Epidermal β-Catenin Activation Remodels the Dermis via Paracrine Signaling to Distinct Fibroblast Lineages

The study demonstrated that sustained epidermal Wnt/β-catenin signaling led to the expansion of the stem cell compartment and the formation of ectopic hair follicles, accompanied by fibroblast proliferation and ECM remodeling in the dermis. It was found that epidermal Hedgehog (Hh) and Transforming growth factor-beta (TGF-β) signaling mediated these dermal changes. Inhibition or deletion of these pathways prevented the β-catenin-induced dermal reprogramming and ectopic follicle formation. Specifically, epidermal Shh stimulated the proliferation of papillary fibroblasts, while TGF-β2 influenced the proliferation, differentiation, and ECM production of reticular fibroblasts. The study concluded that the dermal response to epidermal Wnt/β-catenin signaling was dependent on distinct fibroblast lineages responding to different paracrine signals.