---
OA_place: publisher
OA_type: green
_id: '22276'
abstract:
- lang: eng
  text: Tissue tension is a key determinant of tissue shape, and its regulation is
    essential for both morphogenesis and the maintenance of tissue integrity. During
    zebrafish embryogenesis, the enveloping layer (EVL) – an epithelial monolayer
    covering the blastoderm – undergoes extensive spreading that is driven by pulling
    forces exerted at its margin and more than doubles its surface area. Yet whether
    and how the EVL actively regulates its tissue tension during this process remains
    unclear. Here, we show that the EVL maintains constant tissue tension while spreading,
    and that it achieves this by reducing apical cell contractility in response to
    the same pulling forces that drive its spreading. We identify a mechanosensitive
    pathway underlying this response, mediated by the scaffold/adaptor protein Kibra
    regulating the activity of atypical protein kinase C (aPKC) at the apical domain
    of EVL cells. Under low mechanical stretch, Kibra forms condensates at the base
    of actin-based apical projections, where it activates Myosin II to increase apical
    contractility through aPKC downregulation. As mechanical stretch increases, apical
    projections disassemble, Kibra condensates dissolve, and aPKC activity rises.
    Elevated aPKC activity in turn reduces apical contractility by reducing Myosin
    II activity, thereby maintaining constant tissue tension despite increased mechanical
    stretch. Together, these findings reveal a mechanosensitive mechanism that enables
    robust adaptation of tissue tension to changing mechanical stretch, ensuring efficient
    tissue spreading and morphogenesis.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: EM-Fac
acknowledgement: We thank all members of the Heisenberg group for discussion and feedback
  on the manuscript, and the Imaging and Optics Facility, the Life Science Support
  Facility and the Electron Microscopy Facility of the Institute of Science and Technology
  Austria (ISTA) for their continued support. We are grateful to M. Sonawane (Tata
  Institute of Fundamental Research, India) for providing the pCS2-HA-aPKC (PKCι)-V260F
  (DN) and pCS2-HA-aPKC (PKCι)-A122E (CA) plasmids, and to I. Mayer for the discussion.
  Molecular graphics and analyses were performed with UCSF ChimeraX, developed by
  the Resource for Biocomputing, Visualization, and Informatics at the University
  of California, San Francisco, with support from National Institutes of Health R01-GM129325
  and the Office of Cyber Infrastructure and Computational Biology, National Institute
  of Allergy and Infectious Diseases. This research was funded in whole or in part
  by the Austrian Science Fund (FWF; grant no. PAT5044023) to C.-P.H., and by a JSPS
  Overseas Research Fellowship and an EMBO Postdoctoral Fellowship (ALTF 16-2022)
  to N.H.
article_processing_charge: No
author:
- first_name: Naoya
  full_name: Hino, Naoya
  id: 5299a9ce-7679-11eb-a7bc-d1e62b936307
  last_name: Hino
- first_name: Tushna
  full_name: Kapoor, Tushna
  id: e3b3eda7-fd4d-11eb-8fd8-c40af7a478b1
  last_name: Kapoor
- first_name: Uday R
  full_name: Gubbala, Uday R
  id: bb4a0dc4-32c9-11ee-b5ce-a97ceedd5924
  last_name: Gubbala
- first_name: Edouard B
  full_name: Hannezo, Edouard B
  id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
  last_name: Hannezo
  orcid: 0000-0001-6005-1561
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
citation:
  ama: Hino N, Kapoor T, Gubbala UR, Hannezo EB, Heisenberg C-PJ. Apical domain mechanosensation
    regulates tissue tension homeostasis.
  apa: Hino, N., Kapoor, T., Gubbala, U. R., Hannezo, E. B., & Heisenberg, C.-P.
    J. (n.d.). Apical domain mechanosensation regulates tissue tension homeostasis.
    Institute of Science and Technology Austria.
  chicago: Hino, Naoya, Tushna Kapoor, Uday R Gubbala, Edouard B Hannezo, and Carl-Philipp
    J Heisenberg. “Apical Domain Mechanosensation Regulates Tissue Tension Homeostasis.”
