Fig. 6

Hh activation can convert fibrotic Wnt-active dermal cells into DP in wounds. a–d Axin2-CreER; R26-SmoM2 (Axin2-SmoM2) and littermate controls were subjected to SW and treated with TAM from PW1d until tissue harvest at PW30d (n = 9–15 W (3–5 M) per condition). Whole-mount HFN assay (a) and quantifications (b, c). H&E and immunohistochemical analyses with indicated markers (d). e Tracing of tomato-labeled Axin2⁺ cells in Axin2-CreER; R26-Tomato (Axin2-Tom). Axin2-Tom mice were subjected to LW and treated with TAM from PW3d until PW12d (before complete re-epithelialization). Tissue was harvested at PW23d and stained with anti-RFP antibody. f Model: Conversion of wound repair to regeneration in adult skin. Wound healing in mammalian skin typically results in scarring and lack of appendage regeneration. Dermal Hh activation can install de novo dermal papilla into wounds, resulting in regenerative HF neogenesis, despite collagen deposition in adult wounds. n: number of wounds (W) or mice (M), Data are represented as mean ± s.d., **p < 0.01, ***p < 0.001; Student’s t-test, Dashed white circle: wound boundary, Dashed line: epidermis–dermis border, SW small wound, LW large wound, PW post-wound, DP dermal papilla, AP alkaline phosphatase, FE follicular epithelium, HF hair follicle, Scale bars represent 500 µm (a), 10 μm (d, e)