An efficient musculoskeletal system depends on the precise assembly and coordinated growth and function of muscles, skeleton, and tendons. However, the mechanisms that drive integrated musculoskeletal development and coordinated growth and differentiation of each of these tissues are still being uncovered. Epigenetic modifiers have emerged as critical regulators of cell fate differentiation, but so far almost nothing is known about their roles in tendon biology. Previous studies have shown that epigenetic modifications driven by Enhancer of zeste homolog 2 (EZH2), a major histone methyltransferase, have significant roles in vertebrate development including skeletal patterning and bone formation. We now find that targeting Ezh2 through the limb mesenchyme also has significant effects on tendon and muscle patterning, likely reflecting the essential roles of early mesenchymal cues mediated by Ezh2 for coordinated patterning and development of all tissues of the musculoskeletal system. Conversely, loss of Ezh2 in the tendon cells did not disrupt overall tendon structure or collagen organization suggesting that tendon differentiation and maturation are independent of Ezh2 signaling.

中文翻译：

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Ezh2 对于多个肌肉骨骼组织的图案化至关重要，但对于肌腱分化是可有可无的

一个有效的肌肉骨骼系统依赖于肌肉、骨骼和肌腱的精确组装和协调的生长和功能。然而，驱动这些组织的综合肌肉骨骼发育以及协调生长和分化的机制仍未被发现。表观遗传修饰剂已成为细胞命运分化的关键调节剂，但到目前为止，它们在肌腱生物学中的作用几乎一无所知。先前的研究表明，由主要组蛋白甲基转移酶 zeste 同源物 2 (EZH2) 增强子驱动的表观遗传修饰在脊椎动物发育中具有重要作用，包括骨骼模式和骨形成。我们现在发现针对Ezh2通过肢体间充质对肌腱和肌肉模式也有显着影响，可能反映了由Ezh2介导的早期间充质信号在协调肌肉骨骼系统所有组织的模式和发育中的重要作用。相反，肌腱细胞中Ezh2的缺失并未破坏整体肌腱结构或胶原组织，这表明肌腱分化和成熟与Ezh2信号传导无关。