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
Departments of Dermatology and Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Dev Cell. 2009 Jul;17(1):49-61. doi: 10.1016/j.devcel.2009.05.011.
Wnt/beta-catenin and NF-kappaB 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/beta-catenin signaling requires epithelial beta-catenin activity. We find that Wnt/beta-catenin signaling is absolutely required for NF-kappaB activation, and that Edar is a direct Wnt target gene. Wnt/beta-catenin signaling is initially activated independently of EDA/EDAR/NF-kappaB activity in primary hair follicle primordia. However, Eda/Edar/NF-kappaB signaling is required to refine the pattern of Wnt/beta-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-kappaB signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-kappaB target. These data reveal a complex interplay and interdependence of Wnt/beta-catenin and EDA/EDAR/NF-kappaB signaling pathways in initiation and maintenance of primary hair follicle placodes.
Wnt/β-连环蛋白和核因子κB信号传导机制在发育和疾病过程中发挥着核心调控作用，但这两条信号通路如何相互作用尚不清楚。我们以毛囊诱导作为模型系统，发现真皮Wnt/β-连环蛋白信号的模式形成需要上皮β-连环蛋白的活性。我们发现Wnt/β-连环蛋白信号是核因子κB激活所绝对必需的，并且Edar是Wnt的一个直接靶基因。在初级毛囊原基中，Wnt/β-连环蛋白信号最初独立于EDA/EDAR/核因子κB活性被激活。然而，Eda/Edar/核因子κB信号对于优化Wnt/β-连环蛋白活性模式以及在基板发育后期维持该活性是必需的。我们发现Wnt10b和Wnt10a局部表达的维持需要核因子κB信号，这为后一观察结果提供了分子解释，并确定Wnt10b是核因子κB的一个直接靶标。这些数据揭示了Wnt/β-连环蛋白和EDA/EDAR/核因子κB信号通路在初级毛囊基板起始和维持过程中的复杂相互作用和相互依赖性。
