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

Wnt/beta-catenin and NF-kappa B 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 P-catenin activity. We find that Wnt/beta-catenin signaling is absolutely required for NF-kappa B activation, and that Edar is a direct Wnt target gene. Wnt/beta-catenin signaling is initially activated independently of EDA/EDAR/NF-kappa B activity in primary hair follicle primordia. However, Eda/Edar/NF-kappa B 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-kappa B signaling, providing a molecular explanation for the latter observation, and identify Wnt10b as a direct NF-kappa B target. These data reveal a complex interplay and interdependence of Wnt/beta-catenin and EDA/EDAR/NF-kappa B signaling pathways in initiation and maintenance of primary hair follicle placodes.