Hyperinnervation Inhibits Organ-Level Regeneration In Mammalian Skin

This study investigates the regenerative capabilities of mammalian skin, revealing that while late embryonic skin injuries can regenerate multiple tissue types, this ability is lost after birth due to hyperinnervation in the wound bed. Researchers identified a postnatal wound-specific fibroblast (PWF) population that emerges after birth, which is linked to the inhibition of organ-level regeneration. The study found that overexpression of PWF-enriched genes Timp1, Cxcl12, and Ccl7 in embryonic wounds leads to hyperinnervation. By reducing hyperinnervation through Cxcl12 depletion in fibroblasts or nerve ablation, the researchers were able to restore the skin's ability to regenerate diverse cell types postnatally. This work highlights fibroblast-driven hyperinnervation as a key barrier to regeneration and suggests potential therapeutic targets for enhancing regenerative healing in mammalian skin.