Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.

Zhang Y, Tomann P, Andl T, Gallant NM, Huelsken J, Jerchow B, Birchmeier W, Paus R, Piccolo S, Mikkola ML, Morrisey EE, Overbeek PA, Scheidereit C, Millar SE, Schmidt-Ullrich R
Dev Cell. 2009 17 (1): 49-61

PMID: 19619491 · PMCID: PMC2859042 · 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.

MeSH Terms (19)

Animals beta Catenin Carrier Proteins Cell Differentiation Ectoderm Ectodysplasins Embryo, Mammalian Female Gene Expression Regulation, Developmental Genes, Reporter Hair Follicle Mice Mice, Transgenic NF-kappa B Pregnancy Receptors, Ectodysplasin Signal Transduction Skin Wnt Proteins

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