Abstract
Wound‐induced hair follicle neogenesis (WIHN) describes a regenerative phenomenon in adult mammalian skin wherein fully functional hair follicles regenerate de novo in the center of large excisional wounds. Originally described in rats, rabbits, sheep, and humans in 1940−1960, the WIHN phenomenon was reinvestigated in mice only recently. The process of de novo hair regeneration largely duplicates the morphological and signaling features of normal embryonic hair development. Similar to hair development, WIHN critically depends on the activation of canonical WNT signaling. However, unlike hair development, WNT activation in WIHN is dependent on fibroblast growth factor 9 signaling generated by the immune system's γδ T cells. The cellular bases of WIHN remain to be fully characterized; however, the available evidence leaves open the possibility for a blastema‐like mechanism wherein epidermal and/or dermal wound cells undergo epigenetic reprogramming toward a more plastic, embryonic‐like state. De novo hair follicles do not regenerate from preexisting hair‐fated bulge stem cells. This suggests that hair neogenesis is not driven by preexisting lineage‐restricted progenitors, as is the case for amputation‐induced mouse digit tip regeneration, but rather may require a blastema‐like mechanism. The WIHN model is characterized by several intriguing features, which await further explanation. These include (1) the minimum wound size requirement for activating neogenesis, (2) the restriction of hair neogenesis to the wound's center, and (3) imperfect patterning outcomes, both in terms of neogenic hair positioning within the wound and in terms of their orientation. Future enquiries into the WIHN process, made possible by a wide array of available skin‐specific genetic tools, will undoubtedly expand our understanding of the regeneration mechanisms in adult mammals.
Highlights
The hair follicle (HF), a defining anatomical feature of all mammals, is an intricate mini-organ composed of epithelial and mesenchymal cells that work in concert to generate a hair shaft
Embryonic-like regeneration is prevalent in nonmammalian vertebrates, and two principal regenerative responses can be distinguished based on the cellular mechanism: (1) regeneration from lineage-restricted, tissue-specific stem cells, and (2) regeneration via lineage reprogramming, such as in the process of dedifferentiation−redifferentiation
Neither was recognized at the time as Wound-induced hair follicle neogenesis (WIHN), de novo regeneration of HFs was first observed in adult rats by Dann et al (1941) following excisional wounding and by Taylor (1949) following full-thickness skin cryo-injury
Summary
The hair follicle (HF), a defining anatomical feature of all mammals, is an intricate mini-organ composed of epithelial and mesenchymal cells that work in concert to generate a hair shaft. Principles and mechanisms of hair follicle neogenesis upper portion and a transient lower portion, and within the permanent portion of the HF lies its slow cycling stem cells, known as bulge stem cells (Cotsarelis et al 1990; Morris et al 2004; Tumbar et al 2004; Snippert et al 2010) The progeny of these stem cells divide rapidly and generate all the lower HF’s structures, including the hair shaft (Taylor et al 2000; Morris et al 2004). The adult HF can efficiently “rebuild” after micro-injury, partial amputation, and even complete amputation (Fig. 1), making it a valuable model for studying cellular and signaling mechanisms of injury-induced regeneration in mammals
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