Kinetics of cell cycle entry in innervated and denervated forelimb stumps of larval Ambystoma

Pulse and continuous labeling with ³H‐thymidine were used to examine the kinetics of cell cycle entry and progression in innervated, regenerating and denervated, nonregenerating limbs of larval axolotls. In innervated limbs the labeling index (LI) increased from a relatively low level after a pulse (30%) to 60% and 80% after 26 and 50 hr, respectively, of continuous labeling, at both preblastema and blastema stages. Thus a considerably larger proliferative fraction was revealed by continuous labeling data than was predicted from pulse labeling data. Much cycling heterogeneity was shown to exist in the blastema cell population, primarily in the G‐1 phase. These results show that many cells of regenerating limbs are transiently quiescent for periods of up to and perhaps longer than 50 hr. The proliferative fraction in denervated limbs on days 4‐6 postamputation was somewhat less than that of innervated limbs but also larger than predicted from pulse labeling data. The data show that most of the dedifferentiated cells enter the proliferative fraction even in the absence of nerves. Most of these initially cycling cells subsequently leave the proliferative fraction; the LI was less than 20% even after 50 hr of continuous labeling on days 8–10 postamputation.