APOPTOSIS IN HUMAN SKIN DEVELOPMENT - MORPHOGENESIS, PERIDERM, AND STEM-CELLS

During human skin development, embryonic- and fetal-specific periderm cells and incompletely keratinized cells are replaced by keratinocytes that differentiate while stratifying to form the fully functional epi dermis. Proliferating basal cells of fetal skin also develop into epid ermal appendages such as hair follicles and glands. We demonstrate tha t programmed cell death, not emphasized in conventional epidermal biol ogy, has an important function in establishing the final architecture of the human epidermis and its appendages. Immunohistochemical localiz ation of transglutaminases in fetal periderm, intermediate epidermal c ells, and within appendages coincides with DNA fragmentation indicatin g that apoptosis is involved in deletion of these stage-specific cells and remodeling of appendages. The data also suggest that terminal dif ferentiation of epidermal cells might be a specialized form of apoptos is. The pattern of expression of bcl-2, a gene associated with surviva l of some cells, is exclusive of the distribution patterns of markers of the cell death pathway. Bcl-2 protein is correlated with specific m orphogenetic events in hair follicles and eccrine sweat glands, and it s presence in single cells of the hair follicle bulge suggests that Bc l-2 may be a stem cell marker. (C) 1994 Wiley-Liss, Inc.