Sustained epithelial β-catenin activity induces precocious hair development but disrupts hair follicle down-growth and hair shaft formation

Abstract

During embryonic and postnatal development, Wnt/␤-catenin signaling is involved in several stages of hair morphogenesis from placode formation to hair shaft differentiation. Using a transgenic approach, we have investigated further the role of ␤-catenin signaling in embryonic hair development. Forced epithelial stabilization of ␤-catenin resulted in precocious and excessive induction of hair follicles even in the absence of Eda/Edar signaling, a pathway essential for primary hair placode formation. In addition, the spacing and size of the placodes was randomized. Surprisingly, the down-growth of follicles was suppressed and hair shaft production was severely impaired. Gene and reporter expression analyses revealed elevated mesenchymal Wnt activity, as well as increased BMP signaling, throughout the skin that was accompanied by upregulation of Sostdc1 (Wise, ectodin) expression. Our data suggest that BMPs are downstream of Wnt/␤-catenin and that their interplay may be a critical component in establishing correct patterning of hair follicles through the reaction-diffusion mechanism.

Cutaneous Retinoic Acid Levels Determine Hair Follicle Development and Downgrowth

“…Recent findings have shown the importance of a dermal ␤-catenin signaling in response to epidermal Wnts as the earliest required events for hf initiation (29). Previously, it was shown that sustained epithelial ␤-catenin induced precocious hair development but led to disrupted hf downgrowth and differentiation (39). The expression results relating to the Wnt/␤-catenin pathway in our Cyp26b1 Ϫ/Ϫ and En1Cre; Cyp26b1f/Ϫ models are particularly interesting because we find up-regulation of several catenins (␣2, ␤1, ␦1, and ␦2), with strikingly significant up-regulation of ␤-catenin in the dermis of En1Cre;Cyp26b1f/Ϫ skin.…”

Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth

“…A Wnt-Shh-Sostdc1 negative feedback loop in tooth patterning In tooth development, it has been reported that Wnt/-catenin signals are upstream of Shh (Kratochwil et al, 2002;Jarvinen et al, 2006;Liu et al, 2008;Närhi et al, 2008) and Sostdc1 (Jarvinen et al, 2006;Närhi et al, 2008;Liu et al, 2008). By contrast, it was also reported that Shh suppresses Wnt/-catenin signaling in early developing mandible (Chamorro et al, 2005;Hendrix et al, 2006;Kratochwil et al, 2002), and the Fgf pathway was suggested as one of major downstream targets of Wnt signaling regulated by Sostdc1 (Ahn et al, 2010).…”

“…Furthermore, sustained epithelial Wnt/-catenin signaling in the hair and teeth of Ctnnb1 (Ex3)fl/+ mice upregulates Shh, Dkk1 and Sostdc1, which suggests that Wnt/-catenin signals are upstream of Shh (Närhi et al, 2008;Liu et al, 2008). Furthermore, deletion of Lef1 or Wnt10b severely diminishes the size and the number of fungiform papillae, and decreases expression of Shh in tongue fungiform papillae (Iwatsuki et al, 2007).…”

“…Ectodermal organs such as teeth, hair, vibrissae and feathers share common morphological features and spatial patterning mechanisms, in which Shh, Wnts and Sostdc1 are key signaling molecules (St-Jacques et al, 1998;Laurikkala et al, 2003;Närhi et al, 2008) but the relationships between these signals are not fully understood. Conditional Shh-and Smo-deficient mice such as K14-Cre;Shh flox/flox and K14-Cre;Smo flox/flox exhibit the same morphological aberrations in tooth patterns: the first (M1) and second (M2) molars are fused and the dental lamina is absent (Dassule et al, 2000;Gritli-Linde et al, 2002).…”

Biology of Human Hair: Know Your Hair to Control It

“…Canonical Wnt/b-catenin signaling plays an important role in HF induction and fate [63][64][65][66][67][68][69], and expression of several Wnts, Wnt ligands and inhibitors is specifically elevated in developing and postnatal HFs [61,[70][71][72]. On the other hand, forced activation of b-catenin signaling promotes HF fate in both embryonic and postnatal skin [67,[73][74][75]. Recent studies also suggest that another pathway, the ectodysplasin signaling pathway, is critical for the induction and maintenance of placode [76,77].…”