Apoptosis coordinates with proliferation and differentiation during human hair follicle morphogenesis

Abstract

Apoptosis sculptures the most complicated skin appendage, feathers, out of epidermal layers by playing a variety of roles (1). Human hair follicle formation is different from feathers in growth direction and pattern formation of proliferative zone. To delineate the apoptotic events together with proliferation and differentiation in developing human hair follicle and emphasis on the mechanism and biological meaning of epidermal hair canal. We used TUNEL to examine apoptosis and Ki-67, involucrin, filaggrin immuno-localization to examine proliferation and differentiation. In hair germs, apoptosis was diffuse in periderm, basal keratinocytes, and mesenchymal cells with high Ki-67 expression, but spared follicular germinative cells with low Ki-67 and high bcl-2 expression. In hair pegs, apoptosis was active in high Ki-67 expression area, like outer root sheath, hair follicle sheath, but spared dermal papilla with low Ki-67 and high bcl-2 expression. In bulbous pegs, apoptosis appeared in companion layer, precortical area, inner root sheath and outer root sheath, but spared bulge area with high bcl-2 expression. Apoptosis resulted in epidermal and subepidermal hair canal formation. Filaggrin and involucrin were expressed in the lining cells of hair canal. CD1a+ cells were densely distributed alone the hair canal before its opening. During human hair follicle morphogenesis, apoptosis coordinates with proliferation to shape the growth zone, creates space to free the hair shaft from follicular wall, and directs a driving force on hair shaft extension. Apoptosis accompanies the terminal differentiation of epidermal hair canal. The bottom becomes interfollicular epidermis after roof shedding and hair exposure. Langerhans cells also populate in the hair canal before its opening. The biological meaning of epidermal hair canal is supposed to prepare the barrier when hair perturbing the intact of epidermis.