Chapter 2 49 Keratin bundles inside each cell are physically cross-linked, thereby conferring the structure of the HS with great strength and flexibility as it grows and emerges from the skin surface. Histologically, anagen follicles are long and straight, but they are angled inside skin to allow the HS to lay flat on the body surface. The length of the HS is determined by the duration of anagen as well as the proliferation and differentiation potential of matrix cells in the hair bulb.39 Mature hair follicles undergo regular cycles of regeneration and destruction throughout life, fueled by the regenerative capacity of follicular stem cells, which reside in the bulge area.40 Each individual hair cycle is divided into three phases: anagen (growth phase), catagen (regression phase), and telogen (resting phase).41 As shown in Figure 4, at the onset of anagen (anagen I) signals from the DP stimulate the division of matrix cells, and the inductive properties of the DP are maintained by signals from the follicular epithelium. During anagen I to anagen VI, matrix cells in the hair bulb proliferate and differentiate to form the IRS and HS. During catagen, the lower two-thirds of the follicle undergoes apoptosis and the hair follicle regresses. While the initial wave of hair follicle cycling in mice is highly synchronized moving in an anterior- to-posterior direction, the ensuing hair follicle cycles are only Figure 4 Schematic representation of the hair follicle growth cycle E: epidermis S: sebaceous gland B: bulge DP: dermal papilla ORS: outer root sheath IRS: inner root sheath HS: hair shaft HB: hair bulb M: matrix. Image courtesy of Dr. Sarah Millar.