Punctuated cell cycling in the regeneration blastema of urodele amphibians: An hypothesis

We previously assumed that all cells in the regeneration blastema are randomly distributed throughout the cell cycle and actively cycling towards the next mitotic division. We now show that data from continuous labeling (³H-thymidine) experiments do not support this view and favor instead the hypothesis that the blastema cell cycle is punctuated in the g₁ phase wherein cells can enter what we term a transiently quiescent (TQ) position. We call this hypothesis the punctuated cycling (PC) hypothesis. We further propose that the relative sizes of the quiescent and actively cycling populations explain (1) variations in rates of regeneration in different sizes of urodele amphibians, (2) the rate and success of regeneration in different species, and (3) how various controlling factors, such as injury, nerves, growth factors, wound epidermis, and hormones, influence the initiation and progression of the regeneration process. This PC hypothesis is important for interpreting previous pulse labeling data, is consistent with recently obtained continuous labeling data, and is experimentally testable.