Volar fibroblast–keratinocyte signaling pathways

The volar fibroblast–keratinocyte signaling pathway is a specialized paracrine communication system that determines the unique physiological characteristics of glabrous (non-hairy) skin found on the palms and soles (Yamaguchi et al., 2004, J Cell Sci). This pathway is primarily driven by the secretion of Dickkopf-1 (DKK1) by volar dermal fibroblasts, which acts as a potent antagonist of the Wnt/beta-catenin signaling pathway in overlying keratinocytes (Yamaguchi et al., 2008, Gene). The suppression of Wnt signaling in these keratinocytes induces the expression of volar-specific markers, such as Keratin 9 (KRT9), and results in a thickened stratum corneum and the absence of hair follicles (Rognoni et al., 2016, Exp Dermatol). Dysregulation of this signaling axis is implicated in various skin disorders, including palmoplantar keratodermas and the site-specific development of acral lentiginous melanoma (Choi et al., 2014, J Invest Dermatol). While not a single drug target, components of this pathway, particularly DKK1 and the Wnt signaling cascade, are being explored for therapeutic intervention in wound healing and oncology (DKN-01 clinical trials). This signaling network highlights the importance of mesenchymal-epithelial interactions in maintaining tissue-specific identity and homeostasis.

Other names

Palmoplantar fibroblast-keratinocyte crosstalkDKK1-Wnt signaling axis in skinGlabrous skin signaling pathway

Modulation of the Wnt/beta-catenin pathway via DKK1 secretion from dermal fibroblasts to influence keratinocyte differentiation and regional skin identity.