The Transcription Factor MEF2C Is Required for Craniofacial Development
Open accessAbstract
MEF2 transcription factors are well-established regulators of muscle development. We have discovered an unanticipated role for MEF2C in the neural crest, where tissue-specific inactivation results in neonatal lethality due to severe craniofacial defects. We show that MEF2C is required for expression of the Dlx5, Dlx6, and Hand2 transcription factor genes in the branchial arches, and we identify a branchial arch-specific enhancer in the Dlx5/6 locus, which is activated synergistically by MEF2C and Dlx5, demonstrating that these factors interact to induce transcription. Mef2c and Dlx5/6 also interact genetically. Mice heterozygous for either Dlx5/6 or Mef2c are normal at birth and survive to weaning. By contrast, heterozygosity for both Mef2c and Dlx5/6 results in defective palate development and neonatal lethality. Taken together, the studies presented here define a feed-forward transcriptional circuit between the MADS-box transcription factor MEF2C and the homeodomain transcription factors Dlx5 and Dlx6 in craniofacial development.
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MEF2C shows an excess of HF changes on the archaic lineage.
“another bone-related gene, MEF2C153, shows an excess of HF changes on the archaic lineage.”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [153]
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- Authors
- Verzi, M. P., Agarwal, P., Brown, C., McCulley, D. J., Schwarz, J. J., & Black, B. L.
- Affiliations
- University of California, San Francisco (US)
- Albany Medical Center Hospital (US)
- Corresponding author
- Black, Brian L.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 12
- Issue
- 4
- Pages
- 645-652
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC1920108
- OpenAlex
- W2121699212
- Cited by
- 129
- References
- 33
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 10
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2299 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research
- National Institutes of Health
- Howard Hughes Medical Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Cleft Lip and Palate Research
- Keywords
- MEF2C, craniofacial development, neural crest, Dlx5, Dlx6, Hand2, branchial arches, MADS-box transcription factors, homeodomain transcription factor, enhancer regulation, palate development, neonatal lethality, heterozygous mice
- MeSH terms
- Airway Obstruction, Animals, Base Sequence, Branchial Region, Enhancer Elements, Genetic, Face, Heterozygote, Molecular Sequence Data, Neural Crest, Skull, Transcription Factors, Transfection, Myogenic Regulatory Factors, Mice, Knockout, Gene Targeting, Homeodomain Proteins, NIH 3T3 Cells, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, MEF2 Transcription Factors
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