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.

FuRMAS: triggering myoblast fusion in Drosophila

“…Whereas Artero et al (2001) suggested based on genetic interaction that SNS and Hbs function antagonistically, Dworak et al (2001) proposed that both genes act in functional redundancy. This finding was confirmed by double mutant experiments from Menon et al (2005) and Shelton et al (2009).…”

Sns and Kirre, theDrosophilaorthologs of Nephrin and Neph1,direct adhesion, fusion and formation of a slit diaphragm-like structure in insect nephrocytes

“…Previous studies have shown that Kirre and Rst serve redundant roles in the founder myoblasts (Strunkelnberg et al, 2001), and Sns and Hbs are both competent to direct the initial fusion event between fusion competent myoblasts and founder cells (Menon et al, 2005;Shelton et al, 2009). Whereas Rst expression has not been detected in the GCNs, we have observed significant expression of Hbs (data not shown).…”

“…In Drosophila, the Immunoglobulin superfamily (IgSF) proteins encoded by kin of irre [kirre; also known as dumbfounded (duf)], roughest (rst), sticks and stones (sns) and hibris (hbs) function as ligand-receptor pairs on the surface of founder cells and fusion competent myoblasts (Artero et al, 2001;Bour et al, 2000;Dworak et al, 2001;Ruiz-Gomez et al, 2000;Shelton et al, 2009;Strunkelnberg et al, 2001). These proteins mediate recognition, adhesion and fusion to form multinucleate syncitia through direct interaction at sites of myoblast contact.…”

Myoblast fusion: lessons from flies and mice

“…Hibris (Hbs), a paralog of Sns (Artero et al, 2001;Dworak et al, 2001) can direct a small amount of fusion in the absence of Sns, but is quite inefficient by comparison (Shelton et al, 2009). Whereas flies lacking Hbs are viable, muscle fibers are absent in sns mutant embryos and these embryos do not hatch as a result (Bour et al, 2000).…”