The musculoskeletal system, which comprises muscles, tendons, and bones, is an efficient tissue complex that coordinates body movement and maintains structural stability. The process of its construction into a single functional and complex organization is unclear. SRY-box containing gene 9 (Sox9) is expressed initially in pluripotent cells and subsequently in ectodermal, endodermal, and mesodermal derivatives. This study investigated how Sox9 controls the development of each component of the musculoskeletal system. Sox9 was expressed in MTJ, tendon, and bone progenitor cells at E13 and in bone at E16. We detected Sox9 expression in muscle progenitor cells using double-transgenic mice and myoblastic cell lines. However, we found no Sox9 expression in developed muscle. A decrease in Sox9 expression in muscle-associated connective tissues, tendons, and bones led to hypoplasia of the cartilage and its attachment to tendons and muscle. These results showed that switching on Sox9 expression in each component (muscle, tendon, and bone) is essential for the development of the musculoskeletal system. Sox9 is expressed in not only tendon and bone progenitor cells but also muscle progenitor cells, and it controls musculoskeletal system development.
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