Keratinocyte cultures: an experimental model for studying how proliferation and terminal differentiation are co-ordinated in the epidermis

Introduction: the organization of keratinocytesin epidermisThe epidermis is the outer covering of the skin. Itconsists of multiple layers of epithelial cells, keratino-cytes, that are renewed throughout adult life. Prolifer-ating keratinocytes are generally confined to the basal(deepest) layer of the epidermis. Cells that leave thebasal layer have lost the ability to divide and theyundergo terminal differentiation as they move upwardstowards the tissue surface. During terminal differen-tiation the cells change in size, shape and ultrastructur-al appearance, and synthesize a range of new proteins.Keratinocytes at the final stage of terminal differen-tiation, in the outermost epidermal layers, have nonucleus or cytoplasmic organelles; they are full ofkeratin filaments and have an insoluble protein envel-ope (the cornified envelope) closely apposed to theinner surface of the plasma membrane. The accumu-lated layers of terminally differentiated cells at thesurface of the epidermis protect the underlying livinglayers from desiccation and mechanical damage.If we ignore certain important complications (hair,sweat and sebaceous glands, melanocytes, Langerhansand Merkel cells) the epidermis is a simple structureand an ideal tissue in which to investigate a number ofimportant questions of relevance to all renewing tis-sues. These are: (1) What signals control proliferation?(2) What signals trigger the intiation of terminaldifferentiation? (3) What mechanism ensures that thereis a balance between the rate of production of new cellsin the basal layer and the rate of loss of terminallydifferentiated cells from the outermost layers?The development of methods for re-creating humanepidermis in culture (see Watt, 1987, for review) makesthese questions readily amenable to investigation. Inthis article I shall briefly review some of the answersthat are emerging from studies of keratinocytes cul-tures.