Characterisation of human hair follicle development

Abstract

Humans have a characteristic distribution of hair across the body. Visible, relatively long and thick terminal hair fibres are present on the scalp and eyebrows in childhood, and are stimulated to grow on other parts of the body, such as the beard and armpits, by hormones during puberty. The short and fine vellus hairs, in contrast, are not readily visible and cover most of the body, including the face. Here we report quantification of the timing and characteristics of hair follicle development in human embryogenesis, from gestational Weeks 8–19, and compare this to mouse hair follicle development. We find that human hair follicles develop first on the head, where we identify several distinct initiation sites, followed by the torso. Clustered follicular units are produced by secondary hair follicles budding off the epidermis from sites close to earlier-forming primary follicles. Arrector pili muscles are detected from gestational Week 17. Although terminal and vellus hair follicles have clear differences in the adult, both hair types initially develop from placodes and dermal condensates of similar size. Once their development is initiated, we find that human hair follicles grow and mature at the same rate, regardless of anatomical location, but have different density at different body sites. These findings demonstrate that regional differences in hair characteristics of human skin, such as the distinction between scalp and forehead, are largely caused by processes that act after the initial stages of hair follicle morphogenesis. Efforts to understand the evolution of human ‘hairlessness’ should, therefore, focus on genetic and cellular events that take place after hair follicle morphogenesis. We compared human skin appendages, including eccrine sweat glands, with those in mouse. We found that molecular markers, such as EDA, EDAR, SOX2 and WNT pathway components, are broadly similar in expression between both species, although species-specific differences do exist. Notably, SOX2 expression, which distinguishes different hair follicle types in the mouse, is detected in all human hair follicle types, though with a later onset of expression than that observed in mouse. Together with comparison of morphology and gene expression, these results support the use of embryonic mouse primary hair follicles as a model for human hair follicle development.