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 etal. 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.