Functional anatomy of the hair follicle: The Secondary Hair Germ

Abstract

The secondary hair germ (SHG)-a transitory structure in the lower portion of the mouse telogen hair follicle (HF)-is directly involved in anagen induction and eventual HF regrowth. Some crucial aspects of SHG functioning and ontogenetic relations with other HF parts, however, remain undefined. According to recent evidence (in contrast to previous bulge-centric views), the SHG is the primary target of anagen-inducing signalling and a source of both the outer root sheath (ORS) and ascending HF layers during the initial (morphogenetic) anagen subphase. The SHG is comprised of two functionally distinct cell populations. Its lower portion (originating from lower HF cells that survived catagen) forms all ascending HF layers, while the upper SHG (formed by bulge-derived cells) builds up the ORS. The predetermination of SHG cells to a specific morphogenetic fate contradicts their attribution to the "stem cell" category and supports SHG designation as a "germinative" or a "founder" cell population. The mechanisms of this predetermination driving transition of the SHG from "refractory" to the "competent" state during the telogen remain unknown. Functionally, the SHG serves as a barrier, protecting the quiescent bulge stem cell niche from the extensive follicular papilla/SHG signalling milieu. The formation of the SHG is a prerequisite for efficient "precommitment" of these cells and provides for easier sensing and a faster response to anagen-inducing signals. In general, the formation of the SHG is an evolutionary adaptation, which allowed the ancestors of modern Muridae to acquire a specific, highly synchronized pattern of hair cycling.

Anagen hair follicle repair: Timely regenerative attempts from plastic extra‐bulge epithelial cells

“…[2] Over the past decades, it is generally assumed that plastic SCs reside only in the bulge and secondary hair germ. [29,30] The presence of SCs or cells with SC-like properties in the lower segment of anagen HFs is supported in part by the fact that cells from this part exhibit colony forming ability, a property of SCs. [42] Recent work in AHFR and physiological anagen unveils the high plasticity of extra-bulge epithelial cells in the outer root sheath and the lower proximal cup, [18,23,53] supporting Chase's hypothesis.…”

“…the two populations of SCs are housed in distinct compartments, with primed SCs in the secondary hair germ and quiescent SCs in the bulge. [27][28][29][30][31] The regeneration from telogen to full anagen was divided into six stages, from anagen I to anagen VI, as defined by Chase et al [32] In anagen I and II, primed SCs in the secondary hair germ are activated first, regenerating the hair bulb and most of the structures in the impermanent lower segment. [27,28,[32][33][34] Quiescent SCs in the bulge are activated later in anagen III to regenerate part of the outer root sheath that lies immediately below the bulge.…”

Do hair follicles operate as primitive, multifocal kidney‐like excretory (mini‐) organs?

“…But how achievable is this really in clinical practice? Exogen requires the prior formation of a club HS that can subsequently be shed and thus that an anagen HF has involuted into a catagen HF and subsequently entered telogen . In order to manipulate the excretory function of HFs, it could be useful to promote human catagen/telogen development.…”

“…Not only forensic scientists, but even the lay public are now well aware of the fact that plucked or cut hair shafts (HS) provide excellent source material for measuring and even timing the past systemic exposure of the human body to drugs (including drugs of abuse) and various toxins, including environmental toxins and heavy metals . Yet, even experts rarely reflect how and why these molecules get into the HS in the first place—and what this tells us about fundamental characteristics of this fascinating, cyclically remodelled mini‐organ …”

“…[1][2][3][4] Yet, even experts rarely reflect how and why these molecules get into the HS in the first place-and what this tells us about fundamental characteristics of this fascinating, cyclically remodelled mini-organ. [4][5][6][7][8][9][10] In this Viewpoint essay, we discuss this often ignored and insufficiently examined key aspect of hair follicle (HF) biology and invite readers to entertain the provocative notion that this finding points to a more fundamentally important, but rarely contemplated function of HFs: to serve as primitive, multifocal excretory (mini-)organs which share surprisingly many functions with kidney physiology.…”