Fig. 3. Comparison of cellular mechanisms that govern hair follicle progression through anagen as put forth by the bulge activation hypothesis and the hypothesis of hair follicle predetermination. (A) The bulge activation hypothesis states that the initial event of anagen is the direct activation of a bulge-localized stem cell population by follicular papilla signaling (yellow arrow). The resultant proliferation of bulge cells (black arrow) is the source of all hair follicle layers and of both the downward growth of the hair follicle and the upward growth of the hair shaft and inner root sheath (IRS). (B) The hypothesis of hair follicle predetermination proposes that anagen activation is a two-step process that includes the initial activation of hair germ cells (1) and consequent activation of bulge-localized cells (2). The activity of the hair germ cells results in the formation of the ascending hair follicle layers, including the IRS and hair shaft (white arrow), whereas proliferation of the bulge-localized cells produces the outer root sheath (black arrow).