Calcineurin controls proximodistal blastema polarity in zebrafish fin regeneration

Significance Why some animals, but not others, respond to injury with extensive regeneration is an outstanding question and attracts considerable research interest. Planarian flatworms possess a polarity system throughout their anteroposterior axis that specifies the identity of missing tissues at wound sites. The regeneration of vertebrate appendages involves distal growth. However, whether vertebrate appendages can undergo bidirectional regeneration along the proximodistal axis remains unclear. Our study demonstrates that unidirectional blastema regeneration polarity occurs in zebrafish fins along the proximodistal axis. We identified calcineurin as a molecular switch that specifies the blastema of the PCE and controls regeneration polarity in zebrafish fins. Our results are of great importance for future regeneration polarity studies on vertebrates.