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Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.


ABSTRACT: 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.

SUBMITTER: Lu CP 

PROVIDER: S-EPMC5333576 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.

Lu Catherine P CP   Polak Lisa L   Keyes Brice E BE   Fuchs Elaine E  

Science (New York, N.Y.) 20161201 6319


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 epithelia  ...[more]

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