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Publication : Dynamic interactions between cartilaginous and tendinous/ligamentous primordia during musculoskeletal integration.

First Author  Yu X Year  2025
Journal  Development Volume  152
Issue  6 PubMed ID  40135875
Mgi Jnum  J:364145 Mgi Id  MGI:8166877
Doi  10.1242/dev.204512 Citation  Yu X, et al. (2025) Dynamic interactions between cartilaginous and tendinous/ligamentous primordia during musculoskeletal integration. Development 152(6):dev204512
abstractText  Proper connections between cartilaginous and muscular primordia through tendinous/ligamentous primordia are essential for musculoskeletal integration. Herein, we report a novel double-reporter mouse model for investigating this process via fluorescently visualising scleraxis (Scx) and SRY-box containing gene 9 (Sox9) expression. We generated ScxTomato transgenic mice and crossed them with Sox9EGFP knock-in mice to obtain ScxTomato;Sox9EGFP mice. Deep imaging of optically cleared double-reporter embryos at E13.5 and E16.5 revealed previously unknown differences in the dynamic interactions between cartilaginous and tendinous/ligamentous primordia in control and Scx-deficient mice. Tendon/ligament maturation was evaluated through simultaneous detection of fluorescence and visualisation of collagen fibre formation using second harmonic generation imaging. Lack of deltoid tuberosity in Scx-deficient mice caused misdirected muscle attachment with morphological changes. Loss of Scx also dysregulated progenitor cell fate determination in the chondrotendinous junction, resulting in the formation of a rounded enthesis rather than the protruding enthesis observed in the control. Hence, our double-reporter mouse system, in combination with loss- or gain-of-function approaches, is a unique and powerful tool that could be used to gain a comprehensive understanding of musculoskeletal integration.
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