Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing.

Nat Commun. 2018 Nov 21;9(1):4903. doi: 10.1038/s41467-018-07142-9.
Hedgehog stimulates hair follicle neogenesis by creating inductive dermis during murine skin wound healing.
Lim CH1, Sun Q1, Ratti K1, Lee SH1, Zheng Y2, Takeo M1, Lee W1, Rabbani P1, Plikus MV3, Cain JE4, Wang DH5, Watkins DN6, Millar S2, Taketo MM7, Myung P8, Cotsarelis G2, Ito M9.

Mammalian wounds typically heal by fibrotic repair without hair follicle (HF) regeneration. Fibrosis and regeneration are currently considered the opposite end of wound healing. This study sought to determine if scar could be remodeled to promote healing with HF regeneration. Here, we identify that activation of the Sonic hedgehog (Shh) pathway reinstalls a regenerative dermal niche, called dermal papilla, which is required and sufficient for HF neogenesis (HFN). Epidermal Shh overexpression or constitutive Smoothened dermal activation results in extensive HFN in wounds that otherwise end in scarring. While long-term Wnt activation is associated with fibrosis, Shh signal activation in Wnt active cells promotes the dermal papilla fate in scarring wounds. These studies demonstrate that mechanisms of scarring and regeneration are not distant from one another and that wound repair can be redirected to promote regeneration following injury by modifying a key dermal signal.

Full Study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249328/