Functional anatomy of the hair follicle: The Secondary Hair Germ

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