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| Status |
Public on Sep 23, 2016 |
| Title |
MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
We carried out RNA-sequencing (RNA-seq) of somatosensory cortical tissue from control (Mef2cfl/fl) or Mef2c cKO (Mef2cfl/fl; Emx1-Cre) adult male mice. For the RNA-seq, three indipendent replicates were used for the mouse tissues.
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| Contributor(s) |
Harrington AJ, Raissi A, Berto S, Molinaro G, Konopka G, Cowan CW |
| Citation(s) |
27779093 |
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| Submission date |
Sep 22, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Christopher W Cowan |
| E-mail(s) |
cowanc@musc.edu
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| Phone |
8437922935
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| Organization name |
Medical University of South Carolina
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| Department |
Neurosiences; Psychiatry
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| Street address |
173 Ashley Ave, BSB 403
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| City |
Charleston |
| State/province |
SC |
| ZIP/Postal code |
29425 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA343877 |
| SRA |
SRP090281 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE87202_RAW.tar |
980.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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