Propagating Wave of ERK Activation Orients Collective Cell Migration

被引：201

作者：

Aoki, Kazuhiro ^{[1
,2
,3
]}

Kondo, Yohei ^{[1
,2
,3
,4
]}

Naoki, Honda ^{[1
,4
]}

Hiratsuka, Toru ^{[5
]}

Itoh, Reina E. ^{[2
]}

Matsuda, Michiyuki ^{[5
,6
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Imaging Platform Spatiotemporal Informat, Sakyo Ku, Kyoto 6068501, Japan

[2] Natl Inst Nat Sci, Natl Inst Basic Biol, Okazaki Inst Integrat Biosci, Div Quantitat Biol, Higashiyama 5-1, Okazaki, Aichi 4448787, Japan

[3] Sokendai Grad Univ Adv Studies, Fac Life Sci, Dept Basic Biol, Okazaki, Aichi 4448787, Japan

[4] Kyoto Univ, Grad Sch Informat, Integrated Syst Biol Lab, Sakyo Ku, Kyoto 6068501, Japan

[5] Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Sakyo Ku, Kyoto 6068501, Japan

[6] Kyoto Univ, Grad Sch Biostudies, Lab Bioimaging & Cell Signaling, Sakyo Ku, Kyoto 6068501, Japan

来源：

DEVELOPMENTAL CELL | 2017年 / 43卷 / 03期

关键词：

EPITHELIAL-CELLS; FRET BIOSENSORS; MAP KINASE; FORCES; MORPHOGENESIS; GUIDANCE; SUBSTRATE; GRADIENT; DYNAMICS; CASCADE;

D O I：

10.1016/j.devcel.2017.10.016

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：305 / +

页数：18

共 57 条

[1] Refractory nature of normal human diploid fibroblasts with respect to oncogene-mediated transformation [J].