title: FGF receptors 1 and 2 are key regulators of keratinocyte migration in vitro and in wounded skin.
abstract: Efficient wound repair is essential for the maintenance of the integrity of the skin. The repair process is controlled by a variety of growth factors and cytokines, and their abnormal expression or activity can cause healing disorders. Here, we show that wound repair is severely delayed in mice lacking fibroblast growth factor receptors (FGFR) 1 and 2 in keratinocytes. As the underlying mechanism, we identified impaired wound contraction and a delay in re-epithelialization that resulted from impaired keratinocyte migration at the wound edge. Scratch wounding and transwell assays demonstrated that FGFR1/2-deficient keratinocytes had a reduced migration velocity and impaired directional persistence owing to inefficient formation and turnover of focal adhesions. Underlying this defect, we identified a significant reduction in the expression of major focal adhesion components in the absence of FGFR signaling, resulting in a general migratory deficiency. These results identify FGFs as key regulators of keratinocyte migration in wounded skin.
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, ETH Zurich,  8093 Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Müller
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Yang
authors.forename: Daniel
authors.initials: D
authors.lastname: Moik
authors.forename: Gilles
authors.initials: G
authors.lastname: Ponzio
authors.forename: David M
authors.initials: DM
authors.lastname: Ornitz
authors.forename: Richard
authors.initials: R
authors.lastname: Grose
authors.forename: Sabine
authors.initials: S
authors.lastname: Werner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2