032 The Hypothesis of Hair Follicle Predetermination

Andrei A. Panteleyev1, Colin A.B. Jahoda2, and Angela M. Christiano1. 1Departments of Dermatology and Genetics & Development, Columbia University New York, NY; 2Department of Biological Science, Univ. of Durham, Durham, UK

Despite a substantial progress in genetic and molecular studies of hair follicle (HF) biology, the molecular data, including expression patterns, cannot be properly appreciated without understanding the basic cellular rearrangements and interactions that maintain HF cyclic transformations. Here, we present a further attempt to understand the interaction between different HF cell populations and outline the major cellular processes that take place during its cyclic progression through periods of growth, regression, and quiescence. The Hypothesis of Hair Follicle Predetermination, as put forth here, represents an extension of the previous models of HF cellular kinetics with one critical modification: the timing of the recruitment of HF stem cells. The patterns of cell proliferation during anagen-telogen transition, together with morphological evidence, suggest that there are two separate cell populations with proliferation potential in the late telogen HF: the cells of the bulge region (stem cells) and the hair germ. Further, based on our studies of the hairless phenotype in mice, immunohistochemistry data, and extensive analysis of the recent literature, we provide evidence to suggest that the activity of hair germ cells is the initiating event of anagen, which precedes the activity of the cells in the bulge region. The hair germ cells give rise to the ascending part of the growing HF, including the hair shaft and IRS, while the downgrowing ORS is a product of the bulge (stem) cell activity. Thus, the mature anagen HF has a dual origin. During anagen, some cells with clonogenic potential migrate from the bulge region along the ORS and reside on the hair bulb periphery. During catagen, these cells get into direct contact with follicular papilla and undergo a process of “maturation” (follicular papilla-guided formation of hair germ), thus acquiring the ability to respond to follicular papilla signaling and produce a plurality of ascending layers of the new HF. In conclusion, we suggest that the growth characteristics of the HF and hair shaft are predetermined by the previous hair cycle, during the recruitment of stem cells from the bulge region and consequent process of hair germ formation.