62 KERATIN AND KERATINIZATION 



bring about the epithelial pattern. Their, as yet unstabilized, free, external 

 surfaces produce a selection of responses from what we have termed the 

 " cell's surface repertoire." The establishment of a definite surface layer 

 encloses the other cells in a different environment which diverts them 

 toward synthesizing different products (mesenchymal substances), which 

 in their turn react with the inner surfaces of the basal layer cells to form 

 the basal membrane and to induce local variations in the epidermal layer. 

 By their subsequent development these epidermal variations make return 

 demands for food and support on the underlying layers leading to the 

 building up of a dermal organization of fibrillar scaffolding and supply 

 vessels. 



The molecular basis of these events is ill understood and their discussion 

 is often marred by vague concepts which in effect conceal our ignorance. 

 Further discussion of the problem will be found in Chapter 3. 



There is much evidence, emphasized by Montagna, Chase and colleagues 

 (Montagna, 1956) and by Billingham (1958), to show that the determination 

 is not irrevocable and that the cells of the germinal layer itself remain 

 effectively multipotential. In many animals, hairs may normally become 

 differentiated from basal layer cells throughout life and Billingham cites 

 the extraordinary case of the hairy velvet covering the growing horns 

 of deer which is in its entirety reformed annually. Further, after losses due 

 to many injuries (wounds, burns, X-radiation) many epidermal elements 

 regenerate from the remaining basal layer cells or from cells of the outer 

 root sheath of the hair follicle (Montagna, 1956; Billingham, 1958). 



Other evidence of persistent multipotency is provided by the epithelia 

 of many internal surfaces which may exhibit a cyclic metaplasia under 

 hormonal control with a well defined physiological function. These may 

 be of endodermal origin, but since they may be capable of keratin 

 formation, they are relevant here. The best-known example is that of 

 the vaginal epithelium which oscillates between mucin and keratin 

 production, cells of a contrasted cytology being produced successively 

 by the same basal layer (Nilsson, 1959) (Fig. 59). In other situations 

 keratin production oscillates with glycogen (Hinglais-Guillard, 1959). 



Thus it would still seem that the course of differentiation followed by a 

 cell leaving the basal layer is determined by effects emanating from 

 neighbouring cells and from the underlying dermis. That in grafts cells 

 may retain the characteristics of their site of origin could be due to the 

 fact that large numbers of cells are transferred in a graft and, in effect, 

 carry with them their original environment. When a denuded area is 

 merely " seeded " with small groups of cells, the new growths are said to 

 be typical of the new site rather than the old (Montagna, 1956). 



In many malignant tumours arising from epithelial surfaces (carcinomas) 

 the normal controls maintaining a stable differentiation seem relaxed and 



