title: The Drosophila Transcription Factors Tinman and Pannier Activate and Collaborate with Myocyte Enhancer Factor-2 to Promote Heart Cell Fate.
abstract: Expression of the MADS domain transcription factor Myocyte Enhancer Factor 2 (MEF2) is regulated by numerous and overlapping enhancers which tightly control its transcription in the mesoderm. To understand how Mef2 expression is controlled in the heart, we identified a late stage Mef2 cardiac enhancer that is active in all heart cells beginning at stage 14 of embryonic development. This enhancer is regulated by the NK-homeodomain transcription factor Tinman, and the GATA transcription factor Pannier through both direct and indirect interactions with the enhancer. Since Tinman, Pannier and MEF2 are evolutionarily conserved from Drosophila to vertebrates, and since their vertebrate homologs can convert mouse fibroblast cells to cardiomyocytes in different activator cocktails, we tested whether over-expression of these three factors in vivo could ectopically activate known cardiac marker genes. We found that mesodermal over-expression of Tinman and Pannier resulted in approximately 20% of embryos with ectopic Hand and Sulphonylurea receptor (Sur) expression. By adding MEF2 alongside Tinman and Pannier, a dramatic expansion in the expression of Hand and Sur was observed in almost all embryos analyzed. Two additional cardiac markers were also expanded in their expression. Our results demonstrate the ability to initiate ectopic cardiac fate in vivo by the combination of only three members of the conserved Drosophila cardiac transcription network, and provide an opportunity for this genetic model system to be used to dissect the mechanisms of cardiac specification.
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131-1091, United States of America.
authors.forename: TyAnna L
authors.initials: TL
authors.lastname: Lovato
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131-1091, United States of America.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Sensibaugh
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131-1091, United States of America.
authors.forename: Kirstie L
authors.initials: KL
authors.lastname: Swingle
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131-1091, United States of America.
authors.forename: Melody M
authors.initials: MM
authors.lastname: Martinez
authors.affiliation: Department of Biology, University of New Mexico, Albuquerque, NM 87131-1091, United States of America.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Cripps
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D016384:Consensus Sequence; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006321:Heart / Q000196:embryology; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D064233:Sulfonylurea Receptors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D018006:Myogenic Regulatory Factors; D012097:Repressor Proteins; D064233:Sulfonylurea Receptors; D015534:Trans-Activators; D014157:Transcription Factors; C475488:Hand protein, Drosophila; C499409:Mef2 protein, Drosophila; C109259:pnr protein, Drosophila; C577513:sulfonylurea receptor, Drosophila; C102933:tin protein, Drosophila