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PMID:17420000

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Citation

Verzi, MP, Agarwal, P, Brown, C, McCulley, DJ, Schwarz, JJ and Black, BL (2007) The transcription factor MEF2C is required for craniofacial development. Dev. Cell 12:645-52

Abstract

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.

Links

PubMed PMC1920108 Online version:10.1016/j.devcel.2007.03.007

Keywords

Airway Obstruction/embryology; Airway Obstruction/mortality; Animals; Base Sequence; Basic Helix-Loop-Helix Transcription Factors/metabolism; Branchial Region/metabolism; Enhancer Elements, Genetic; Face/embryology; Gene Targeting; Heterozygote; Homeodomain Proteins/genetics; Homeodomain Proteins/metabolism; Mice; Mice, Knockout; Molecular Sequence Data; Myogenic Regulatory Factors/genetics; Myogenic Regulatory Factors/metabolism; Myogenic Regulatory Factors/physiology; NIH 3T3 Cells; Neural Crest/metabolism; Skull/embryology; Skull/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:DLX5

acts_upstream_of_or_within

GO:0060021: roof of mouth development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101927
MGI:MGI:99458

P

  • results_in_development_of:(EMAPA:18948)

Seeded From UniProt

complete

MOUSE:DLX5

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:99458

P

  • has_input:(MGI:MGI:101927)|has_input:(MGI:MGI:101926)

Seeded From UniProt

complete

MOUSE:DLX6

acts_upstream_of_or_within

GO:0060021: roof of mouth development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101926
MGI:MGI:99458

P

  • results_in_development_of:(EMAPA:18948)|results_in_development_of:(EMAPA:18948)|results_in_development_of:(EMAPA:18948)

Seeded From UniProt

complete

MOUSE:MEF2C

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:101926)|has_input:(MGI:MGI:101927)

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0048704: embryonic skeletal system morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3603182

P

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0048703: embryonic viscerocranium morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3603182

P

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0060536: cartilage morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3603182

P

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0060021: roof of mouth development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101926
MGI:MGI:101927

P

  • results_in_development_of:(EMAPA:18948)

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101926

P

  • has_input:(MGI:MGI:101925)|has_input:(MGI:MGI:101927)

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0060536: cartilage morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3603182

P

has_participant:(EMAPA:17907)

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0060021: roof of mouth development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101926
MGI:MGI:101927

P

results_in_development_of:(EMAPA:18948)

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0048704: embryonic skeletal system morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3603182

P

has_participant:(EMAPA:18290)|has_participant:(EMAPA:17928)

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0048703: embryonic viscerocranium morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3603182

P

has_participant:(EMAPA:36570)|has_participant:(EMAPA:17682)

Seeded From UniProt

complete

MOUSE:MEF2C

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101926

P

has_regulation_target:(MGI:MGI:101925)|has_regulation_target:(MGI:MGI:101927)

Seeded From UniProt

complete

MOUSE:MEF2C

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

has_regulation_target:(MGI:MGI:101926)|has_regulation_target:(MGI:MGI:101927)

Seeded From UniProt

complete


See also

References

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