Cell multiplication enabled a repair-ready state in salamander hearts

In experiments in Pleurodeles waltl salamanders, researchers used multicolour labels to track cells in the epicardium, the heart’s outer cell layer. After injury, these cells briefly multiplied before their descendants accumulated at the injury site.

The team depleted certain claudins, proteins in junctions that seal neighbouring cells together, while leaving those junctions otherwise intact. This altered the layer’s organisation and mechanical state, impaired cell multiplication and reduced cells’ ability to detach. Their descendants then failed to activate a regeneration-related pattern of gene activity or complete the transition into migrating cells. These migrating cells were needed to shape material between cells that supported outward extensions from heart-muscle cells at the injury site. The findings indicated that activation alone was insufficient for regeneration.