DERMAL PAPILLA AND THE DEVELOPMENT AND GROWTH OF HAIR 745 In the feather follicle Lillie and Wang (24, 25) and Wang (26), using tissue removal and implantation procedures, demonstrated that the dermal papilla is a permanent structural feature which periodically induces the growth of feathers. In progressive contrast to the work of Dhouailly (13, 14) on the embryo, they also seemed to demonstrate that tract specificity (the factors responsible for the type of feather which grows) is solely determined by the site of origin of the epidermis which invests the dermal papilla. Thus adult feather epidermis apparently provides another example of an intrinsically determined epidermis. Furthermore the dermal papilla was unable to induce feather growth when implanted into the superficial half of a follicle or under extrafollicular epidermis. Similarly, although not directly demonstrated, several authorities for various reasons thought that the dermal papilla is also primarily responsible for the growth of hair (27-31). In order to investigate this, and other inter- active possibilities, Cohen (31) devised techniques for the exposure and individual dissection of the comparatively large whisker follicles on the upper lip of the rat. THE ADULT RAT WHISKER FOLLICLE AS AN EXPERIMENTAL MODEL FOR INVESTIGATING DERMAL--EPIDERMAL INTERACTIONS IN HAIR GROWTH The basic structure of the whisker follicle in the rat has been described by Vincent (32). It is a large highly innervated hair follicle, serving a tactile function, which produces hair in a cyclic manner but with little shortening of the follicle associated with the very brief catagen phase (33). The dermal component is conspicuously represented by an outer collagenous capsule enclosing a blood sinus system and, surrounding the greater length of the epidermal component, the mesenchymal layer which is confluent with the dermal papilla (Fig. 1). This unique morphology is apparently an exaggeration and specialization of the structural elements present in the simplest of follicles to which the whisker follicle is anatomically related through a series of follicle types (34). Regeneration of the derreal papilla Simulating the work of Lillie and Wang (24-26), Oliver (33, 35) re- moved dermal papillae from the bases of whisker follicles and found that

746 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS hair growth ceased. However after a short lag period derreal papillae of apparently normal size were regenerated and whiskers of normal length were grown. Even when the complete bulb region and up to the lower third of the follicle were removed, smaller than normal dermal papillae regener- ated and generations of short whiskers were produced. These papillae regenerated at the level of tissue removal and were not accompanied by a lengthening of the follicle. It was further found that the greater the length of follicle removed the shorter were the whiskers subsequently grown. Although papilla regeneration and whisker growth did not occur where more than the lower third of the follicle was removed, the remaining part persisted. The mesenchymal layer, the outer root sheath, and their glassy mem- brane interface were identified as the essential prerequisites for this re- generation phenomenon since segments of the follicle wall, provided that their proximal ends derived from within the lower third of the follicle, regenerated papillae and produced whiskers when implanted into ear dermis (36). The new papillae apparently developed from cells from the mesenchymal layer. The preservation of the tubular nature of the implants was also shown to be important because when they were incised longitudinally, opened out and implanted as sheets they were unable to organize follicles and degenerated (37). The derreal papilla and the induction of hair growth Failure of papilla regeneration in the upper two thirds of the follicle, while in itself an intriguing finding, nevertheless enabled the strongly suspected inductive property of the dermal papilla to be tested. Dermal papillae, completely free of contaminating epidermal matrix cells, were implanted into the bases of the superficial halves of follicles after removal of their lower halves (38). Where the papillae remained in position the growth of generations of shorter than normal whiskers ensued. An important difference was observed in these follicles when compared with those which regenerated papillae after tissue removal. Associated with the induction of bulb formation and whisker growth the follicle grew in length as it does during anagen in the normal pelage hair cycle (Fig. 2). Cells from the implanted papilla were also seen to contribute to the mesen- chymal layer over the newly grown length of follicle. As a logical extension of these results the influence of whisker dermal papillae on epidermis of non-whisker origin was studied.