title: The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts.
abstract: The body wall muscle of a Drosophila larva is generated by fusion between founder cells and fusion-competent myoblasts (FCMs). Initially, a founder cell recognizes and fuses with one or two FCMs to form a muscle precursor, then the developing syncitia fuses with additional FCMs to form a muscle fiber. These interactions require members of the immunoglobulin superfamily (IgSF), with Kin-of-IrreC (Kirre) and Roughest (Rst) functioning redundantly in the founder cell and Sticks-and-stones (Sns) serving as their ligand in the FCMs. Previous studies have not resolved the role of Hibris (Hbs), a paralog of Sns, suggesting that it functions as a positive regulator of myoblast fusion and as a negative regulator that antagonizes the activity of Sns. The results herein resolve this issue, demonstrating that sns and hbs function redundantly in the formation of several muscle precursors, and that loss of one copy of sns enhances the myoblast fusion phenotype of hbs mutants. We further show that excess Hbs rescues some fusion in sns mutant embryos beyond precursor formation, consistent with its ability to drive myoblast fusion, but show using chimeric molecules that Hbs functions less efficiently than Sns. In conjunction with a physical association between Hbs and SNS in cis, these data account for the previously observed UAS-hbs overexpression phenotypes. Lastly, we demonstrate that either an Hbs or Sns cytodomain is essential for muscle precursor formation, and signaling from IgSF members found exclusively in the founder cells is not sufficient to direct precursor formation.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Claude
authors.initials: C
authors.lastname: Shelton
authors.forename: Kiranmai S
authors.initials: KS
authors.lastname: Kocherlakota
authors.forename: Shufei
authors.initials: S
authors.lastname: Zhuang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Abmayr
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002448:Cell Adhesion; D002459:Cell Fusion; D017931:DNA Primers / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017344:Genes, Insect; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D009154:Mutation; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D007136:Immunoglobulins; D008565:Membrane Proteins; C410904:SNS protein, Drosophila; C442230:hbs protein, Drosophila