Visualizing new dimensions in <i>Drosophila</i> myoblast fusion

Richardson, Brian E.; Beckett, Karen; Baylies, Mary K.

doi:10.1002/bies.20756

Cited by 19 publications

(21 citation statements)

References 58 publications

(124 reference statements)

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“…However, the ability of Hbs to drive fusion beyond precursor formation when in excess, and the observation that removal of one copy of sns enhances fusion defects in hbs mutants, suggests that Hbs can assist in later rounds of myoblast fusion. These data are consistent with models in which molecular interactions in precursor formation and subsequent fusion differ kinetically but not genetically Richardson et al, 2008). One possibility, independent of the process of fusion itself, is that Sns and Hbs differ in their ability to drive FCM cell migration.…”

Section: Hbs Does Not Replace Sns: Implications For Signal Transductisupporting

confidence: 87%

“…An alternative model, using three dimensional analyses and quantitating fusing myoblasts over time, revealed that fusion occurs in two temporal phases, comprising an initial phase of limited fusion between cells that are in close proximity and a second phase when most myoblast fusion occurs . Moreover, precursor formation is temporally delayed in embryos lacking molecules such as Rols and Kette, suggesting that these molecules do influence the first step in fusion Richardson et al, 2008). The present study does not address whether the genetic requirements for precursor formation differ from those for subsequent rounds of fusion, or whether these steps utilize the same set of proteins.…”

Section: Hbs Does Not Replace Sns: Implications For Signal Transductimentioning

confidence: 79%

“…One possibility, independent of the process of fusion itself, is that Sns and Hbs differ in their ability to drive FCM cell migration. Although the role of cell migratory behavior in myoblast fusion is unclear, the ability to migrate may contribute to the rate of fusion Richardson et al, 2008). While these questions remain to be addressed, the present study advances our understanding of fusion by resolving the interaction of two proteins that function early in the process, thereby providing additional perspectives for sorting out the different mechanisms of myoblast fusion.…”

Section: Hbs Does Not Replace Sns: Implications For Signal Transductimentioning

confidence: 86%

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The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts

et al. 2009

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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.

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Section: Hbs Does Not Replace Sns: Implications For Signal Transductisupporting

confidence: 87%

Section: Hbs Does Not Replace Sns: Implications For Signal Transductimentioning

confidence: 79%

Section: Hbs Does Not Replace Sns: Implications For Signal Transductimentioning

confidence: 86%

See 1 more Smart Citation

The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts

et al. 2009

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“…Furthermore, we describe transient F-actin structures that form in myoblasts near the onset of fusion, under the influence of the Arp2/3 actin polymerization machinery, but independently of the Wsp and SCAR nucleating systems. These findings underscore the significant roles played by the actin-based cytoskeleton in the myoblast fusion process (Onel and Renkawitz-Pohl, 2009;Richardson et al, 2008), and, in particular, generalize and accentuate the myogenic role of the WASp pathway.…”

Section: Introductionmentioning

confidence: 54%

The actin nucleator WASp is required for myoblast fusion during adultDrosophilamyogenesis

et al. 2011

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SUMMARYMyoblast fusion provides a fundamental, conserved mechanism for muscle fiber growth. We demonstrate here that the functional contribution of Wsp, the Drosophila homolog of the conserved actin nucleation-promoting factor (NPF) WASp, is essential for myoblast fusion during the formation of muscles of the adult fly. Disruption of Wsp function results in complete arrest of myoblast fusion in all muscles examined. Wsp activity during adult Drosophila myogenesis is specifically required for muscle cell fusion and is crucial both for the formation of new muscle fibers and for the growth of muscles derived from persistent larval templates. Although Wsp is expressed both in fibers and individual myoblasts, its activity in either one of these cell types is sufficient. SCAR, a second major Arp2/3 NPF, is also required during adult myoblast fusion. Formation of fusionassociated actin 'foci' is dependent on Arp2/3 complex function, but appears to rely on a distinct, unknown nucleator. The comprehensive nature of these requirements identifies Arp2/3-based branched actin polymerization as a universal mechanism underlying myoblast fusion.

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“…These studies indicate that these fusion genes are required for the dissolution of this structure during the fusion process and suggest that removal of this actin structure is crucial for fusion to proceed (Richardson et al, 2008a;Richardson et al, 2007). In addition, several studies proposed that this actin structure at the fusion site is required for vesicle trafficking (Kim et al, 2007) and/or enlarging fusion pores (Berger et al, 2008;Massarwa et al, 2007).…”

Section: Introductionmentioning

confidence: 95%

Nap1-mediated actin remodeling is essential for mammalian myoblast fusion

Nowak

Nahirney

Hadjantonakis

et al. 2009

Journal of Cell Science

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Myoblast fusion is crucial for the formation, growth, maintenance and regeneration of healthy skeletal muscle. Unfortunately, the molecular machinery, cell behaviors, and membrane and cytoskeletal remodeling events that govern fusion and myofiber formation remain poorly understood. Using time-lapse imaging approaches on mouse C2C12 myoblasts, we identify discrete and specific molecular events at myoblast membranes during fusion and myotube formation. These events include rearrangement of cell shape from fibroblast to spindle-like morphologies, changes in lamellipodial and filopodial extensions during different periods of differentiation, and changes in membrane alignment and organization during fusion. We find that actin-cytoskeleton remodeling is crucial for these events: pharmacological inhibition of F-actin polymerization leads to decreased lamellipodial and filopodial extensions and to reduced myoblast fusion. Additionally, shRNA-mediated inhibition of Nap1, a member of the WAVE actin-remodeling complex, results in accumulations of F-actin structures at the plasma membrane that are concomitant with a decrease in myoblast fusion. Our data highlight distinct and essential roles for actin cytoskeleton remodeling during mammalian myoblast fusion, provide a platform for cellular and molecular dissection of the fusion process, and suggest a functional conservation of Nap1-regulated actin-cytoskeleton remodeling during myoblast fusion between mammals and Drosophila.Supplementary material available online at

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Visualizing new dimensions in Drosophila myoblast fusion

Cited by 19 publications

References 58 publications

The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts

The immunoglobulin superfamily member Hbs functions redundantly with Sns in interactions between founder and fusion-competent myoblasts

The actin nucleator WASp is required for myoblast fusion during adultDrosophilamyogenesis

Nap1-mediated actin remodeling is essential for mammalian myoblast fusion

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