The musculoskeletal system is a striking example of how cell identity and position is coordinated across multiple tissues to ensure function. However, it is unclear upon tissue loss, such as complete loss of cells of a central musculoskeletal connecting tendon, whether neighboring tissues harbor progenitors capable of mediating regeneration. Here, using a zebrafish model, we genetically ablate all embryonic tendon cells and find complete regeneration of tendon structure and pattern. We identify two regenerative progenitor populations, sox10⁺ perichondrial cells surrounding cartilage and nkx2.5⁺ cells surrounding muscle. Surprisingly, laser ablation of sox10⁺ cells, but not nkx2.5⁺ cells, increases tendon progenitor number in the perichondrium, suggesting a mechanism to regulate attachment location. We find BMP signaling is active in regenerating progenitor cells and is necessary and sufficient for generating new scxa⁺ cells. Our work shows that muscle and cartilage connective tissues harbor progenitor cells capable of fully regenerating tendons, and this process is regulated by BMP signaling.

肌肉骨骼系统是如何在多个组织中协调细胞身份和位置以确保功能的一个突出例子。然而，尚不清楚在组织丢失时，例如中央肌肉骨骼连接肌腱的细胞完全丢失，相邻组织是否具有能够介导再生的祖细胞。在这里，我们使用斑马鱼模型对所有胚胎肌腱细胞进行基因消融，并找到肌腱结构和模式的完全再生。我们确定了两个再生祖细胞群，软骨周围的sox10 ⁺软骨膜细胞和肌肉周围的nkx2.5 ⁺细胞。令人惊讶的是，sox10 ⁺细胞的激光消融，而不是nkx2.5 ⁺细胞，增加了软骨膜中的肌腱祖细胞数量，表明存在调节附着位置的机制。我们发现 BMP 信号传导在再生祖细胞中是活跃的，并且对于生成新的scxa ⁺细胞是必要和充分的。我们的工作表明，肌肉和软骨结缔组织具有能够完全再生肌腱的祖细胞，并且该过程受 BMP 信号的调节。