Molecular aspects of control in epidermal differentiation

Abstract

The mammalian epidermis is organized into layers of structurally different cells—the basal, spinous, granular and cornified layers—which represent steps in the differentiative process that terminates in cornification and desquamation. Investigation of the molecular mechanisms that control this ordered sequence of events provides clues to the etiology of certain epidermal pathologies. DNA synthesis and mitosis are normally restricted to the basal layer. Several substances have been implicated in the mitotic control of epidermal cells, the loss of mitotic activity being the first major step in normal keratinization. Investigations performed in this laboratory indicate that isolated differentiated nuclei can replicate their DNA which they are inhibited from doing in situ. Addition of a high speed supernate from homogenized differentiated cells inhibited this synthetic activity in vitro suggesting the existence of a cytoplasmic inhibitor of DNA synthesis. It is not known whether mitotic inhibition in differentiated epidermal cells is a function of the inhibition of DNA replication.