MEF2C regulates cortical inhibitory and excitatory synapses and behaviors relevant to neurodevelopmental disorders
Open accessAbstract
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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Animal models that mimic schizophrenia reproduce the loss of PV-INs in the hippocampus.
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From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [15]
Clear emergence of Sst, Vip and Id2 subtypes was apparent for a subset of cells at E18.5, but Pvalb neurons could not be clearly subdivided by P10.
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From Developmental diversification of cortical inhibitory interneurons (2018) · cites this paper as [28]
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- Authors
- Harrington, A. J., Raissi, A., Rajkovich, K., Berto, S., Kumar, J., Molinaro, G., Raduazzo, J., Guo, Y., Loerwald, K., Konopka, G., Huber, K. M., & Cowan, C. W.
- Affiliations
- Harvard University (US)
- The University of Texas Southwestern Medical Center (US)
- Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, United States
- Corresponding author
- Cowan, Christopher W
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-10-25
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5094851
- OpenAlex
- W2534955677
- Cited by
- 193
- References
- 72
- Citations by year
- 2026: 11 · 2025: 31 · 2024: 29 · 2023: 12 · 2022: 18 · 2021: 18 · 2020: 34 · 2019: 18 · 2018: 12 · 2017: 10
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (F32 HD078050, HD052731, OD010737, DA027664)
- Simons Foundation (SFARI #206919)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- MEF2C, neurodevelopmental disorders, autism spectrum disorder, intellectual disability, schizophrenia, excitatory neurons, inhibitory neurons, synaptic transmission, cortical network activity, transcriptional repression, hippocampus, differential gene expression, autism-like behavior
- MeSH terms
- Animals, Autistic Disorder, Behavior, Animal, Cerebral Cortex, Hippocampus, Intellectual Disability, Synapses, Mice, Gene Knockdown Techniques, MEF2 Transcription Factors, Neurodevelopmental Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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