Heat-shock protein 60 is required for blastema formation and maintenance during regeneration

Zebrafish fin regeneration requires the formation and maintenance of blastema cells. Blastema cells are not derived from stem cells but behave as such, because they are slow-cycling and are thought to provide rapidly proliferating daughter cells that drive regenerative outgrowth. The molecular basis of blastema formation is not understood. Here, we show that heat-shock protein 60 (hsp60 ) is required for blastema formation and maintenance. We used a chemical mutagenesis screen to identify no blastema (nbl ), a zebrafish mutant with an early fin regeneration defect. Fin regeneration failed innbl due to defective blastema formation.nbl also failed to regenerate hearts. Positional cloning and mutational analyses revealed thatnbl results from a V324E missense mutation inhsp60 . This mutation reducedhsp60 function in binding and refolding denatured proteins.hsp60 expression is increased during formation of blastema cells, and dysfunction leads to mitochondrial defects and apoptosis in these cells. These data indicate thathsp60 is required for the formation and maintenance of regenerating tissue.