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Reciprocal Requirements for EDA/EDAR/NF-κB and Wnt/β-Catenin Signaling Pathways in Hair Follicle Induction

2009; Elsevier BV; Volume: 17; Issue: 1 Linguagem: Inglês

10.1016/j.devcel.2009.05.011

1878-1551

Yuhang Zhang, Philip Tomann, Thomas Andl, Natalie M. Gallant, Joerg Huelsken, Boris Jerchow, Walter Birchmeier, Ralf Paus, Stefano Piccolo, Marja L. Mikkola, Edward E. Morrisey, Paul A. Overbeek, Claus Scheidereit, Sarah E. Millar, Ruth Schmidt‐Ullrich,

Wnt/β-catenin signaling in development and cancer

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 interdependence of Wnt/β-catenin and EDA/EDAR/NF-κB signaling pathways in initiation and maintenance of primary hair follicle placodes.