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Significance Myoblast fusion is essential for multinucleated muscle fiber formation. Regulators of fusion have been identified inDrosophila , but the molecular mechanisms controlling vertebrate myoblast fusion are poorly understood. We describe here previously unidentified in vivo functional evidence that the G-protein coupled receptor brain-specific angiogenesis inhibitor (BAI3) is a receptor controlling myoblast fusion in developing vertebrate muscles. We show that BAI3 binds the intracellular effector of myoblast fusion ELMO/DOCK1 and that this binding is obligatory for fusion. Using in vivo manipulations in the chicken embryo, we demonstrate that BAI3 binding to ELMO is essential for myoblast fusion. These experiments identify BAI3 as a long-sought-after receptor controlling vertebrate myoblast fusion.

G-protein coupled receptor BAI3 promotes myoblast fusion in vertebrates