Scleraxis-lineage cells are required for correct muscle patterning

Movement of the vertebrate body is supported by the connection of muscle, tendon and bone. Each skeletal muscle in the vertebrate body has a unique shape and attachment site; however, the mechanism that ensures reproducible muscle patterning is incompletely understood. In this study, we conducted targeted cell ablation using scleraxis (Scx)-Cre to examine the role of Scx-lineage cells in muscle morphogenesis and attachment in mouse embryos. We found that muscle bundle shapes and attachment sites were significantly altered in embryos with Scx-lineage cell ablation. Muscles in the forelimb showed impaired bundle separation and limb girdle muscles distally dislocated from their insertion sites. Scx-lineage cells were required for post-fusion myofiber morphology, but not for the initial segregation of myoblasts in the limb bud. Furthermore, muscles could change their attachment site, even after formation of the insertion. Lineage tracing suggested that the muscle patterning defect was primarily attributed to the reduction of tendon/ligament cells. Our study demonstrates an essential role of Scx-lineage cells in the reproducibility of skeletal muscle attachment, in turn revealing a previously unappreciated tissue-tissue interaction in musculoskeletal morphogenesis.

Automated summary

Movement of the vertebrate body is supported by the connection of muscle, tendon, and bone. A study using targeted cell ablation in mouse embryos reveals the essential role of Scx-lineage cells in muscle morphogenesis and attachment. The absence of these cells leads to altered muscle bundle shapes and attachment sites, impairments in muscle separation and dislocation of limb girdle muscles. Furthermore, lineage tracing suggests that the muscle patterning defect is primarily due to a reduction in tendon/ligament cells.