Surface apposition and multiple cell contacts promote myoblast fusion in <i>Drosophila</i> flight muscles

Dhanyasi, Nagaraju; Segal, Dagan; Shimoni, Eyal; Shinder, Vera; Shilo, Ben‐Zion; VijayRaghavan, K.; Schejter, Eyal D.

doi:10.1083/jcb.201503005

Cited by 40 publications

(46 citation statements)

References 79 publications

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“…The ultrastructural features of this heterocellular interaction were exceedingly similar to the apposition and flattening observed between myoblasts and myotubes before cell fusion 17 (Supplemental Fig. 1).…”

Section: Resultssupporting

confidence: 54%

Skeletal muscle regeneration involves macrophage-myoblast bonding

Ceafalan

Fertig

Popescu

et al. 2017

Cell Adhesion & Migration

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Regeneration in adult skeletal muscle relies on the activation, proliferation, and fusion of myogenic precursor cells (MPC), mostly resident satellite cells (SC). However, the regulatory mechanism during this process is still under evaluation, with the final aim to manipulate regeneration when the intrinsic mechanism is corrupted. Furthermore, intercellular connections during skeletal muscle regeneration have not been previously thoroughly documented. Our hypothesis was that a direct and close cellular interaction between SC/MPC and invading myeloid cells is a key step to control regeneration. We tested this hypothesis during different steps of skeletal muscle regeneration: (a) the recruitment of activated SC; (b) the differentiation of MPC; (c) myotubes growth, in a mouse model of crush injury. Samples harvested (3 and 5 days) post-injury were screened by light and confocal microscopy. Ultrastructural analysis was performed by conventional transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) followed by 3D modeling of electron tomography (ET) data. This revealed a new type of interaction between macrophages and myogenic cells by direct heterocellular surface apposition over large areas and long linear distances. In the analyzed volume, regions spaced below 20 nm, within molecular range, represented 31% of the macrophage membrane surface and more than 27% of the myotube membrane. The constant interaction throughout all stages of myogenesis suggests a potential new type of regulatory mechanism for the myogenic process. Thus, deciphering structural and molecular mechanisms of SC-macrophage interaction following injury might open promising perspectives for improving muscle healing.

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Section: Resultssupporting

confidence: 54%

Skeletal muscle regeneration involves macrophage-myoblast bonding

Ceafalan

Fertig

Popescu

et al. 2017

Cell Adhesion & Migration

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“…http://dx.doi.org/10.1101/037838 doi: bioRxiv preprint first posted online Jan. 25, 2016; have been important for the analysis of corresponding mechanisms in vertebrates (1, 6, 23-25) With the identification of satellite cells in Drosophila the wealth of classical and molecular genetic tools available in this model system can now be applied to the mechanistic analysis adult-specific stem cell action in myogenic homeostasis and repair. Given the understanding of various fusion molecules involved in early stages of myogenesis, it will also be interesting to investigate a possible conservation of the fusion molecular machinery for regeneration and repair in the adult (12,26). Finally, in view of the evidence for age and disease-related decline in satellite cell number and function in humans (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…The IFMs are composed of the dorsoventral muscles (DVMs) formed by the de novo fusion of myoblast and the dorsal longitudinal muscles (DLMs) which are formed using remnant larval muscles as templates. (10)(11)(12).…”

Section: Two Different Types Of Cells Are Present In Adult Flight Musclementioning

confidence: 99%

Identification and Functional Characterization of Muscle Satellite Cells in Drosophila

Gunage¹,

Reichert²,

VijayRaghavan³

2016

Preprint

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Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates.In this study we show that lineal descendants of muscle stem cells are present in adult muscle of Drosophila as small, unfused cells located superficially and in close proximity to the mature muscle fibers.Normally quiescent, following muscle fiber injury, we show that these cells express Zfh1-cells and engage in Notch-Delta dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of strikingly similar morphological and functional features, we consider these novel cells to be the Drosophila equivalent of vertebrate muscle satellite cells.

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“…In this system, intracellular signaling results in cytoskeletal alterations and actin polymerization, which drive the formation of cellular projections that invade neighboring cells to cause fusion (3). Recent evidence also indicates a critical function for branched actin polymerization during Drosophila indirect flight muscle fusion (4). The essential role of the cytoskeleton in fusion is conserved in mammals, in which the actin regulators Rac1, cdc42, and N-WASp are required for muscle development (5)(6)(7)(8).…”

mentioning

confidence: 99%

Structure–function analysis of myomaker domains required for myoblast fusion

Millay

Gamage

Quinn

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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During skeletal muscle development, myoblasts fuse to form multinucleated myofibers. Myomaker [Transmembrane protein 8c (TMEM8c)] is a muscle-specific protein that is essential for myoblast fusion and sufficient to promote fusion of fibroblasts with muscle cells; however, the structure and biochemical properties of this membrane protein have not been explored. Here, we used CRISPR/Cas9 mutagenesis to disrupt myomaker expression in the C2C12 muscle cell line, which resulted in complete blockade to fusion. To define the functional domains of myomaker required to direct fusion, we established a heterologous cell-cell fusion system, in which fibroblasts expressing mutant versions of myomaker were mixed with WT myoblasts. Our data indicate that the majority of myomaker is embedded in the plasma membrane with seven membrane-spanning regions and a required intracellular C-terminal tail. We show that myomaker function is conserved in other mammalian orthologs; however, related family members (TMEM8a and TMEM8b) do not exhibit fusogenic activity. These findings represent an important step toward deciphering the cellular components and mechanisms that control myoblast fusion and muscle formation.P lasma membrane fusion is a fundamental cellular process required for the conception, development, and physiology of multicellular organisms. Membrane fusion occurs during viral infection of a host cell, between intracellular membranes, and between two plasma membranes to form syncytial tissues (1). Cell-cell fusion is critical for a wide array of cellular processes, including sperm-egg fertilization, macrophage function, bone and placental development, and skeletal muscle formation. This form of fusion must be precisely controlled to prevent inappropriate cellular mixing.The fusion of myoblasts requires cell recognition, migration, adhesion, signaling, and finally, membrane coalescence (2). Much of our knowledge about myoblast fusion has originated from studies performed in Drosophila. In this system, intracellular signaling results in cytoskeletal alterations and actin polymerization, which drive the formation of cellular projections that invade neighboring cells to cause fusion (3). Recent evidence also indicates a critical function for branched actin polymerization during Drosophila indirect flight muscle fusion (4). The essential role of the cytoskeleton in fusion is conserved in mammals, in which the actin regulators Rac1, cdc42, and N-WASp are required for muscle development (5-8). In addition to actin dynamics, numerous proteins that regulate diverse cellular processes have been associated with myoblast fusion (9-13).We recently discovered a muscle-specific membrane protein named myomaker [annotated as Transmembrane protein 8c (TMEM8c)] that is absolutely required for skeletal myocyte fusion in the mouse (14,15). To begin to decipher the mechanisms whereby myomaker controls cell-cell fusion, we designed a heterologous cell-cell fusion assay to monitor the ability of a series of myomaker mutants to direct the fusion of lab...

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Surface apposition and multiple cell contacts promote myoblast fusion in Drosophila flight muscles

Cited by 40 publications

References 79 publications

Skeletal muscle regeneration involves macrophage-myoblast bonding

Skeletal muscle regeneration involves macrophage-myoblast bonding

Identification and Functional Characterization of Muscle Satellite Cells in Drosophila

Structure–function analysis of myomaker domains required for myoblast fusion

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