DERMAL PAPILLA AND THE DEVELOPMENT AND GROWTH OF HAIR 747 The dermal papilla and its influence on ectopic epidermis in ear dermis Cohen (31, 30) and Oliver (35) have shown that the complete whisker bulb region and also papillae with just their own epidermal investments can generate follicles which produce short whiskers when implanted into ear dermis, although the follicles did not develop typical whisker dermal features. Cohen (31, 30, 40) has also implanted whisker dermal papillae alone into ear dermis. He considered that where they contacted ear epidermis they induced the development of ear hair follicles within 14 days, the number of papilla cells being reduced from hundreds down to tens to comply with the normal ear follicle configuration. Adopting a slightly different approach Oliver (41, 42) has made an extended study of the influence of whisker dermal papillae on ectopic epidermis in ear dermis and the collective results will now be considered. Two types of surface epidermis were used, ear epidermis containing follicular epidermal elements and afollicular scrotal sac epidermis, and keratinizing oral epithelium from either the gum or inner lip regions. Small sheets of epidermis or epithelium were obtained by trypsinization and placed basal surface down onto groups of two to six papillae on an ear dermis bed. The implants were then covered by replacing a previously reflected flap of skin and the graft areas biopsied from 7-207 days after operation and serially sectioned. The papillae did not always remain in contact with the grafted epidermis or epithelium and were found isolated in ear dermis, or in contact with ear epidermis at the edge of the implant region, as well as associated with the graft epidermis or epithelium. Approximately 370//0 of the implanted dermal papillae were found isolated in ear dermis. All of these papillae were entirely free of adherent epidermal cells, corroborating the observed absence of such epidermal cells by examination of serial sections of papillae dissected in exactly the same manner ($8). In general they seemed to have maintained approximately their original number of cells, although they were often compacted with a decrease in cellular cytoplasmic volume. Most had acquired a capillary supply and stained with alcian blue. Obviously their integrity was not dependent on contact with epidermal cells. Eighteen dermal papilla/ear epidermis associations were examined. From days 7-21 large alcian blue staining papillae with capillaries had locally induced epidermal hyperplasia, with the epidermis becoming organized as matrices, with suprabasal mitoses, around the papillae. In the single day, 28 specimen vacuolated outer root sheath and an inner root

748 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS sheath containing characteristic trichohyalin granules had also developed, but no other follicular features were present. Between days 35-64, eight follicles induced by single papillae and all producing hair were examined. All were shorter, stouter and had larger bulbs than metanagen ear hair follicles and their papillae contained hundreds of cells compared with the approximately 30-50 present in ear hair follicles (Fig. $). Nevertheless the number of cells incorporated into the papillae of the induced follicles was less than the number present at implantation, accountable in part by the absence of capillaries which are a feature of normal whisker papillae but not of ear hair papillae. Five of the follicles were growing fine non-medullated hairs associated with a thick inner root sheath, while three had thick whisker-like shafts, one at least of which was medullated. Seven of the follicles contained differentiating sebaceous glands but, with the exception of one which opened on to the ear surface, had no sebaceous ducts. The inner root sheath was present at least as far as the ear surface in all of the follicles {Fig. •t), which also showed varying degrees of dermal sheath differentiation but without the development of whisker follicle features. An exception to the developmental sequence outlined above was the presence, at day 63, of a single papilla associated with a matrix at the ear surface which was producing thick laminate keratin. Distinct trichohyalin granules were present at the periphery of the matrix as were some sebaceous cells. With afollicular scrotal sac epidermis whisker dermal papillae were also seen to organize matrices and at day 35 two very large intradermal follicular structures were found, with the usual epidermal elements except sebaceous cells, which were producing hair keratin. Implants of oral epithelium and its own dermis or oral epithelium alone, regardless of whether they formed cysts or became incorporated into the ear surface, showed the preservation of the typically oral pattern of kera- tinization, with the absence of a granular layer and of appendages. This accords with the findings of Billingham and Silvers (23) with tongue and oesophageal epithelium, recombined with ear and sole of foot dermis, in the guinea pig and hamster. In marked contrast a picture of confusion of influence and response was shown by the 22 examples of dermal papilla/oral epithelium associations examined between 24 and 64 days. Contiguous papillary tissue promoted epithelial hyperplasia, with supra- basal mitoses, and epithelial thickening, the basal cells often being highly columnar {Fig. $). Two types of "projections" were seen, one being large