Regional Control of Hairless versus Hair-Bearing Skin by Dkk2
Regional Control of Hairless versus Hair-Bearing Skin by Dkk2
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DOI：
10.1016/j.celrep.2018.11.017
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发表时间：
2018-12-11
期刊：
影响因子：
8.8
通讯作者：
Millar, Sarah E.
中科院分区：
文献类型：
--
作者：
Song, Yaolin;Boncompagni, Ana C.;Millar, Sarah E.
有毛的皮肤是哺乳动物的一个决定性特征。然而，一些特殊的皮肤区域，例如人类的手掌、脚底和腹侧手腕以及小鼠足底，是完全无毛的。使用小鼠足底皮肤作为模型系统，我们发现内源性分泌型 Wnt 抑制剂 DKK2 抑制足底毛囊发育并允许无毛皮肤的形成。足底皮肤保留了毛囊发育所需的所有机械成分，因为 Dkk2 的基因缺失允许形成功能齐全的足底毛囊，从而产生外部毛发，包含皮脂腺和干细胞室，并进行再生生长。在缺乏 Dkk2 的情况下，Wnt/β-catenin 信号传导活性最初在胚胎足底皮肤中广泛升高，并逐渐形成图案，模仿正常毛发区域的毛囊发育。这些数据提供了一个范例，其中 Wnt 抑制剂的区域限制性表达是无毛皮肤与有毛皮肤的规范基础。
Haired skin is a defining characteristic of mammals. However, some specialized skin regions, such as human palms, soles and ventral wrist, and mouse plantar foot, are entirely hairless. Using mouse plantar skin as a model system, we show that the endogenous secreted Wnt inhibitor DKK2 suppresses plantar hair follicle development and permits the formation of hairless skin. Plantar skin retains all of the mechanistic components needed for hair follicle development, as genetic deletion of Dkk2 permits formation of fully functional plantar hair follicles that give rise to external hair, contain sebaceous glands and a stem cell compartment, and undergo regenerative growth. In the absence of Dkk2, Wnt/beta-catenin signaling activity is initially broadly elevated in embryonic plantar skin and gradually becomes patterned, mimicking follicular development in normally haired areas. These data provide a paradigm in which regionally restricted expression of a Wnt inhibitor underlies specification of hairless versus hairy skin.