DERMAL PAPILLA AND THE DEVELOPMENT AND GROWTH OF HAIR 743 from typical long and spindle shaped fibroblasts to rounded cells containing organelles associated with protein synthesis (7, 8). Division products in the developing epidermal matrix region, which invests the dermal papilla, give rise to the various cylindrical elements which comprise the inner root sheath, the first to differentiate, and the hair itself. ECTODERMAL--MESODERMAL INTERACTIONS IN THE DEVELOPMENT OF SKIN APPENDAGES Tissue separation and recombination studies, using ectoderm and mesoderm of the same and differing embryonic ages and from the same and differing anatomical sites, have demonstrated that interactions occur between these elements to ensure the development of skin and appendages in mammals and birds (9-18). Intensive studies of avian skin have established that the mesoderm initially dictates the developmental fate of the overlying ectoderm, while itself showing regional variations in its specificity and the timing and "strength" of its influence (9-11). However in certain instances committed and differentiating ectoderm may then not only become increasingly or totally resistant to the influence of "foreign" mesoderm, but may also be capable of organizing such mesoderm to comply with the developmental course the ectoderm had already embarked upon. Thus recombinants of prospective feather ectoderm and scale mesoderm, from the leg, either developed feathers and scales or feathers alone (11, 12). Dhouailly (13, 14) has further shown that the gross features character- istic of a feather type are determined by the dermis while the fine structure of the barbules is determined by the epidermis. Moreover the mesoderm also largely determines the time of appearance of the teleoptiles (juvenile feathers) as well as the mode of replacement of the neoptiles {"embryo" feathers). In general, so far as the less extensive experimental appraisal allows, an essentially similar situation seems to be true of mammalian skin in relation to the development of hairs (and teeth). Jacobson (15) presented evidence for two interactive crises in the development of whisker follicles in the mouse one at the time of follicle site determination and a later one between the dermal papilla and the follicle epidermis. Recombinants of mesoderm from the lip region, in which whisker follicles normally develop, with foot plate ectoderm or with tooth ectoderm developed whiskers (16,

744 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS 17). However recombinants of lip mesoderm with ectoderm from the back, where pelage hairs normally develop, showed no follicle development while lip ectoderm recombined with back mesoderm or tooth mesoderm developed whiskers (17, 18). It is probably worthwhile at this point to seek some explanation for the variations in influence and response described above, and those to be referred to later, within the embryological concepts of induction, determin- ation and differentiation (19, 20). Briefly, induction describes the action of one population of cells on another which causes them to change in a developmentally significant way (20). One resultant of an inductive act is determination which can be envisaged as the process whereby a progressive and permanent blocking of part of the genome occurs in a cell population so that its developmental potential is restricted (20). In this way, for example, epidermal cells have been permanently set apart from mesodermal cells so that they can enjoy mutually exclusive specific syntheses (e.g. keratin and myoglobin pro- duction). However epidermal cells also exhibit a wide range of synthetic activities, including the production of keratin (in all its varieties), sebum, mucus and enamel, exactly which being dependent on, and an expression of, their differentiated state. Where the differentiated status of an epidermal cell population is changed (or "modulated") on exposure to extrinsic factors, we know that it was not rigidly determined. In those few instances where epidermal modulation has not been demonstrated there is still the possibility that the epidermal population has not been exposed to factors capable of changing its gene activity in a marked way (21-23). Even where modulation occurs, a further problem then arises as to whether this repre- sents differential use of the remaining unblocked genome by a system of gene repression, or relative rates of gene function (20). ADULT SKIN AND APPENDAGES In adult mammals Billingham and Silvers (21-23) have shown that the superficial epidermis is capable of being modulated its thickness and pattern of keratinization being dependent on regionally specific stimuli from the underlying dermis. However oral epithelia appeared to be in- trinsically determined, resisting the influence of "foreign" dermis. Hair and feather follicles, in their anatomy, behaviour and products, are more complicated than the surrounding skin and accordingly seem to yield more complicated experimental results.