Programmed cell death in terminally differentiating keratinocytes: role of endogenous endonuclease.

Mammalian epithelium is a tissue with a very high turnover rate. It consists of a rapidly proliferating compartment comprising basal and suprabasal keratinocytes, from which cells move upwards while differentiating into granular keratinocytes. The end product is shed as an enucleate corneocyte, which has a mechanically rigid, chemically resistant cross-linked keratinous envelope. The loss of the nucleus occurs specifically in the granular keratinocyte layer; here, cells with the classical apoptotic morphology of clumped and marginated condensed chromatin may be observed. This morphology is characteristic of "programmed" cell death in other systems, of which the lymphocyte has been most extensively studied, and is associated with the cleavage of nuclear DNA into nucleosome-sized fragments. In the present investigation we separated newborn mouse skin into basal and granular keratinocyte fractions and examined the state of the DNA in each fraction. Our results indicate that cells in the basal layer, while their DNA is perfectly intact, are preparing to die. DNA fragmentation is initiated in the granular keratinocyte layer and is identical in pattern to that seen in other examples of programmed cell death.