Dermal β-Catenin Is Required for Hedgehog-Driven Hair Follicle Neogenesis

Area of Science:

• Regenerative medicine
• Dermatology
• Developmental biology

Background:

• Mammalian wound healing typically results in fibrosis, not regeneration.
• Hair follicle neogenesis (HFN) is a rare regenerative event observed in large skin wounds in mice.
• Previous studies indicated hedgehog (Hh) pathway activation can induce HFN in non-regenerative wounds.

Purpose of the Study:

• To investigate the role of dermal Wnt/β-catenin signaling in HFN.
• To determine if Wnt/β-catenin signaling is necessary for Hh-induced HFN.
• To elucidate the interplay between Wnt/β-catenin and Hh pathways in wound regeneration.

Main Methods:

• Utilized mouse models with targeted deletion of β-catenin in myofibroblasts.
• Employed a combined mouse model for simultaneous β-catenin deletion and Smoothened activation.
• Performed transcriptome analysis on dermal papilla cells.

Main Results:

• Wnt/β-catenin signaling is essential for endogenous HFN mechanisms.
• β-catenin is required for Hh-driven dermal papilla formation.
• Both Wnt/β-catenin and Hh pathways are activated in dermal papilla cells during HFN.

Conclusions:

• Dermal Wnt/β-catenin signaling is indispensable for hair follicle neogenesis.
• A Wnt-active fibrotic environment may facilitate Hh-mediated regeneration.
• Future strategies for promoting HFN should target the activation of both Wnt and Hh pathways in skin wound fibroblasts.