Ligament injury in adult zebrafish triggers ECM remodeling and cell dedifferentiation for scar-free regeneration.

In mammals, when ligaments are injured, they often heal with the formation of scar tissue. However, a study in adult zebrafish has revealed a remarkable ability for scar-free healing in the jaw joint ligament. After surgically cutting this ligament, the researchers observed a breakdown of tissue near the injury, followed by the expansion of mesenchymal tissue in the wound site. This tissue then transformed into a normal ligament structure. The study also found that mature ligament cells underwent dedifferentiation, re-entered the cell cycle, and contributed to the regenerated ligament. Single-cell analysis of the regenerating ligament showed that neural-crest-derived mesenchymal cells expressed genes related to the extracellular matrix (ECM), and various immune cells expressed a gene called legumain, which is involved in tissue remodeling. Mutant zebrafish lacking legumain exhibited difficulties in ECM remodeling and efficient ligament regeneration. This research introduces a novel model for scar-free ligament regeneration in adults and highlights the role of communication between immune cells and mesenchymal cells in initiating the tissue’s regeneration.