Epidermal-Derived Hedgehog Signaling Drives Mesenchymal Proliferation During Digit Tip Regeneration

September 2021 in “ Journal of Clinical Medicine ”

Zeshaan N. Maan, Yuval Rinkevich, Janos A. Barrera, Kellen Chen, Dominic Henn, Deshka S. Foster, Clark A. Bonham, Jagannath Padmanabhan, Dharshan Sivaraj, Dominik Duscher, Michael S. Hu, Kelley S. Yan, Michael Januszyk, Michael T. Longaker, Irving L. Weissman, Geoffrey C. Gurtner

hedgehog signaling sonic hedgehog SHH Wnt signaling hair follicle differentiation epidermal tissues mesenchymal tissues

TLDR Epidermal signaling helps regenerate fingertip tissue.

The study examined the role of epidermal-derived Hedgehog (HH) signaling in mesenchymal proliferation during digit tip regeneration in mice. It found that while Wnt and HH signaling were confined to epidermal tissues, HH signaling also influenced mesenchymal tissues, particularly stromal fibroblasts and bone, indicating a mechanism of epidermal-mesenchymal crosstalk. The research identified 287 differentially expressed genes, with 84 upregulated in regenerating digit tips, linked to regenerative phenotypes such as hair follicle regeneration. Experiments with transgenic mice and in vitro assays showed that Sonic Hedgehog (SHH) signaling stimulated mesenchymal progenitor proliferation, enhancing regeneration. The study, involving 6 mice per group, suggested that understanding these pathways could improve therapeutic outcomes for tissue repair in mammals.