title: Glycolysis supports embryonic muscle growth by promoting myoblast fusion.
abstract: Muscles ensure locomotion behavior of invertebrate and vertebrate organisms. They are highly specialized and form using conserved developmental programs. To identify new players in muscle development we screened Drosophila and zebrafish gene expression databases for orthologous genes expressed in embryonic muscles. We selected more than 100 candidates. Among them is the glycolysis gene Pglym78/pgam2, the attenuated expression of which results in the formation of thinner muscles in Drosophila embryos. This phenotype is also observed in fast muscle fibers of pgam2 zebrafish morphants, suggesting affected myoblast fusion. Indeed, a detailed analysis of developing muscles in Pglym78 RNAi embryos reveals loss of fusion-associated actin foci and an inefficient Notch decay in fusion competent myoblasts, both known to be required for fusion. In addition to Pglym78, our screen identifies six other genes involved in glycolysis or in pyruvate metabolism (Pfk, Tpi, Gapdh, Pgk, Pyk, and Impl3). They are synchronously activated in embryonic muscles and attenuation of their expression leads to similar muscle phenotypes, which are characterized by fibers with reduced size and the presence of unfused myoblasts. Our data also show that the cell size triggering insulin pathway positively regulates glycolysis in developing muscles and that blocking the insulin or target of rapamycin pathways phenocopies the loss of function phenotypes of glycolytic genes, leading to myoblast fusion arrest and reduced muscle size. Collectively, these data suggest that setting metabolism to glycolysis-stimulated biomass production is part of a core myogenic program that operates in both invertebrate and vertebrate embryos and promotes formation of syncytial muscles.
authors.affiliation: Unité de Génétique, Reproduction et Développement, Institut National de la Santé et de la Recherche Médicale U1103, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6293, University of Clermont-Ferrand, 63001 Clermont-Ferrand, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tixier
authors.forename: Laetitia
authors.initials: L
authors.lastname: Bataillé
authors.forename: Christelle
authors.initials: C
authors.lastname: Etard
authors.forename: Teresa
authors.initials: T
authors.lastname: Jagla
authors.forename: Meltem
authors.initials: M
authors.lastname: Weger
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Daponte
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
authors.forename: Thomas
authors.initials: T
authors.lastname: Dickmeis
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jagla
mesh_terms: D000818:Animals; D002459:Cell Fusion; D004330:Drosophila / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D015726:Giant Cells / Q000502:physiology*; D006019:Glycolysis / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D007328:Insulin / Q000378:metabolism; D009132:Muscles / Q000196:embryology*; D032446:Myoblasts / Q000502:physiology*; D011770:Pyruvate Kinase / Q000378:metabolism; D034622:RNA Interference; D018709:Statistics, Nonparametric; D015027:Zebrafish
chemical_list: D007328:Insulin; D011770:Pyruvate Kinase
keywords: Danio rerio; morpholino