The actin regulator N-WASp is required for muscle-cell fusion in mice.
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.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Yael
Y
Gruenbaum-Cohen
Itamar
I
Harel
Kfir-Baruch
KB
Umansky
Eldad
E
Tzahor
Scott B
SB
Snapper
Ben-Zion
BZ
Shilo
Eyal D
ED
Schejter
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004330:Drosophila; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D024510:Muscle Development; D009132:Muscles / Q000166:cytology* / Q000196:embryology; D013997:Time Factors; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism*
D000199:Actins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal