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This study investigates how mechanical forces from muscle contractions regulate embryonic tendon development, using a mouse muscle paralysis model (muscular dysgenesis, mdg). The researchers found that paralyzed tendons exhibit structural and functional deficits due to reduced cell proliferation and disorganized collagen fibrils, alongside dysregulation of extracellular matrix components and cytoskeletal proteins. Notably, TGFΞ² signaling, which normally arrests during tendon growth, remains abnormally prolonged in paralyzed embryos, and muscle contraction is identified for the first time as necessary for the formation of the epitenon, the tendon's outer cellular sheath.
Why it matters
These findings provide new molecular and cellular insights into how physical loading shapes tendon tissue during development, which could inform strategies for tendon repair, regeneration, and the treatment of tendon disorders linked to immobility or developmental defects.
β οΈ Preprint β Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhΓ€ngigen Experten begutachtet. Die Ergebnisse sind vorlΓ€ufig und sollten mit Vorsicht interpretiert werden.
Muscle loading is required for embryonic tendon growth; however, the underlying mechanisms that regulate tendon development downstream of mechanical cues remain unidentified. Although tendons in muscle paralysis models are structurally and functionally inferior, whether these differences arise from cell or matrix deficits remains unclear. Analysis of muscular dysgenesis embryos by atomic force microscopy showed that structural and functional deficits in paralyzed tendon arise in part from reduced proliferation and collagen fibril disorganization. Bulk and single cell transcriptional analyses reveal that both collagenous and non-collagenous extracellular matrix components, as well as cytoskeletal and actomyosin-associated proteins, are dysregulated in mdg tendons, whereas tendon markers remain unchanged. Surprisingly, we find that an arrest of TGF{beta} signaling occurs during normal embryonic tendon growth and that TGF{beta} signaling is abnormally prolonged in paralyzed embryos. We also show for the first time, that specification of the epitenon depends on muscle contraction. Together, these findings establish cell and molecular requirements for muscle contraction in embryonic tendon development.