An updated classification of hair follicle morphogenesis

Abstract

Hair follicle (HF) formation in developing embryonic skin requires stepwise signalling between the epithelial epidermis and mesenchymal dermis, and their specialized derivatives, the placode/germ/peg and dermal condensate/papilla, respectively. Classically, distinct stages of HF morphogenesis have been defined, in the mouse model, based on (a) changes in cell morphology and aggregation; (b) expression of few known molecular markers; (c) the extent of follicle downgrowth; and (d) the presence of differentiating cell types. Refined genetic strategies and recent emerging technologies, such as live imaging and transcriptome analyses of isolated cell populations or single cells, have enabled a closer dissection of the signalling requirements at different stages of HF formation, particularly early on. They have also led to the discovery of precursor cells for placode, dermal condensate and future bulge stem cells that, combined with molecular insights into their fate specification and subsequent formation, serve as novel landmarks for early HF morphogenetic events and studies of the signalling networks mediating these processes. In this review, we integrate the emergence of HF precursor cell states and novel molecular markers of fate and formation to update the widely used 20‐year‐old seminal classification guide of HF morphogenetic stages by Paus et al. We then temporally describe the latest insights into the early cellular and molecular events and signalling requirements for HF morphogenesis in relation to one another in a holistic manner.

Single-cell transcriptome profiling reveals dermal and epithelium cell fate decisions during embryonic hair follicle development

“…During hair follicle development the dynamic morphological changes have been extensively studied (Paus et al, 1999; Saxena et al, 2019a; Schmidt-Ullrich and Paus, 2005). In mice, in utero hair follicle development has been histologically categorized into three unique stages: induction (E13.5 - E14.5), organogenesis (E15.5 - 17.5), and cytodifferentiation (E18.5 onwards) (Schmidt-Ullrich and Paus, 2005).…”

“…In mice, in utero hair follicle development has been histologically categorized into three unique stages: induction (E13.5 - E14.5), organogenesis (E15.5 - 17.5), and cytodifferentiation (E18.5 onwards) (Schmidt-Ullrich and Paus, 2005). More recently, with the development of single-cell RNA sequencing (scRNA seq), new intermediate cell states during early hair follicle morphogenesis have been delineated and an updated classification of different hair follicle stages has been reported (Mok et al, 2019; Saxena et al, 2019a). Seminal works have delineated that reciprocal signaling pathways between epithelial and dermal cell populations play vital roles during hair follicle morphogenesis (Lee and Tumbar, 2012; Millar, 2002; Rishikaysh et al, 2014; Sennett and Rendl, 2012).…”

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

“…Several articles in this issue study skin morphogenesis during development. Rendl's group provides a refined classification guide to hair follicle morphogenesis . It builds upon the seminal morphological guide proposed two decades ago by Paus et al, and incorporates new molecular‐level knowledge from recent single‐cell RNA‐sequencing studies .…”

“…Rendl's group provides a refined classification guide to hair follicle morphogenesis. [33] It builds upon the seminal morphological guide proposed two decades ago by Paus et al, [34] and incorporates new molecular-level knowledge from recent single-cell RNA-sequencing studies. [35,36] The study by Wong's group reports on the role of GATA6 in regulating maintenance of the uppermost hair follicle compartment, [37] while another study explores the F I G U R E 1 Skin morphogenesis across developmental, regenerative and evolutionary levels.…”

New developments in hair research

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| INTRODUC TI ONThe hair follicle is a highly complex organ, the biology [1,2] and chemistry [3,4] of which has greatly exercised the minds of scholars, including some of the greatest minds (see below). [5] Consequently, the field of hair research has progressively expanded over the years.

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