title: A series of mutations in the D-MEF2 transcription factor reveal multiple functions in larval and adult myogenesis in Drosophila.
abstract: The D-mef2 gene encodes a MADS domain transcription factor expressed in differentiated muscles and their precursors in the Drosophila embryo. Embryos deficient for D-MEF2 protein due to a deletion of upstream transcriptional control sequences fail to form muscle, suggesting that the gene is required for muscle cell differentiation. To directly demonstrate a role for D-mef2 in embryonic myogenesis, we isolated gene mutants containing EMS-induced point mutations, characterized the effects of these mutations on D-MEF2 protein stability and nuclear localization, and analyzed the resulting muscle phenotypes. Our results show that in the somatic muscle lineage, D-mef2 is required for both the formation and patterning of body wall muscle. In the absence of somatic myogenesis, there is extensive apoptosis among the myoblast cell population. In contrast, in the cardiac muscle lineage, morphogenesis of the dorsal vessel occurs normally but the three myosin subunit genes are not expressed. Mutant embryos also exhibit an abnormal midgut morphology, which correlates with the absence of alpha PS2 integrin gene expression and muscle-specific enhancer function, suggesting that D-mef2 regulates the inflated locus which encodes this integrin subunit. D-MEF2 is also expressed in adepithelial cells and rare D-mef2 transheterozygous mutant adults fail to fly, consistent with defects observed in the indirect flight muscles. These results demonstrate that the D-mef2 gene has multiple functions in myogenesis and tissue morphogenesis during Drosophila development.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: G
authors.initials: G
authors.lastname: Ranganayakulu
authors.forename: B
authors.initials: B
authors.lastname: Zhao
authors.forename: A
authors.initials: A
authors.lastname: Dokidis
authors.forename: J D
authors.initials: JD
authors.lastname: Molkentin
authors.forename: E N
authors.initials: EN
authors.lastname: Olson
authors.forename: R A
authors.initials: RA
authors.lastname: Schulz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D016023:Integrins / Q000235:genetics; D064326:MEF2 Transcription Factors; D008297:Male; D008969:Molecular Sequence Data; D024510:Muscle Development; D009132:Muscles / Q000196:embryology*; D018006:Myogenic Regulatory Factors; D009218:Myosins / Q000235:genetics; D010641:Phenotype; D017354:Point Mutation; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D016023:Integrins; D064326:MEF2 Transcription Factors; C499409:Mef2 protein, Drosophila; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors; D009218:Myosins