Selective migration of terminally differentiating cells from the basal layer of cultured human epidermis.

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Abstract
How terminally differentiating cells are selectively expelled from the basal layer of epidermis was studied in culture, using involucrin synthesis as an early marker of terminal differentiation in human keratinocytes. When keratinocytes are forced to grow as a monolayer by reducing the Ca ion concentration of the culture medium, they still begin to synthesize involucrin. Raising the level of Ca ions induces stratification, and cells that are synthesizing involucrin are selectively expelled from the basal layer. During Ca induced stratification no new proteins or glycoproteins are synthesized, and the rate of cell division does not change. Movement of involucrin-positive cells out of the basal layer was unaffected by cycloheximide, tunicamycin or cytosine arabinoside. Keratinocytes growing as a monolayer already apparently have the necessary properties to determine their position when stratification is induced. Addition of Ca simply allows formation of desmosomes and other intimate cell contacts required for stratification. The properties of involucrin-positive cells that determine their suprabasal position include a reduced affinity for the culture substrate and preferential adhesion to other cells at the same stage of terminal differentiation. The molecular basis of these adhesive changes is discussed.