A comprehensive guide for the recognition and classification of distinct stages of hair follicle morphogenesis.

The response of embryonic mouse dental epithelium and mesoderm to tissues of ectopic origin was examined. Isolated molar or incisor mesoderm was confronted with epithelium isolated from the plantar surface of the embryonic mouse foot plate or from the snout. Harmoniously structured teeth were formed from the foot epithelium and incisor or molar mesoderm. These data are interpreted as an unequivocal demonstration of the inductive role of the dental mesenchyme. Teeth were absent in confrontations of dental mesenchyme and snout epithelium. The presence of hair follicles in these explants is described and discussed with reference to other integumental epithelio-mesenchymal interactions. Dental epithelium forms keratinizing surface-like epithelium and invading bands of epithelium in association with foot mesoderm; definitive structures are not formed. On the other hand, when incisor or molar epithelium is associated with snout mesoderm, hair follicles are seen in addition to keratinizing surface-like epithelial configurations. The roles of the epithelial and mesenchymal tissues and the nature of epithelio-mesenchymal interactions in the developing mouse integument are discussed.

Tissue interactions in embryonic mouse tooth germs: II. The inductive role of the dental papilla

It is generally agreed that the dermal papilla is a vital component of the hair and feather follicle. Lillie & Wang (1941, 1944) and Wang (1943) have shown for feather follicles that if the dermal papilla, which normally maintains its integrity throughout the growth cycles, and its ectodermal investment are removed from the follicle, feather production ceases. However, if a dermal papilla is transplanted into these ‘deprived’ follicles, renewed feather growth is induced. An inductive property is also ascribed to the dermal papilla of the hair follicle (Chase, 1955; Cohen, 1961). Chase has suggested that in the hair follicle the dermal papilla retains its integrity throughout the growth cycles and induces renewed follicle activity at the end of telogen. However, relatively little experimental work has been performed on the dermal papilla of the hair follicle to determine the exact role of the papilla in follicle maintenance and hair growth.

Whisker growth after removal of the dermal papilla and lengths of follicle in the hooded rat.

Epimorphin : a mesenchymal protein essential for epithelial morphogenesis

Expression and the role of E- and P-cadherin in the histogenesis of the surface epidermis and hair follicles were examined using the upper lip skin of the mouse. P-cadherin is expressed exclusively in the proliferating region of these tissues, that is in the germinative layer of the surface epidermis, the outer root sheath and the hair matrix. E-cadherin is coexpressed in these layers but this molecule was also detected in non-proliferating regions such as the intermediate layer of the surface epidermis and the immature regions of the inner root sheath. Neither P- nor E-cadherin was detected in fully keratinized layers such as the horny layer of the surface epidermis, the outermost layer of the outer root sheath and the mature hair fibres. These two cadherins were not detected in dermal cells. We cultured pieces of the upper lip skin in vitro in the absence or presence of a monoclonal antibody to E-cadherin (ECCD-1) or to P-cadherin (PCD-1). In control cultures, skin morphogenesis normally occurred in a pattern whereby the hair follicles grew and dermal cells were condensed to form the dermal sheath. A mixture of ECCD-1 and PCD-1, however, induced abnormal morphogenesis in the skin in several respects. (1) The cuboidal or columnar arrangement of basal epithelial cells was distorted. (2) Hair follicles were deformed. (3) Condensation of dermal cells was suppressed, causing a homogeneous distribution of these cells. These results suggest that cadherins present in epidermal cells are involved not only in maintaining the arrangement of these cells but also in inducing dermal condensation.

Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis.

Hair is recognized as one of the most sensitive indicators of bodily health in man and animals; but, although we know that many factors in heredity and environment affect the formation and growth of hair, we do not understand how they act. We need first of all to find out which effects are due to direct action on the skin and which are secondary to other physiological changes. For this reason, great interest centers on experimental methods of modifying the environment of skin. Skin grafting is a valuable tool in the analysis of hair follicle behavior, and use has been made of autografts,\" homografts,3 and even interspecific grafts.4* I t is not yet possible to obtain permanent homografts of adult skin.6 Two important advantages are obtained by removing the skin to an even more unnatural environment, a tissue culture chamber: first, the complexities of a continually changing blood supply are avoided, and second, the day by day observation of living follicles is made possible. Two kinds of hairs have received attention from those who attempted to cultivate skin and hair follicles in evitro. They are the tactile hairs, or vibrissae, which are found in most mammals on the face and a t other specific sites, and the pelage hairs, which cover the general body surface. The vibrissae are larger and more specialized hairs with a sensory function?' They are usually the first to develop in the embryo, and this gives them some advantages as material for tissue culture. Although intermediate forms do OCCUT,~ it is easy in practice to distinguish vibrissae from pelage hairs. It is well known that the tissues from embryos will differentiate more readily in vitro than will those of adults, and, for that reason, the study of hairs in tissue culture began with embryonic skin. Strangewayslo was the first to do this. She reported in a short note that pelage hair follicles from guinea pig embryos underwent a little development in tissue culture, but that vibrissa follicles gave more satisfactory results. Murray\" indicated in an abstract that she had cultivated the vibrissa follicles of rat embryos and obtained good differentiation and hair production. Both authorslo, Is were less successful with the later developing pelage hair follicles, and attributed their failure to the thickening and keratinization of the epidermis, which discouraged further development of the follicles. HardyI3 explanted skin from the trunk of mouse embryos, and this tissue underwent all the stages of normal follicle differentiation, which led to the production of keratinized pelage hairs. This development was observed in

Margaret H. Hardy

Papers

The development of pelage hairs and vibrissae from skin in tissue culture.