Hair follicle predetermination

Recent genetic and molecular studies of hair follicle (HF) biology have pro vided substantial insight; however, the molecular data, including expressio n patterns, cannot be properly appreciated without an understanding of the basic cellular rearrangements and interactions that underpin HF cyclic tran sformations. We present a novel interpretation of the major cellular proces ses that take place during HF cycling - the hypothesis of hair follicle pre determination. This hypothesis is an extension of previous models of HF cel lular kinetics but has two critical modifications: the dual origin of the c ycling portion of the HF, and the timing of the recruitment of stem cells. A compilation of evidence suggests that the ascending portion of the HIT (h air shaft and inner root sheath) arises not from bulge-located HF stem cell s that contribute to the formation of only the outer root sheath (ORS), but instead from the germinative cells localized in the secondary hair germ. I n middle anagen, upon completion of the downward growth of the HF, cells de rived from the bulge region migrate downward along the ORS to reside at the periphery of the HF bulb as a distinct, inactive cell population that has specific patterns of gene expression - 'the lateral disc'. These cells surv ive catagen-associated apoptosis and, under the direct influence of the fol licular papilla (FP), transform into the hair germ and acquire the ability to respond to FP signaling and produce a new hair. Thus, we propose that th e specific sensitivity of germ cells to FP signaling and their commitment t o produce the ascending HIT layers are predetermined by the previous hair c ycle during the process of transformation of bulge-derived lateral disc cel ls into the secondary hair germ.