Stereotypic generation of axial tenocytes from bipartite sclerotome domains in zebrafish

Development of a functional musculoskeletal system requires coordinated generation of muscles, bones, and tendons. However, how axial tendon cells (tenocytes) are generated during embryo development is still poorly understood. Here, we show that axial tenocytes arise from the sclerotome in zebrafish. In contrast to mouse and chick, the zebrafish sclerotome consists of two separate domains: a ventral domain and a previously undescribed dorsal domain. While dispensable for sclerotome induction, Hedgehog (Hh) signaling is required for the migration and maintenance of sclerotome derived cells. Axial tenocytes are located along the myotendinous junction (MTJ), extending long cellular processes into the intersomitic space. Using time-lapse imaging, we show that both sclerotome domains contribute to tenocytes in a dynamic and stereotypic manner. Tenocytes along a given MTJ always arise from the sclerotome of the adjacent anterior somite. Inhibition of Hh signaling results in loss of tenocytes and enhanced sensitivity to muscle detachment. Together, our work shows that axial tenocytes in zebrafish originate from the sclerotome and are essential for maintaining muscle integrity.

功能性肌肉骨骼系统的发育需要肌肉、骨骼与肌腱的协同生成。然而，胚胎发育过程中轴位腱细胞（tenocytes）的生成机制仍不甚明晰。本研究证实，斑马鱼的轴位腱细胞起源于生骨节（sclerotome）。与小鼠和鸡胚不同，斑马鱼的生骨节包含两个独立区域：腹侧区域以及此前未被报道的背侧区域。尽管Hedgehog（Hh）信号通路对生骨节诱导并非必需，但却是生骨节来源细胞的迁移与维持所不可或缺的。轴位腱细胞沿肌肌腱连接（myotendinous junction, MTJ）分布，并向体节间隙伸出细长的细胞突起。通过延时成像（time-lapse imaging）分析，我们发现两个生骨节区域均以动态且刻板的方式参与腱细胞的生成。特定肌肌腱连接处的腱细胞始终起源于相邻前体节的生骨节。抑制Hh信号通路会导致腱细胞缺失，并加剧肌肉脱离的易感性。综上，本研究表明斑马鱼的轴位腱细胞起源于生骨节，且对维持肌肉完整性至关重要。