Mechanism of Hair Loss from the Point of View of Epidermal Cell Polarity

Abstract

The epidermis and hair follicle epithelium have a polarized stratified architecture, and epidermal homeostasis is maintained by stem cell and progenitor populations present in the basal layer of the interfollicular epidermis and in different compartments of the hair follicle. Atypical protein kinase Cs (aPKCs-a subgroup of the PKC family) are localized to tight junctions and regulate the apico-basal epithelial polarity in simple epithelia. In the stratified epidermis, aPKCs are expressed in the basal layer and are implicated in the regulation of oriented cell division by localizing to the apical pole of basal cells during mitosis. Mutant mice harboring epidermis-specific deletion of aPKCλ showed progressive hair loss, abnormal hair cycling, an increase of asymmetric cell division in the epidermis and hair follicles, and a gradual decrease in the hair follicle stem cell (HFSC) population. Lineage tracing analysis has demonstrated that mutant HFSCs lose their stemness and become more committed proliferating progenitors. Moreover, the expressions of quiescence-inducing factors (Bmp6 and Fgf18) were suppressed in the mutant hair follicles. These results clarify a novel function of aPKCλ in maintaining the quiescence of HFSCs and suggest that epidermal cell polarity is a new clue to understanding the pathogenesis of hair loss.