An Updated Classification of Hair Follicle Morphogenesis.

Hair follicle formation in developing embryonic skin requires stepwise signaling between the epithelial epidermis and mesenchymal dermis, and their specialized derivatives, the placode/germ/peg and dermal condensate/papilla, respectively. Classically, distinct stages of hair follicle morphogenesis have been defined, in the mouse model, based on 1) changes in cell morphology and aggregation, 2) expression of few known molecular markers, 3) the extent of follicle downgrowth, and 4) 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 signaling requirements at different stages of hair follicle 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 hair follicle morphogenetic events and studies of the signaling networks mediating these processes. In this review, we integrate the emergence of hair follicle precursor cell states and novel molecular markers of fate and formation to update the widely used 20-year old seminal classification guide of hair follicle morphogenetic stages by Paus and colleagues. We then temporally describe the latest insights into the early cellular and molecular events and signaling requirements for hair follicle morphogenesis in relation to one another in a holistic manner. This article is protected by copyright. All rights reserved.