{"title":"Dynamic interactions between cartilaginous and tendinous/ligamentous primordia during musculoskeletal integration.","authors":"Xinyi Yu, Ryosuke Kawakami, Shinsei Yambe, Yuki Yoshimoto, Takako Sasaki, Shinnosuke Higuchi, Hitomi Watanabe, Haruhiko Akiyama, Shigenori Miura, Kadi Hu, Gen Kondoh, Ramu Sagasaki, Masafumi Inui, Taiji Adachi, Denitsa Docheva, Takeshi Imamura, Chisa Shukunami","doi":"10.1242/dev.204512","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11375,"journal":{"name":"Development","volume":"152 6","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Development","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1242/dev.204512","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/26 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Development’s scope covers all aspects of plant and animal development, including stem cell biology and regeneration. The single most important criterion for acceptance in Development is scientific excellence. Research papers (articles and reports) should therefore pose and test a significant hypothesis or address a significant question, and should provide novel perspectives that advance our understanding of development. We also encourage submission of papers that use computational methods or mathematical models to obtain significant new insights into developmental biology topics. Manuscripts that are descriptive in nature will be considered only when they lay important groundwork for a field and/or provide novel resources for understanding developmental processes of broad interest to the community.
Development includes a Techniques and Resources section for the publication of new methods, datasets, and other types of resources. Papers describing new techniques should include a proof-of-principle demonstration that the technique is valuable to the developmental biology community; they need not include in-depth follow-up analysis. The technique must be described in sufficient detail to be easily replicated by other investigators. Development will also consider protocol-type papers of exceptional interest to the community. We welcome submission of Resource papers, for example those reporting new databases, systems-level datasets, or genetic resources of major value to the developmental biology community. For all papers, the data or resource described must be made available to the community with minimal restrictions upon publication.
To aid navigability, Development has dedicated sections of the journal to stem cells & regeneration and to human development. The criteria for acceptance into these sections is identical to those outlined above. Authors and editors are encouraged to nominate appropriate manuscripts for inclusion in one of these sections.
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