Propagating Wave of ERK Activation Orients Collective Cell Migration

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 sig...

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Bibliographic Details
Published in:Developmental cell Vol. 43; no. 3; p. 305
Main Authors: Aoki, Kazuhiro, Kondo, Yohei, Naoki, Honda, Hiratsuka, Toru, Itoh, Reina E, Matsuda, Michiyuki
Format: Journal Article
Language:English
Published: United States 06.11.2017
Subjects:
Actomyosin - metabolism
Animals
Cell Movement - physiology
Dogs
Enzyme Activation
Epithelial Cells - cytology
Kidney - metabolism
MAP Kinase Signaling System - physiology
Mitogen-Activated Protein Kinases - metabolism
Phosphorylation
Wound Healing - physiology
myosin light chain
simulation
mathematical model
FRET
force
collective cell migration
ERK
ISSN:1878-1551, 1878-1551
Online Access:Get more information
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Summary: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.
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ISSN:1878-1551
1878-1551
DOI:10.1016/j.devcel.2017.10.016