title: The bHLH Transcription Factor Hand Regulates the Expression of Genes Critical to Heart and Muscle Function in Drosophila melanogaster.
abstract: Hand proteins belong to the highly conserved family of basic Helix-Loop-Helix transcription factors and are critical to distinct developmental processes, including cardiogenesis and neurogenesis in vertebrates. In Drosophila melanogaster a single orthologous hand gene is expressed with absence of the respective protein causing semilethality during early larval instars. Surviving adult animals suffer from shortened lifespan associated with a disorganized myofibrillar structure being apparent in the dorsal vessel, the wing hearts and in midgut tissue. Based on these data, the major biological significance of Hand seems to be related to muscle development, maintenance or function; however, up to now the physiological basis for Hand functionality remains elusive. Thus, the identification of genes whose expression is, directly or indirectly, regulated by Hand has considerable relevance with respect to understanding its biological functionality in flies and vertebrates. Beneficially, hand mutants are viable and exhibit affected tissues, which renders Drosophila an ideal model to investigate up- or downregulated target genes by a comparative microarray approach focusing on the respective tissues from mutant specimens. Our present work reveals for the first time that Drosophila Hand regulates the expression of numerous genes of diverse physiological relevancy, including distinct factors required for proper muscle development and function such as Zasp52 or Msp-300. These results relate Hand activity to muscle integrity and functionality and may thus be highly beneficial to the evaluation of corresponding hand phenotypes.
authors.affiliation: Department of Zoology/Developmental Biology, University of Osnabrück, 49069 Osnabrück, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hallier
authors.affiliation: Department of Animal Physiology, University of Kiel, 24098 Kiel, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoffmann
authors.affiliation: Department of Animal Physiology, University of Kiel, 24098 Kiel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Roeder
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom.
authors.forename: Markus
authors.initials: M
authors.lastname: Tögel
authors.affiliation: Department of Zoology/Developmental Biology, University of Osnabrück, 49069 Osnabrück, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Meyer
authors.affiliation: Department of Zoology/Developmental Biology, University of Osnabrück, 49069 Osnabrück, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Paululat
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development / Q000502:physiology*; D024510:Muscle Development / Q000235:genetics; D009132:Muscles / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; C475488:Hand protein, Drosophila