Fig. 1. The hair cycle. In mammals, including humans, hairs do not persist but are periodically shed and re-grown in a ‘hair cycle’. Hair follicle (HF) cycling is associated with substantial structural reorganization of the HF itself – the complex epithelial sac that also contains a mesenchymal compartment (follicular papilla; FP) at its base. The HF consists of a permanent (upper) portion and a cycling lower portion that undergoes cycles of complete destruction and restoration. The stages of HF regression (catagen) and growth (anagen) are separated by the resting phase – telogen. The uppermost portion of the telogen follicle (the infundibulum) shares many structural and functional features with the interfollicular epidermis. Its lower margin is demarcated by the sebaceous gland duct. The attachment of the arrector pili muscle to the HF epithelium demarcates the bulge region, which is prominent in human (especially embryonic) HFs but is barely visible in the mouse. The induction of anagen is associated with a burst of proliferation in the lower portion of the telogen follicle. According to current views – in particular, the bulge activation hypothesis – the source of this proliferation is the HF stem cell population located in the bulge region (Cotsarelis et al., 1990). The nature of the anagen inductive signal and its source are still debated. With progression of early anagen proliferation, the HF grows downward and completely engulfs the FP, which also undergoes substantial structural changes. At this point, the prominent upward flow of epithelial cells is formed; these originate from the hair matrix, where active proliferation takes place. Proliferation of hair matrix cells results in the formation of the hair shaft (comprising three layers: medulla, cortex and hair cuticle) and inner root sheath (IRS; comprising three layers: cuticle, Huxley’s layer and Henle’s layer). The ascending HF layers are encased by the outer root sheath (ORS). The epithelial compartment of the anagen HF is surrounded by the dermal sheath, a structure of mesenchymal origin that is contiguous with the FP. The entire HF structure is encapsulated by a perifollicular connective tissue sheath. Anagen HFs (depending on their functional type) are associated with complex vascular and neural networks. Anagen lasts approximately two weeks in mice and up to 4-5 years in humans. With the transition to catagen, the lower HF portion undergoes apoptosis-driven diminution, and the hair bulb shrinks. The FP condenses and travels upward along with the regressing lower epithelial portion. It comes into direct contact the lower part of the overlying permanent portion of the HF. Interdigitation and specific patterns of keratinization of the hair shaft cells and cells of the ORS form the club hair, which anchors the hair shaft in the follicle.