在汗腺与毛发命运决定中，间充质-上皮信号传导的时空拮抗作用。
Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision.
作者信息
Lu Catherine P, Polak Lisa, Keyes Brice E, Fuchs Elaine
机构信息
Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
Howard Hughes Medical Institute, Chevy Chase, MD, 20815-6789, USA.
出版信息
Science. 2016 Dec 23;354(6319). doi: 10.1126/science.aah6102.
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.
有毛身体皮肤中汗腺的增加使人类能够跑马拉松并耐受极端温度。上皮-间充质相互作用对于皮肤附属器的多样模式形成至关重要，但其特化背后的分子事件仍 largely 未知。通过全基因组分析和功能研究，我们表明汗腺由间充质来源的骨形态发生蛋白（BMPs）和成纤维细胞生长因子特化，这些因子向上皮芽发出信号并抑制上皮来源的音猬因子（SHH）产生。相反，当间充质 BMP 信号传导被阻断时，毛囊得以特化，从而允许 SHH 产生。命运决定局限于一个关键的发育窗口，并且在小鼠中是区域特化的。相比之下，在人类中，当 BMP 在芽形态发生的最后胚胎波期间激增使 SHH 沉默时，就实现了从毛发到腺体命运的转变。
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