LR-18

Dermal _-catenin is required for SHH driven hair follicle neogenesis.

Annette Kaminaka, Mayumi Ito, PhD; Chae Ho Lim, PhD

Presented at Symposium on Advanced Wound Care Spring 2021

Hair follicle neogenesis (HFN) occurs in adult skin upon large skin excisions in mice, serving as a rare regenerative model in mammalian wound healing. Nonetheless, wound healing typically results in fibrosis in mice and humans. We previously showed that small skin excisions in mice result in the formation of scar tissue devoid of HFN, displaying features of non-regenerative wound healing, yet experimental SHH activation in wound dermis can induce HFN in such wounds. In this study, we sought to verify the role of dermal Wnt/ _-catenin signaling in HFN, as this pathway is essential for HF development, but is also paradoxically well-characterized in fibrosis in adult wounds. Through utilizing a combined mouse model that simultaneously induces deletion of _-catenin and constitutive activation of Smoothened (Smo) in SM22__+ myofibroblasts, we found that _-catenin is required for SHH-driven dermal papilla (DP) formation that leads to HF regeneration. Additionally, by deletion of _-catenin in large wound SM22__+ myofibroblasts, we show that Wnt/ _-catenin signaling is required for endogenous mechanisms of HFN. Our data suggest that the activation of both WNT and SHH pathways in the skin wound fibroblasts needs to be ensured in future strategies to promote HFN in skin wounds and that Wnt-active fibrotic status may create a permissive state for the regenerative function of SHH.

References

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