Emerging roles for MEF2 in brain development and mental disorders
Open accessAbstract
The MEF2 family of transcription factors regulate large programs of gene expression important for the development and maintenance of many tissues, including the brain. MEF2 proteins are regulated by neuronal synaptic activity, and they recruit several epigenetic enzymes to influence chromatin structure and gene expression during development and throughout adulthood. Here, we provide a brief review of the recent literature reporting important roles for MEF2 during early brain development and function, and we highlight emerging roles for MEF2 as a risk factor for multiple neurodevelopmental disorders and mental illnesses, such as autism, intellectual disability, and schizophrenia.
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MEF2C exerts anti-inflammatory effects within the brain by suppressing the expression of proinflammatory cytokines and protecting neurons from inflammatory damage.
“MEF2C exerts anti‐inflammatory effects within the brain by suppressing the expression of proinflammatory cytokines and protecting neurons from inflammatory damage.”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [43]
The References section cites a study titled “Mef2C restrains microglial inflammatory response,” supporting a brain anti-inflammatory role for MEF2C. Neither that entry nor the review’s Conclusion specifies suppression of proinflammatory cytokines or protection of neurons from inflammatory damage; the Conclusion says MEF2’s role in microglia is only beginning to be explored. The indexed passages provide no page numbers. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMEF2C is a transcription factor with crucial roles in immune regulation, synaptic plasticity, and neuronal survival.
“MEF2C is a transcription factor with crucial roles in immune regulation, synaptic plasticity, and neuronal survival [43, 44].”
From Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease (2026) · cites this paper as [43]
The DLX5/6-N-Haplotype includes enhancers (I56i, I56ii, and MEF2) capable to direct DLX5/6 expression in the brain.
“The DLX5/6-N-Haplotype includes enhancers (I56i, I56ii, and MEF2) capable to direct DLX5/6 expression in the brain (Fazel Darbandi, et al. 2016; Assali, et al. 2019).”
From <i>DLX5/6</i> GABAergic Expression Affects Social Vocalization: Implications for Human Evolution (2021) · cites this paper as Assali, et al. 2019
The Introduction describes MEF2 proteins as transcription factors that bind DNA and regulate gene expression, but it does not connect them to DLX5/6. Searches for the DLX5/6-N-haplotype, I56i, I56ii, and DLX5/6 expression found no passage addressing whether those enhancers direct DLX5/6 expression in the brain. (LLM, conf=0.74)
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Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease
Kim, B., Wang, S. S., Kim, J. R., & Kim, J. (2026) · BioEssays · doi:10.1002/bies.70186
“MEF2C is a transcription factor with crucial roles in immune regulation, synaptic plasticity, and neuronal survival [43, 44].”
Severe neurodevelopmental disorder caused by an MEF2C nonsense mutation
Morisada, N., Ishida, Y., Tokumoto, S., Maruyama, A., & Iijima, K. (2021) · Pediatrics International · doi:10.1111/ped.14647
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Additional file 7 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160927
Additional file 6 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160924
Additional file 5 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160921
Additional file 8 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160930
Fat matters for natural killer cell activity
Wong, P., & Fehniger, T. A. (2024) · Nature Immunology · doi:10.1038/s41590-024-01825-w
TrkB-dependent antidepressants action involves Dlx5/6 inhibition in cortical GABAergic neurons.Preprint
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Roles for the MEF2 Transcription Factors in Synapse and Circuit Development and Plasticity
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MEF2C is a potential prognostic biomarker for osteosarcoma
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A calcium-sensing MCTP1/FYN/MEF2C circuit drives therapy-induced neuroendocrine prostate cancer
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Additional file 1 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160909
Additional file 4 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160918
Additional file 10 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160897
Additional file 11 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160900
Additional file 3 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160915
Additional file 2 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160912
Additional file 9 of Trem2 Y38C mutation and loss of Trem2 impairs neuronal synapses in adult mice
Jadhav, V., Lin, P. B., Pennington, T., Prisco, G. V. D., Jannu, A. J., Xu, G., Moutinho, M., Zhang, J., Atwood, B. K., Puntambekar, S. S., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13160933
An Integrative Single-Cell Epigenomic Atlas Annotates the Regulatory Genome of the Adult Mouse BrainPreprint
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- Authors
- Assali, A., Harrington, A. J., & Cowan, C. W.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Cowan, Christopher W
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2019-12
- Volume
- 59
- Pages
- 49-58
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC6874740
- OpenAlex
- W2947078402
- Cited by
- 92
- References
- 109
- Citations by year
- 2026: 9 · 2025: 23 · 2024: 19 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 14 · 2019: 2
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- MEF2 transcription factors, brain development, neurodevelopmental disorders, autism spectrum disorder, intellectual disability, schizophrenia, synaptic activity, epigenetic regulation, chromatin structure, gene expression regulation, mental illness risk
- MeSH terms
- Autistic Disorder, Brain, Humans, Neurons, Gene Expression Regulation, Developmental, MEF2 Transcription Factors
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