Nap1-mediated actin remodeling is essential for mammalian myoblast fusion

Nowak, Scott J.; Nahirney, Patrick C.; Hadjantonakis, Anna-Katerina; Baylies, Mary K.

doi:10.1242/jcs.047597

Cited by 96 publications

(107 citation statements)

References 69 publications

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“…The fusion between myotubes in vitro has previously been reported 31,32 , and it has also been suggested that some myofibres could fuse one to another in vivo during regeneration 33 . In our conditions, the fusion of two normal myotubes in vitro was a rare event as shown by videomicroscopy.…”

Section: Discussionmentioning

confidence: 85%

Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81

et al. 2013

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Skeletal muscle regeneration after injury follows a remarkable sequence of synchronized events. However, the mechanisms regulating the typical organization of the regenerating muscle at different stages remain largely unknown. Here we show that muscle regeneration in mice lacking either CD9 or CD81 is abnormal and characterized by the formation of discrete giant dystrophic myofibres, which form more quickly in the absence of both tetraspanins. We also show that, in myoblasts, these two tetraspanins associate with the immunoglobulin domain molecule CD9P-1 (EWI-F/FPRP), and that grafting of CD9P-1-depleted myoblasts in regenerating muscles also leads to abnormal regeneration. In vitro myotubes lacking CD9P-1 or both CD9 and CD81 fuse with a higher frequency than normal myotubes. Our study unveils a mechanism preventing inappropriate fusion of myotubes that has an important role in the restitution of normal muscle architecture during muscle regeneration.

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Section: Discussionmentioning

confidence: 85%

Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81

et al. 2013

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“…Importantly, a discrete actin-based structure associated with the fusion process in mammalian muscles is still missing. Indications that such structures may exist come from myogenic cell-culture studies (25,33), but have not been reported in vivo or in primary culture studies, and we were not able to identify them in the course of the current study.…”

Section: Discussionmentioning

confidence: 88%

“…Noteworthy in this context is the observed requirement for Nap1, a regulator of the WAVE NPF, during fusion of cultured murine myogenic cell lines (25). An essential involvement of WASp/WAVE-family elements in myoblast fusion has been previously established for the different phases of Drosophila myogenesis (21,(26)(27)(28)(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

The actin regulator N-WASp is required for muscle-cell fusion in mice

Gruenbaum-Cohen

Harel²,

Umansky³

et al. 2012

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

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A fundamental aspect of skeletal myogenesis involves extensive rounds of cell fusion, in which individual myoblasts are incorporated into growing muscle fibers. Here we demonstrate that N-WASp, a ubiquitous nucleation-promoting factor of branched microfilament arrays, is an essential contributor to skeletal muscle-cell fusion in developing mouse embryos. Analysis both in vivo and in primary satellite-cell cultures, shows that disruption of N-WASp function does not interfere with the program of skeletal myogenic differentiation, and does not affect myoblast motility, morphogenesis and attachment capacity. N-WASp-deficient myoblasts, however, fail to fuse. Furthermore, our analysis suggests that myoblast fusion requires N-WASp activity in both partners of a fusing myoblast pair. These findings reveal a specific role for N-WASp during mammalian myogenesis. WASp-family elements appear therefore to act as universal mediators of the myogenic cell-cell fusion mechanism underlying formation of functional muscle fibers, in both vertebrate and invertebrate species.actin nucleation | myotube formation

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“…This decrease in motility would increase the probability of cell-cell contact, thereby triggering differentiation (Krauss et al, 2005) and allowing myocytes to fuse with one another and with nascent myotubes (Nowak et al, 2009). As myotubes begin to form, muscle cells preferentially move into some fields and out of others (Chazaud et al, 1998), suggesting that migration is directed in response to chemotactic factors secreted by muscle cells (Bondesen et al, 2007;Griffin et al, 2010).…”

Section: Myoblast Migration Recognition and Adhesion In Micementioning

confidence: 99%

“…During differentiation in vitro, muscle cells extend lamellopodia and filopodia that contact neighboring muscle cells (Yoon et al, 2007;Mukai and Hashimoto, 2008;Mukai et al, 2009;Nowak et al, 2009;Stadler et al, 2010) and are sites for localized adhesion molecules (Abramovici and Gee, 2007;Mukai et al, 2009) and signaling molecules (Abramovici and Gee, 2007;Mukai and Hashimoto, 2008). These filopodia are reminiscent of axon growth cones and may be necessary for recognition of other muscle cells that are competent for fusion.…”

Section: Myoblast Migration Recognition and Adhesion In Micementioning

confidence: 99%

Myoblast fusion: lessons from flies and mice

2012

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The fusion of myoblasts into multinucleate syncytia plays a fundamental role in muscle function, as it supports the formation of extended sarcomeric arrays, or myofibrils, within a large volume of cytoplasm. Principles learned from the study of myoblast fusion not only enhance our understanding of myogenesis, but also contribute to our perspectives on membrane fusion and cell-cell fusion in a wide array of model organisms and experimental systems. Recent studies have advanced our views of the cell biological processes and crucial proteins that drive myoblast fusion. Here, we provide an overview of myoblast fusion in three model systems that have contributed much to our understanding of these events: the Drosophila embryo; developing and regenerating mouse muscle; and cultured rodent muscle cells. IntroductionThe process of fusing two adjacent membranes accomplishes many goals that are crucial to the development and maintenance of living organisms. Broadly, membrane fusion can occur intracellularly, as with synaptic vesicles, or between cells, as for sperm-egg fusion. Cell fusion occurs in a broad range of organisms, including Saccharomyces cerevisiae and Caenorhabditis elegans, and between several cell types, such as macrophages, placental trophoblasts and myoblasts. Experimental analysis of fusion in these systems has revealed the involvement of a diverse array of specialized molecules.Myoblast fusion, a fundamental step in the differentiation of muscle in most organisms, can involve tens of thousands of myoblasts, Given the complexity of the musculature, fusion must be a regulated process in which the appropriate number of cells fuse at the appropriate time and place. Often these cells migrate long distances prior to fusion, and fusion can involve multiple cell types, necessitating cell recognition and adhesion, which are crucial to accurate and efficient fusion. In addition to the early fusion events that occur during embryogenesis, vertebrate muscle tissue is able to regenerate in response to damage and disease. This regeneration involves proliferation of muscle satellite cells (see Glossary, Box 1) and their subsequent fusion to repair the damaged muscles. The focus of this review is the process of myoblast fusion, which involves cell migration, adhesion and signaling transduction pathways leading up to the actual fusion event. We review the crucial role of the actin cytoskeleton and actin polymerizing proteins, and recently revealed membrane protrusions that may drive fusion itself. We describe three powerful systems for this analysis: Drosophila embryogenesis; mouse embryogenesis and regeneration; and rodent tissue culture. We highlight the genes and morphological events involved in myoblast fusion, as revealed by each system. With the emergence of Danio rerio as another model for myoblast fusion, we also list relevant homologs in this system (Tables 1, 2). Experimental systems for the analysis of myoblast fusionThe ability to isolate and propagate mammalian myoblasts that could differentiate and fuse in...

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Nap1-mediated actin remodeling is essential for mammalian myoblast fusion

Cited by 96 publications

References 69 publications

Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81

Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81

The actin regulator N-WASp is required for muscle-cell fusion in mice

Myoblast fusion: lessons from flies and mice

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