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Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision
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Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision
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Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision
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Journal Article
Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision
2016
Overview
Unlike other mammals that must pant or seek shade or water when overheated, humans are able to self-cool to tolerate extreme heat. Sweat glands, which enable humans to run in marathons, are instrumental for this remarkable feat. Lu et al. investigated skin appendage diversity during development of the furry backs and sweaty paws of mice (see the Perspective by Lai and Chuong). They also examined human skin, which is capable of making both hairs and sweat glands in the same area of the body. Epithelialmesenchymal interactions, with varied signaling pathways that act at specific times in development, are key to producing different skin appendages for adaptation to the environment. Science , this issue p. 10.1126/science.aah6102 ; see also p. 1533 Mice and humans exploit the epithelial-mesenchymal circuitry in different ways to direct sweat gland or hair follicle generation. The gain of eccrine sweat glands in hairy body skin has empowered humans to run marathons and tolerate temperature extremes. Epithelial-mesenchymal cross-talk is integral to the diverse patterning of skin appendages, but the molecular events underlying their specification remain largely unknown. Using genome-wide analyses and functional studies, we show that sweat glands are specified by mesenchymal-derived bone morphogenetic proteins (BMPs) and fibroblast growth factors that signal to epithelial buds and suppress epithelial-derived sonic hedgehog (SHH) production. Conversely, hair follicles are specified when mesenchymal BMP signaling is blocked, permitting SHH production. Fate determination is confined to a critical developmental window and is regionally specified in mice. In contrast, a shift from hair to gland fates is achieved in humans when a spike in BMP silences SHH during the final embryonic wave(s) of bud morphogenesis.
