title: 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.
authors.affiliation: Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Lu
authors.affiliation: Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Polak
authors.affiliation: Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Brice E
authors.initials: BE
authors.lastname: Keyes
authors.affiliation: Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA. fuchslb@rockefeller.edu.|Howard Hughes Medical Institute, Chevy Chase, MD, 20815-6789, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004439:Eccrine Glands / Q000196:embryology* / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D018859:Hair Follicle / Q000196:embryology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008648:Mesoderm / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D015398:Signal Transduction; D013542:Sweat; D060449:Wnt Signaling Pathway
chemical_list: D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins