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Dev Cell. 2017 Nov 6;43(3):305-317.e5. doi: 10.1016/j.devcel.2017.10.016.

Propagating Wave of ERK Activation Orients Collective Cell Migration.

Author information

1
Imaging Platform for Spatio-Temporal Information, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Division of Quantitative Biology, Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, Myodaiji, Higashiyama 5-1, Okazaki, Aichi 444-8787, Japan; Department of Basic Biology, Faculty of Life Science, Sokendai (Graduate University for Advanced Studies), Myodaiji, Okazaki, Aichi 444-8787, Japan. Electronic address: k-aoki@nibb.ac.jp.
2
Imaging Platform for Spatio-Temporal Information, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Division of Quantitative Biology, Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, Myodaiji, Higashiyama 5-1, Okazaki, Aichi 444-8787, Japan; Department of Basic Biology, Faculty of Life Science, Sokendai (Graduate University for Advanced Studies), Myodaiji, Okazaki, Aichi 444-8787, Japan; Integrated Systems Biology Laboratory, Graduate School of Informatics, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
3
Imaging Platform for Spatio-Temporal Information, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Integrated Systems Biology Laboratory, Graduate School of Informatics, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
4
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
5
Division of Quantitative Biology, Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, Myodaiji, Higashiyama 5-1, Okazaki, Aichi 444-8787, Japan.
6
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan; Laboratory of Bioimaging and Cell Signaling, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.

Abstract

The biophysical framework of collective cell migration has been extensively investigated in recent years; however, it remains elusive how chemical inputs from neighboring cells are integrated to coordinate the collective movement. Here, we provide evidence that propagation waves of extracellular signal-related kinase (ERK) mitogen-activated protein kinase activation determine the direction of the collective cell migration. A wound-healing assay of Mardin-Darby canine kidney (MDCK) epithelial cells revealed two distinct types of ERK activation wave, a "tidal wave" from the wound, and a self-organized "spontaneous wave" in regions distant from the wound. In both cases, MDCK cells collectively migrated against the direction of the ERK activation wave. The inhibition of ERK activation propagation suppressed collective cell migration. An ERK activation wave spatiotemporally controlled actomyosin contraction and cell density. Furthermore, an optogenetic ERK activation wave reproduced the collective cell migration. These data provide new mechanistic insight into how cells sense the direction of collective cell migration.

KEYWORDS:

ERK; FRET; collective cell migration; force; mathematical model; myosin light chain; simulation

PMID:
29112851
DOI:
10.1016/j.devcel.2017.10.016
[Indexed for MEDLINE]
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