Chapter 2 51 cycle. During telogen, the DP sits right underneath the bulge, which allows direct interactions between bulge stem cells and the DP. The proximity between the bulge and the DP is maintained throughout telogen. Recently there are reports demonstrating that telogen can be divided into two phases: a refractory phase that is resistant to hair follicle growth stimuli and is characterized by up-regulation and activation of Bmp2/4, and a competent phase in which bulge stem cells become highly sensitive to anagen-inducing signals. In the competent phase, Bmp signaling is counteracted with the Wnt/β- catenin signaling to reach its optimal activity in early anagen. This cyclic regulation of activities of activators and inhibitors must remain synchronized with the autonomous, intra-follicular “hair clock” to control individual hair follicle cycles.44 Following telogen, follicular stem cells in the bulge are activated to initiate the new anagen.45 The transition from telogen to anagen for hair regeneration shares many molecular similarities with embryonic morphogenesis of hair placodes. The molecular interaction between epithelial stem cells and the DP is believed to be essential to initiate new anagen. Only after a critical concentration of molecules promoting hair growth is reached can epithelial stem cells be activated, and subsequently the hair follicle enters anagen phase. The new follicle forms adjacent to the old pocket that holds the hair club. The telogen club hair can remain in its canal for several cycles, thereby contributing to the density of the coat, even when the new HS exits through the same orifice. While external forces can force old HS out passively, shedding is mainly an active process, which is normally named exogen.46 The molecular mechanisms that drive hair follicle cycling remain of great interest and mystery, although many molecular regulators have been identified through the investigation of mouse mutants with defects in hair follicle cycling, and by gene expression profiling of epthelial stem cells at each hair cycle stage. Wnt/β-catenin, Noggin, and Shh act as anagen-inducing signals, while Bmp have been implicated in inhibition of stem cell activation and follicle differentiation.47-49 Fgf5 is a key inducer of catagen as demonstrated