Mechanism of muscle–tendon–bone complex development in the head

The musculoskeletal system comprises muscles, tendons, ligaments, and bones. The connection site between muscle and tendon is termed “myotendinous junction,” while the junction between tendon/ligament and bone is termed “enthesis.” These two regions are the center of physical function, but how this functional complex is formed during development is unclear. In this review, we discussed recent findings about the development of tissues constituting the musculoskeletal system and the interactions among these tissues during development. The musculoskeletal system of the head develops in the mid-embryonic stage. In addition, head mesoderm-derived cells (muscle anlagen) and cranial neural crest cells (tendon and bone anlagen) interact with each other. Myogenesis initiates in the head without difficulty, even in the absence of cranial neural crest cells; however, muscle tissue does not grow under these conditions and remains small. Tendons, which differentiate from cranial neural crest cells, form myotendinous junctions at the stage at which desmin accumulates in the tendon-side muscle stump, leading to morphological maturation. Therefore, individual tissues (i.e., muscles, tendons, ligaments, and bones) constituting the musculoskeletal system form a functionally important complex, while mutually influencing one another.