FIGURE 1. Defining refractory and competent telogen.

a, Propagation (blank arrows) of hair regenerative waves is seen in Msx2-null mice (also see Supplementary Fig. 1). Similar patterns can be seen in normal black mice after hair clipping. Roman characters, anagen stages; T, telogen. b, Under physiological conditions, some domains can become refractory to the spreading wave (white arrow). c, Normal telogen timing in C57BL/6J mice. The durations of anagen and telogen were measured in 22 hair-cycle domains from dorsal and ventral skin. Error bars represent standard deviation; n = 18, 22, 28 and 30, from left to the right. Min. and Max. represent the range of values, whereas numbers at the bottom represent average (Aver.) number of days. d, Experimental induction of refractory telogen with cyclosporine A. The x coordinate represents the timescale (in days) when experiments began in the early telogen of the non-treated skin region. Cyclosporine A was applied to a localized region (treated, Tx) during early telogen, and induced new anagen about 8 days later. The surrounding non-treated refractory telogen skin (Non Tx) remained in telogen. When the non-treated skin was at day 19 of telogen, treated Tx skin had already proceeded to the late stage of its induced new anagen (left panel, day 19). When non-treated skin was at day 24 of telogen, the cyclosporine-treated region had finished its induced new anagen phase and had entered new telogen (middle panel, day 24). Soon, the non-treated skin progressed into competent telogen. At day 34, the non-Tx region entered its natural anagen. The regenerative wave spread but could not enter the Tx region because it was still in its refractory telogen period (right panel, day 37). Black, anagen; green, competent telogen; red, refractory telogen. e, In female mice, multiple hair-cycle domains were reset into one after pregnancy/lactation. Arrowheads, time sequence. f, Delayed response to plucking during refractory telogen. Tel., telogon. Hair plucking/regeneration was used to gauge the competent and refractory telogen status (n = 16). The minimum time (shown in days) represents the time required for new pigmented hair filaments to be visible. This time is shorter when more hairs were plucked or when the same number of hairs was plucked in the competent period.