@article{20188,
  abstract     = {Collective cell migration is coordinated by the front-to-rear intercellular propagation of EGFR-Ras-ERK pathway activation. However, the molecular mechanisms integrating front-to-rear information into this intercellular signaling cascade, particularly the determinants of cellular front-side specification, remain elusive. We visualized the activity of EGFR, Ras, Rac1 and Rab5A (hereafter Rab5) by using FRET biosensors and chemogenetic tools. Whereas EGFR activation was uniformly observed within cells, Ras activation was biased to the front side within cells. The polarized Ras activation depended on Merlin and Rac1, which also showed front-biased activation. Furthermore, Rab5, a crucial regulator of cell migration, demonstrated similar front-biased activation and was found to function downstream of Ras while being necessary for Rac1 activation. Thus, the positive feedback loop consisting of Ras, Rab5 and Rac1 is activated primarily at the front of collectively migrating cells. These findings offer new spatio-temporal insight into processing front–rear information during collective cell migration.},
  author       = {Jikko, Yuya and Deguchi, Eriko and Matsuda, Kimiya and Hino, Naoya and Tsukiji, Shinya and Matsuda, Michiyuki and Terai, Kenta},
  issn         = {1477-9137},
  journal      = {Journal of Cell Science},
  number       = {15},
  publisher    = {The Company of Biologists},
  title        = {{Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration}},
  doi          = {10.1242/jcs.263779},
  volume       = {138},
  year         = {2025},
}

@article{18651,
  abstract     = {Embryo axis formation begins with the localized expression of biochemical signals, which organize cell movements and determine cell fate. A quail study finds that tissue contraction and resulting long-range changes in tissue tension restrict the area where these biochemical signals are expressed.},
  author       = {Hino, Naoya and Santos Fernandes Lasbarrères Camelo, Carolina and Heisenberg, Carl-Philipp J},
  issn         = {1879-0445},
  journal      = {Current Biology},
  number       = {24},
  pages        = {R1230--R1232},
  publisher    = {Elsevier},
  title        = {{Development: Turing mechanics}},
  doi          = {10.1016/j.cub.2024.10.065},
  volume       = {34},
  year         = {2024},
}

@article{14080,
  abstract     = {Extracellular signal-regulated kinase (ERK) has been recognized as a critical regulator in various physiological and pathological processes. Extensive research has elucidated the signaling mechanisms governing ERK activation via biochemical regulations with upstream molecules, particularly receptor tyrosine kinases (RTKs). However, recent advances have highlighted the role of mechanical forces in activating the RTK–ERK signaling pathways, thereby opening new avenues of research into mechanochemical interplay in multicellular tissues. Here, we review the force-induced ERK activation in cells and propose possible mechanosensing mechanisms underlying the mechanoresponsive ERK activation. We conclude that mechanical forces are not merely passive factors shaping cells and tissues but also active regulators of cellular signaling pathways controlling collective cell behaviors.},
  author       = {Hirashima, Tsuyoshi and Hino, Naoya and Aoki, Kazuhiro and Matsuda, Michiyuki},
  issn         = {1879-0410},
  journal      = {Current Opinion in Cell Biology},
  number       = {10},
  publisher    = {Elsevier},
  title        = {{Stretching the limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation}},
  doi          = {10.1016/j.ceb.2023.102217},
  volume       = {84},
  year         = {2023},
}

@article{12238,
  abstract     = {Upon the initiation of collective cell migration, the cells at the free edge are specified as leader cells; however, the mechanism underlying the leader cell specification remains elusive. Here, we show that lamellipodial extension after the release from mechanical confinement causes sustained extracellular signal-regulated kinase (ERK) activation and underlies the leader cell specification. Live-imaging of Madin-Darby canine kidney (MDCK) cells and mouse epidermis through the use of Förster resonance energy transfer (FRET)-based biosensors showed that leader cells exhibit sustained ERK activation in a hepatocyte growth factor (HGF)-dependent manner. Meanwhile, follower cells exhibit oscillatory ERK activation waves in an epidermal growth factor (EGF) signaling-dependent manner. Lamellipodial extension at the free edge increases the cellular sensitivity to HGF. The HGF-dependent ERK activation, in turn, promotes lamellipodial extension, thereby forming a positive feedback loop between cell extension and ERK activation and specifying the cells at the free edge as the leader cells. Our findings show that the integration of physical and biochemical cues underlies the leader cell specification during collective cell migration.},
  author       = {Hino, Naoya and Matsuda, Kimiya and Jikko, Yuya and Maryu, Gembu and Sakai, Katsuya and Imamura, Ryu and Tsukiji, Shinya and Aoki, Kazuhiro and Terai, Kenta and Hirashima, Tsuyoshi and Trepat, Xavier and Matsuda, Michiyuki},
  issn         = {1534-5807},
  journal      = {Developmental Cell},
  keywords     = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology},
  number       = {19},
  pages        = {2290--2304.e7},
  publisher    = {Elsevier},
  title        = {{A feedback loop between lamellipodial extension and HGF-ERK signaling specifies leader cells during collective cell migration}},
  doi          = {10.1016/j.devcel.2022.09.003},
  volume       = {57},
  year         = {2022},
}