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 doubletransgenic 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. The musculoskeletal system comprises muscles, tendons, and bones. It is an efficient tissue complex that coordinates body movement and maintains structural stability 1. This requires effective linkage of muscles to bones. Many studies have reported the development of each component of the musculoskeletal system, but the process of its construction into a single functional and complex organization is unclear. Muscles, tendons, and bones differ in their developmental origins 2-8 , yet they interact during differentiation. Chen and Galloway 8 reported that artificial rupture of the myotome impedes syndetome formation. In contrast, cranial tendon progenitor cells emerge without dependence on muscles, yet muscle presence is essential for their normal differentiation 8. Huang et al 9. analyzed tendon development in forearms and fingers and found that tendons can be divided into a distal module showing cartilage-dependent development and a proximal module showing muscle-dependent development. In addition, the mechanical stress of muscle contraction affects the morphology of cartilage and bone during development 10. Previously, we found that mutual contact between muscles and the tendon-like structure immediately promotes the development of bones 11 and that there is a morphological association between muscles and bones 12. In summary, studies need to focus on the analysis of muscles, tendons, and bones as a single functional organ 13 rather than focusing on each as an independent tissue component. SRY-box containing gene 9 (Sox9) is a transcription factor essential for musculoskeletal system development. Sox9 is expressed in all cartilage progenitor cells and cartilage cells except hypertrophic chondrocytes 14,15 , and it plays a key role in a series of processes involved in endochondral...

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In an attempt to clarify the function of the suboccipital muscles, we performed morphological observation of the suboccipital muscles for variations in the muscle belly and compared the morphology of their muscle fibers in terms of cross-sectional area by immunostaining with anti-myosin heavy chain antibodies. The cadavers of 25 Japanese individuals were used: 22 for morphological examinations and three for histological examinations. Among samples of the rectus capitis posterior major muscle (RCPma) and rectus capitis posterior minor muscle (RCPmi), 86.4% had a typical muscle appearance with a single belly, and 13.6% had an anomalous morphology. None of the samples of the obliquus capitis superior (OCS) or obliquus capitis inferior (OCI) muscles had an anomalous appearance. Measurement of cross-sectional area revealed that fast-twitch muscle fibers in the RCPma and OCI had a significantly greater cross-sectional area than those of the RCPmi and OCS. The cross-sectional area of intermediate muscle fibers was also significantly greater in the OCS than in the RCPma, RCPmi, and OCI. The cross-sectional area of slow-twitch muscle fibers was significantly greater in the OCS than in the RCPma, RCPmi, and OCI, and the RCPmi showed a significantly greater cross-sectional area for slow-twitch muscle fibers than did the RCPma, and OCI. Our findings indicate that the RCPmi and OCS exert a greater force than the RCPma and OCI, and act as anti-gravity agonist muscles of the head. Prolonged head extension in individuals with anomalous suboccipital muscle groups could result in dysfunction due to undue stress.