Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dish - SCAD). We observe that injury triggers a swarming-like collective cell migration of fascia fibroblasts that progressively contracts the skin and form scars. Swarming is exclusive to fascia fibroblasts, and requires the upregulation of N-cadherin. Both swarming and N-cadherin expression are absent from fibroblasts in the upper skin layers and the oral mucosa, tissues that repair wounds with minimal scar. Impeding N-cadherin binding inhibits swarming and skin contraction, and leads to reduced scarring in SCADs and in animals. Fibroblast swarming and N-cadherin thus provide therapeutic avenues to curtail fascia mobilisation and pathological fibrotic responses across a range of medical settings.
- Jiang, D.
- Christ, S.
- Correa-Gallegos, D.
- Ramesh, P.
- Kalgudde Gopal, S.
- Wannemacher, J.
- Mayr, C. H.
- Lupperger, V.
- Yu, Q.
- Ye, H.
- Mück-Häusl, M.
- Rajendran, V.
- Wan, L.
- Liu, J.
- Mirastschijski, U.
- Volz, T.
- Marr, C.
- Schiller, H. B.
- Rinkevich, Y.
