Preparing the hair follicle canal for hair shaft emergence

Abstract

The emergence of hair is a defining event during mammalian skin development, but the cellular mechanisms leading to the opening of the hair follicle canal remain poorly characterized. Our previous studies have shown that early hair buds possess a central column of differentiated keratinocytes expressing Keratin 79 (K79), which marks the future hair follicle opening. Here, we report that during late embryogenesis and early postnatal development, K79+ cells at the distal tips of these columns downregulate E-cadherin, change shape, recede and undergo cell death. These changes likely occur independently of sebaceous glands and the growing hair shaft, and serve to create an orifice for hair to subsequently emerge. Defects in this process may underlie phenomena such as ingrown hair or may potentially contribute to upper hair follicle pathologies including acne, hidradenitis suppurativa and infundibular cysts.

Distinct mechanisms for sebaceous gland self-renewal and regeneration provide durability in response to injury

“…We have previously shown that nascent hair buds generate and extend columns of K79+ differentiated cells out into the epidermis, which subsequently undergo remodeling to form hair follicle openings. 39 , 43 In embryonic (E) day 16.5 skin, we observed K79+ columns in developing hair buds, as expected, but no PPARγ expression ( Figure 1F ). By E17.5, however, we noticed basal PPARγ expression, reminiscent of the K5+PPARγ+ transitional basal cells seen in adult follicles ( Figure 1F ).…”

Hair follicles modulate skin barrier function

“…Concordantly, studies in ichq mice, which develop ichthyotic features due to a mutation in Cst6 , have also found that disease onset coincides with the emergence of hair 49,50 . These and other findings support the notion that the formation of the hair canal—an event characterized by extensive cellular remodeling, as well as shifts in immune and microbial composition—represents a seminal but also potentially vulnerable event in skin development 19,51,52 .…”

“…These and other findings support the notion that the formation of the hair canal-an event characterized by extensive cellular remodeling, as well as shifts in immune and microbial composition-represents a seminal but also potentially vulnerable event in skin development 19,51,52 .…”

Basic principles of hair follicle structure, morphogenesis, and regeneration

“…In the mature HF, keratin (KRT)79+ cells line the inner surface of the infundibulum. 60,103 These general developmental stages occur during the morphogenesis of all hair types, but it has been shown in mice and Cashmere goats that the induction of different HF types (eg, primary and secondary HFs) occurs at different embryonic stages (eg, mouse awl and auchene hairs at E16.5 and zig zag hair around P0) and that their development is tuned by the interplay of different molecules. 17,94 The disturbance of the finely tuned HF morphogenesis at any level may result in congenital alopecia.…”