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

2012; National Academy of Sciences; Volume: 109; Issue: 28 Linguagem: Inglês

10.1073/pnas.1116065109

1091-6490

Yael Gruenbaum‐Cohen, Itamar Harel, Kfir Baruch Umansky, Eldad Tzahor, Scott B. Snapper, Ben‐Zion Shilo, Eyal D. Schejter,

Genetics, Aging, and Longevity in Model Organisms

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.