title: Intercellular propagation of extracellular signal-regulated kinase activation revealed by in vivo imaging of mouse skin.
abstract: Extracellular signal-regulated kinase (ERK) is a key effector of many growth signalling pathways. In this study, we visualise epidermal ERK activity in living mice using an ERK FRET biosensor. Under steady-state conditions, the epidermis occasionally revealed bursts of ERK activation patterns where ERK activity radially propagated from cell to cell. The frequency of this spatial propagation of radial ERK activity distribution (SPREAD) correlated with the rate of epidermal cell division. SPREADs and proliferation were stimulated by 12-O-tetradecanoylphorbol 13-acetate (TPA) in a manner dependent on EGF receptors and their cognate ligands. At the wounded skin, ERK activation propagated as trigger wave in parallel to the wound edge, suggesting that ERK activation propagation can be superimposed. Furthermore, by visualising the cell cycle, we found that SPREADs were associated with G2/M cell cycle progression. Our results provide new insights into how cell proliferation and transient ERK activity are synchronised in a living tissue.
authors: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Toru
authors: T
authors: Hiratsuka
authors: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Yoshihisa
authors: Y
authors: Fujita
authors: Imaging Platform for Spatio-Temporal Information, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Honda
authors: H
authors: Naoki
authors: Imaging Platform for Spatio-Temporal Information, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Kazuhiro
authors: K
authors: Aoki
authors: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Yuji
authors: Y
authors: Kamioka
authors: Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors: Michiyuki
authors: M
authors: Matsuda
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004423:Ear; D004789:Enzyme Activation / Q000187:drug effects; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D008822:Mice, Transgenic; D059010:Single-Cell Analysis; D012867:Skin / Q000201:enzymology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate
keywords: ERK; cell biology; cell cycle; epidermis; in vivo imaging; mouse