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 beta-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.