Abstract
Author SummaryThe fusion of precursor cells is a crucial step in many biological processes, one of which is the development of skeletal muscle. The molecular and cell biology of fusion of muscle precursors has been well described in Drosophila melanogaster larvae, leading to insights into the process in vertebrates. However, the identity and mechanism of action of essential cell surface proteins for fusion between vertebrate muscle precursors has previously been lacking. Here, we describe a vertebrate-specific cell surface receptor pair that is essential for fusion in zebrafish: Jamb and Jamc. Loss of function of either receptor causes a near-complete block in fusion, resulting in an overabundance of mononucleate muscle fibres that are otherwise overtly normal. We demonstrate that Jamb and Jamc physically interact and are co-expressed by muscle precursors. Moreover, we show that the interaction between them is essential for fusion between neighbouring precursors in an embryo. We hypothesise that binding of Jamb to Jamc is a necessary recognition and adhesion step permissive for, but not sufficient to cause, myocyte fusion. Knowledge of these molecular components in vertebrates will lead to better understanding of how fusion is controlled to pattern skeletal muscle tissue.
Highlights
Cell–cell fusion is crucial for several biological processes, including placental development [1], bone remodelling [2], fertilisation [3], and formation of skeletal muscle fibres [4], but surprisingly remains poorly understood
We identify two vertebrate cell surface receptors that are crucial for myocyte fusion: Jamb and Jamc
We have shown here that jamb and jamc are co-expressed in developing myoblasts and, by using mutant zebrafish, demonstrate that the physical interaction between them is essential for myocyte fusion in vivo
Summary
Cell–cell fusion is crucial for several biological processes, including placental development [1], bone remodelling [2], fertilisation [3], and formation of skeletal muscle fibres [4], but surprisingly remains poorly understood. Skeletal muscle forms the bulk of tissue in vertebrates and is composed of bundles of long syncytial fibres formed by the fusion of post-mitotic muscle precursor cells (myocytes). A critical step in fusion is the initial recognition and adhesion between the two cell types This is regulated by the mutually exclusive expression of the cell surface receptor proteins Kirre and Sns, which form a heterophilic receptor pair between neighbouring cells [12,13,14,15,16,17]. Loss-offunction studies of these candidates resulted in mild disruption of myocyte fusion in vivo, leading to the view that this process involves several partially redundant proteins in vertebrates [18].
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