变皮质中差异基因表达的分析确定了与许多突触和自闭症相关基因有显著重叠，并且[具体内容缺失]突变小鼠表现出许多让人联想到自闭症、ID和SCZ的行为，这表明扰乱新皮质中的MEF2C功能可在小鼠中产生自闭症样和ID样行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eadd/5094851/c273fe6112eb/elife-20059-fig7.jpg
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