title: MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders.
abstract: Numerous genetic variants associated withMEF2Care 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 ofMef2cin 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 inMef2cmutant cortex identified a significant overlap with numerous synapse- and autism-linked genes, and theMef2cmutant 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.
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, United States.|Department of Psychiatry, Harvard Medical School, Belmont, United States.
authors: Adam J
authors: AJ
authors: Harrington
authors: Department of Psychiatry, Harvard Medical School, Belmont, United States.
authors: Aram
authors: A
authors: Raissi
authors: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States.
authors: Kacey
authors: K
authors: Rajkovich
authors: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States.
authors: Stefano
authors: S
authors: Berto
authors: Department of Psychiatry, Harvard Medical School, Belmont, United States.|Medical Scientist Training Program, The University of Texas Southwestern Medical Center, Dallas, United States.
authors: Jaswinder
authors: J
authors: Kumar
authors: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States.
authors: Gemma
authors: G
authors: Molinaro
authors: Department of Psychiatry, Harvard Medical School, Belmont, United States.
authors: Jonathan
authors: J
authors: Raduazzo
authors: Department of Psychiatry, Harvard Medical School, Belmont, United States.
authors: Yuhong
authors: Y
authors: Guo
authors: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States.
authors: Kris
authors: K
authors: Loerwald
authors: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States.
authors: Genevieve
authors: G
authors: Konopka
authors: Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States.
authors: Kimberly M
authors: KM
authors: Huber
authors: Department of Neurosciences, Medical University of South Carolina, Charleston, United States.|Department of Psychiatry, Harvard Medical School, Belmont, United States.
authors: Christopher W
authors: 0000-0001-5472-3296
authors: CW
authors: Cowan
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000196:embryology; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000196:embryology; D008607:Intellectual Disability / Q000503:physiopathology; D064326:MEF2 Transcription Factors / Q000378:metabolism; D051379:Mice; D065886:Neurodevelopmental Disorders / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*
chemical_list: D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse
keywords: mouse; neurodevelopmental disorder; neuron; neuroscience; synapse; transcription factors