Reciprocal requirements for EDA/EDAR/NF-kappaB and Wnt/beta-catenin signaling pathways in hair follicle induction.
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.
Zhang
Yuhang
Y
Departments of Dermatology and Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Tomann
Philip
P
Andl
Thomas
T
Gallant
Natalie M
NM
Huelsken
Joerg
J
Jerchow
Boris
B
Birchmeier
Walter
W
Paus
Ralf
R
Piccolo
Stefano
S
Mikkola
Marja L
ML
Morrisey
Edward E
EE
Overbeek
Paul A
PA
Scheidereit
Claus
C
Millar
Sarah E
SE
Schmidt-Ullrich
Ruth
R
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism; D053331:Ectodysplasins / Q000235:genetics / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018859:Hair Follicle / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D053338:Receptors, Ectodysplasin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D012867:Skin / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000099176:Noggin Protein
D002352:Carrier Proteins; D053331:Ectodysplasins; D016328:NF-kappa B; D053338:Receptors, Ectodysplasin; D051153:Wnt Proteins; D051176:beta Catenin; D000099176:Noggin Protein; C506019:Eda protein, mouse