title: Combinatorial control of Drosophila mef2 gene expression in cardiac and somatic muscle cell lineages.
abstract: The Drosophila mef2 gene encodes a MADS domain transcription factor required for the differentiation of cardiac, somatic, and visceral muscles during embryogenesis and the patterning of adult indirect flight muscles assembled during metamorphosis. A prerequisite for D-MEF2 function in myogenesis is its precise expression in multiple cell types during development. Novel enhancers for D-mef2 transcription in cardiac and adult muscle precursor cells have been identified and their regulation by the Tinman and Twist myogenic factors have been demonstrated. However, these results suggested the existence of additional regulators and provided limited information on the specification of progenitor cells for different muscle lineages. We have further characterized the heart enhancer and show it is part of a complex regulatory region controlling the activation and repression of D-mef2 transcription in several cell types. The mutation of a GATA sequence in the enhancer changes its specificity from cardial to pericardial cells. Also, the addition of flanking sequences to the heart enhancer results in expression in a new cell type, that being the founder cells of a subset of body wall muscles. As tinman function is required for D-mef2 expression in both the cardial and founder cells, these results define a shared regulatory DNA that functions in distinct lineages due to the combinatorial activity of Tinman and other factors that work through adjacent sequences. The analysis of D-mef2-lacZ fusion genes in mutant embryos revealed that the specification of the muscle precursor cells involved the wingless gene and the activation of a receptor tyrosine kinase signaling pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: K
authors.initials: K
authors.lastname: Gajewski
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: C Y
authors.initials: CY
authors.lastname: Choi
authors.forename: R A
authors.initials: RA
authors.lastname: Schulz
mesh_terms: D000818:Animals; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006321:Heart / Q000196:embryology; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology; D064326:MEF2 Transcription Factors; D008648:Mesoderm; D009132:Muscles / Q000196:embryology; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D051879:Twist-Related Protein 1; D051155:Wnt1 Protein
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D064326:MEF2 Transcription Factors; C499409:Mef2 protein, Drosophila; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; D051155:Wnt1 Protein; C106185:engrailed homeobox proteins; C102933:tin protein, Drosophila; C074622:wg protein, Drosophila