Regulation of cell proliferation in tadpole limb epidermis by thyroxine

The mechanism of thyroxine control of cell proliferation was investigated by studying cell cycle kinetics in limb epidermis of control and thyroxine‐treated Rana pipiens tadpoles using repeated labeling and construction of percent labeled mitoses curves. Changes in labeling index may be attributed primarily to alteration in either the relative length of S in the cell cycle (S/T), or the growth fraction of the cell population. In limb bud epidermis of Stage III tadpoles growth fraction, like labeling index, increased in basal cells but did not change in outer layer after 24 hours of 3, 30 or 300 μg/l thyroxine treatment. Changes in cell cycle parameters, however, were small and similar in both outer and basal layers, and there was no appreciable change in S/T. At Stages IX to XI, changes in labeling index and growth fraction were also parallel. Both parameters increased in intermediate and basal cells but decreased in outer layer after 30 or 300 μg/l thyroxine treatment for 48 hours. In addition, there was a decrease in S/T, due to a lengthening of G1 + ½M and a shortening of S. The cell cycle changes at Stages IX to XI were similar in all layers as at Stage III, regardless of whether labeling index increased or decreased. The results indicate that the specific changes in labeling index observed during thyroxine‐induced growth and differentiation of limb epidermis are linked closely to regulation of size of the proliferative pool, although alterations in cell cycle parameters are of some significance in older tadpoles.