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Myoblast fusion is critical for the formation, growth and maintenance of skeletal muscle throughout life. Myoblasts must undergo a complex series of molecular and morphological changes prior to fusing with one another. A number of extracellular, cell surface and intracellular molecules have been discovered that act to finely coordinate the cellular and molecular events that are intimately associated with, and influence the ability of muscle cells to fuse. This review discusses the molecules that regulate myoblast elongation, migration, adhesion and cytoskeletal alterations. Understanding the molecular mechanisms by which myoblast fusion is regulated is both of general biologic interest and may also lead to new strategies for manipulating myoblasts in disease, repair and aging and enhancing muscle growth. In addition, promotion of cell fusion may aid in cell therapy approaches involving transplantation of muscle stem cells. [ABSTRACT FROM AUTHOR]

The larval musculature of Drosophila arises by fusion of two types of myoblasts: the founder cells (FCs), which determine the identity of every individual muscle, and fusion competent myoblasts (FCMs). Cell–cell recognition and adhesion is mediated by the Ig class of transmembrane proteins. They form an adhesion ring/belt at the contact sites of FCMs and FCs/growing myotubes to establish a Fusion Restricted Myogenic Adhesive Structure (FuRMAS). FuRMAS are postulated to trigger myoblast fusion, with the formation, and dissolution of F-actin foci/plugs at the sites of cell–cell contact. Electron-dense vesicles accumulate at opposing membranes of FCMs and FCs/growing muscles, and form a pre-fusion complex (1 μm²). This is hypothesised to take place in the centre of the FuRMAS. The vesicles are thought to be exocytosed, followed by membrane vesiculation and removal of membrane remnants to achieve cytoplasmic continuity over an area of 12 μm². The FCM can then be integrated into the growing myotube. This last step depends on Arp2/3 mediated F-actin reorganisation. The data on cell adhesion, signalling and actin regulation in zebrafish, C2C12 cells and mice strongly indicate conserved factors and principles between Drosophila and vertebrate myoblast fusion. [ABSTRACT FROM AUTHOR]