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Skeletal muscle is formed by the iterative fusion of precursor cells (myocytes) into long multinuclear fibres. Extensive studies of fusion in Drosophila embryos have lead to a paradigm in which myoblasts are divided into two distinct subtypes - founder and fusion-competent myoblasts (FCMs) - that can fuse to each other, but not among themselves. Only founder cells can direct the formation of muscle fibres, while FCMs act as a cellular substrate. Recent studies in zebrafish and mice have demonstrated conservation of the molecules originally identified in Drosophila, but an important question remains: is vertebrate fusion regulated by specifying myocyte subtypes? Stated simply: do vertebrate founder cells exist? In light of recent findings, we argue that a different regulatory mechanism has evolved in vertebrates., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Cellular fusion is required in the development of several tissues, including skeletal muscle. In vertebrates, this process is poorly understood and lacks an in vivo-validated cell surface heterophilic receptor pair that is necessary for fusion. Identification of essential cell surface interactions between fusing cells is an important step in elucidating the molecular mechanism of cellular fusion. We show here that the zebrafish orthologues of JAM-B and JAM-C receptors are essential for fusion of myocyte precursors to form syncytial muscle fibres. Both jamb and jamc are dynamically co-expressed in developing muscles and encode receptors that physically interact. Heritable mutations in either gene prevent myocyte fusion in vivo, resulting in an overabundance of mononuclear, but otherwise overtly normal, functional fast-twitch muscle fibres. Transplantation experiments show that the Jamb and Jamc receptors must interact between neighbouring cells (in trans) for fusion to occur. We also show that jamc is ectopically expressed in prdm1a mutant slow muscle precursors, which inappropriately fuse with other myocytes, suggesting that control of myocyte fusion through regulation of jamc expression has important implications for the growth and patterning of muscles. Our discovery of a receptor-ligand pair critical for fusion in vivo has important implications for understanding the molecular mechanisms responsible for myocyte fusion and its regulation in vertebrate myogenesis. [ABSTRACT FROM AUTHOR]