How does membrane ultrastructure change to support skeletal muscle myogenesis and regeneration?
Skeletal muscle myogenesis necessitates extensive membrane remodeling for the cells to fuse and subsequently establish the unique membrane ultrastructure of the multinucleated contractile muscle fiber. Cell fusion is also essential for muscle regeneration throughout life, raising important questions about the mechanisms of fusion and the maintenance of the mature muscle fiber ultrastructure in the face of the continuous addition of cells. A lack of methods to capture myoblasts at specific stages of differentiation and fusion has been a major obstacle to research in this area. We recently overcame this barrier by discovering that ERK1/2 inhibition in primary vertebrate myoblasts leads to synchronous and robust initiation of the differentiation program1,2. This breakthrough enables us to identify new putative players in the fusion process and visualize the dynamic fusogenic synapse that forms between myoblast and myotube, with high spatial and temporal resolution1,2. These findings are a significant advance toward elucidating the molecular mechanisms controlling myoblast fusion and integration.
Fusion between myoblasts. Video by Giulia Zarfati.