Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
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DOI：
10.1016/j.devcel.2009.05.011
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发表时间：
2009-07
影响因子：
11.8
通讯作者：
Schmidt-Ullrich, Ruth
中科院分区：
文献类型：
--
作者：
Zhang, Yuhang;Tomann, Philip;Andl, Thomas;Gallant, Natalie M.;Huelsken, Joerg;Jerchow, Boris;Birchmeier, Walter;Paus, Ralf;Piccolo, Stefano;Mikkola, Marja L.;Morrisey, Edward E.;Overbeek, Paul A.;Scheidereit, Claus;Millar, Sarah E.;Schmidt-Ullrich, Ruth
Wnt/β-Catenin和NF-κB信号机制在发育和疾病中提供中央控制，但这些通路如何相交尚不清楚。以毛囊诱导为模型系统，我们证明了真皮WNT/β-连环蛋白信号的图案化需要上皮β-连环蛋白活性。我们发现Wnt/β-catenin信号是核因子-κB激活所必需的，并且Edar是一个直接的Wnt靶基因。WnT/β-连环蛋白信号最初在初级毛囊原基中被激活，与EDA/EDAR/NF-κB活性无关。然而，需要EDA/EDAR/NF-κB信号来完善WNT/β-连环蛋白的活性模式，并在胎盘发育的后期维持这种活性。我们发现WNT10b和WNT10a的定位表达的维持需要NF-κB信号，为后一种观察提供了分子解释，并确定WNT10b是直接的NF-κB靶标。这些数据揭示了WNT/β-连环蛋白和EDA/EDAR/NF-κB信号通路在初级毛囊安慰剂的启动和维持过程中的复杂相互作用和相互依赖。
Wnt/β-catenin and NF-κB signaling mechanisms provide central controls in development and disease, but how these pathways intersect is unclear. Using hair follicle induction as a model system, we show that patterning of dermal Wnt/β-catenin signaling requires epithelial β-catenin activity. We find that Wnt/β-catenin signaling is absolutely required for NF-κB activation, and that Edar is a direct Wnt target gene. Wnt/β-catenin signaling is initially activated independently of Eda/Edar/NF-κB activity in primary hair follicle primordia. However, Eda/Edar/NF-κB signaling is required to refine the pattern of Wnt/β-catenin activity, and to maintain this activity at later stages of placode development. We show that maintenance of localized expression of Wnt10b and Wnt10a requires NF-κB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-κB target. These data reveal a complex interplay and inter-dependence of Wnt/β-catenin and Eda/Edar/NF-κB signaling pathways in initiation and maintenance of primary hair follicle placodes.
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