Apoptosis in human skin development: Morphogenesis, periderm, and stem cells

Abstract

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 epidermis. Proliferating basal cells of fetal skin also develop into epidermal appendages such as hair follicles and glands. We demonstrate that programmed cell death, not emphasized in conventional epidermal biology, has an important function in establishing the final architecture of the human epidermis and its appendages. Immunohistochemical localization of transglutaminases in fetal periderm, intermediate epidermal cells, and within appendages coincides with DNA fragmentation indicating that apoptosis is involved in deletion of these stagespecific cells and remodeling of appendages. The data also suggest that terminal differentiation of epidermal cells might be a specialized form of apoptosis. The pattern of expression of bcl-2, a gene associated with survival of some cells, is exclusive of the distribution patterns of markers of the cell death pathway. Bcl-2 protein is correlated with specific morphogenetic events in hair follicles and eccrine sweat glands, and its presence in single cells of the hair follicle bulge suggests that Bcl-2 may be a stem cell marker.

Telomerase activity in a specific cell subset co-expressing integrinβ1/EGFR but not p75NGFR/bcl2/integrin β4 in normal human epithelial cells

“…Although the distributions of cellular compartments in the various epithelia di er slightly, quite similar epithelial cell subsets could be distinguished by the di erential expressions of some ubiquitous marker proteins such as integrins, EGFR, p75 NGFR and bcl-2 (our unpublished results). A similar observation has been made in human epidermal basal cells in which p75 NGFR -expressing basal cells reside overlapping with the expression of bcl-2 (Polakowska et al, 1994). According to the physical locations of p75 NGFR -positive cells, it is reasonable to characterize them as reserve cells which are most typically identi®able at the morphologic level in squamous/columnar (S/C) junction (so-called transformation zone) in the uterine cervix as well as in junction regions of the stomach and esophagus (Ohta et al, 1997 and our unpublished observations).…”

“…These results led us to conclude that cellular characteristics of p75 NGFR -expressing cells are similar to that of reserve cells noted in various epithelial basal layer. A number of previous studies agree that bcl-2 acts against cell proliferation, cell death, apoptosis and di erentiation in many normal cell types (Buck et al, 1987;Sariola et al, 1991;Polakowska et al, 1994;Reed, 1994 for a review; Harada et al, 1998). In this context, the p75 NGFR -expressing basal cell subset is distinct from a specialized cell type committed toward terminal di erentiation.…”

“…Alternatively, it is possible that p75 NGFR is expressed only in progenitor cells and down-regulated shortly after cell division. To further characterize the p75 NGFR -expressing cells, the fractionated cells were examined for the expression of bcl-2 which is known as a factor for the promotion of cell survival (Polakowska et al, 1994;Reed, 1994). The p75 NGFR -positive cells were puri®ed to up to 90% homogeneity from 1.0 6 10 6 primary NCC and NCE cells by the DAB method as described ( Figure 5A).…”

The Effect of Estrogen on Bone Marrow-Derived Rat Mesenchymal Stem Cell Maintenance: Inhibiting Apoptosis Through the Expression of Bcl-xL and Bcl-2

“…4). These results are in correlation with other studies performed on other stem cells like skin stem cells, HSCs, and epithelial stem cells where apoptosis and members of the bcl-2 family of genes were shown to be important in the differentiation and regulatory pathways [38][39][40]. When we cultured MSCs in the presence of estrogen, the expression of anti-apoptotic Bcl-2 and Bclx L were increased.…”

Jag2‐Notch1 signaling regulates oral epithelial differentiation and palate development

“…During mouse embryogenesis, periderm cells first appear at late E9 on the forelimb buds and, over the next 3-4 days, periderm cells emerge from the single-layered epithelium at many locations to cover the entire embryo (Holbrook and Odland, 1975;M'Boneko and Merker, 1988). This cell layer is transient and undergoes apoptosis late in gestation (Holbrook and Odland, 1975;Polakowska et al, 1994). Several functions have been proposed for this cell layer, including protection from the environment (Hayward, 1983), regulation of underlying mesenchyme (Scott et al, 1987), and contribution to cornified envelope formation (Akiyama et al, 1999), but all of these functions have yet to be proven.…”