    Institute of Science and Technology Austria, n.d.
  ieee: N. Hino, T. Kapoor, U. R. Gubbala, E. B. Hannezo, and C.-P. J. Heisenberg,
    “Apical domain mechanosensation regulates tissue tension homeostasis.” Institute
    of Science and Technology Austria.
  ista: Hino N, Kapoor T, Gubbala UR, Hannezo EB, Heisenberg C-PJ. Apical domain mechanosensation
    regulates tissue tension homeostasis.
  mla: Hino, Naoya, et al. <i>Apical Domain Mechanosensation Regulates Tissue Tension
    Homeostasis</i>. Institute of Science and Technology Austria.
  short: N. Hino, T. Kapoor, U.R. Gubbala, E.B. Hannezo, C.-P.J. Heisenberg, (n.d.).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: "The MATLAB code for image analysis, and the full model
  code, including all parameter values\r\nand condition-specific settings, are available
  on GitHub at https://github.com/uday2607/EVL-tension-homeostasis.git."
date_created: 2026-07-13T09:03:26Z
date_published: 2026-07-14T00:00:00Z
date_updated: 2026-07-14T07:07:41Z
day: '14'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
- _id: GradSch
file:
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  date_updated: 2026-07-13T09:16:20Z
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  date_created: 2026-07-13T09:16:25Z
  date_updated: 2026-07-13T09:16:25Z
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  date_created: 2026-07-13T09:16:28Z
  date_updated: 2026-07-13T09:16:28Z
  file_id: '22285'
  file_name: Supplementary_Video1.mp4
  file_size: 10349451
  relation: main_file
  success: 1
file_date_updated: 2026-07-13T09:16:28Z
has_accepted_license: '1'
keyword:
- Epithelial spreading
- tissue tension
- mechanosensation
- aPKC
- Kibra
- zebrafish
language:
- iso: eng
month: '07'
oa: 1
oa_version: Preprint
project:
- _id: 8f060199-16d5-11f0-9cad-f3253b266c46
  grant_number: PAT 5044023
  name: Keratins in epithelial tissue spreading
- _id: 34dd7f3b-11ca-11ed-8bc3-856f2c87f5da
  grant_number: LTF 16-2022
  name: Mechanosensitive signaling activation in the crosstalk between mechanical
    force and tissuefluidity
publication_status: draft
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '21864'
    relation: earlier_version
    status: public
researchdata_availability: yes
status: public
supplementarymaterial: yes
title: Apical domain mechanosensation regulates tissue tension homeostasis
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20188'
abstract:
- lang: eng
  text: 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.
acknowledgement: We are grateful to the members of the Matsuda Laboratory for their
  helpful input, to K. Hirano, T. Uesugi and K. Takakura, who provided technical assistance,
  and to the Medical Research Support Center of Kyoto University for DNA sequence
  analysis. This work was supported by the Kyoto University Live Imaging Center. Financial
  support was provided by Japan Society for the Promotion of Science (JSPS) KAKENHI
  grants (21H05226 to K.T., 19H00993 and 20H05898 to M.M.), a Japan Science and Technology
  Agency (JST) CREST grant (JPMJCR1654 to M.M.), and a JST Moonshot Research and Development
  Program grant (JPMJPS2022 to M.M.). Open Access funding provided by Tokushima University.
  Deposited in PMC for immediate release.
article_number: '263779'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Yuya
  full_name: Jikko, Yuya
  last_name: Jikko
- first_name: Eriko
  full_name: Deguchi, Eriko
  last_name: Deguchi
- first_name: Kimiya
  full_name: Matsuda, Kimiya
  last_name: Matsuda
- first_name: Naoya
  full_name: Hino, Naoya
  id: 5299a9ce-7679-11eb-a7bc-d1e62b936307
  last_name: Hino
- first_name: Shinya
  full_name: Tsukiji, Shinya
  last_name: Tsukiji
- first_name: Michiyuki
  full_name: Matsuda, Michiyuki
  last_name: Matsuda
- first_name: Kenta
  full_name: Terai, Kenta
  last_name: Terai
citation:
  ama: Jikko Y, Deguchi E, Matsuda K, et al. Front-biased activation of the Ras-Rab5-Rac1
    loop coordinates collective cell migration. <i>Journal of Cell Science</i>. 2025;138(15).
    doi:<a href="https://doi.org/10.1242/jcs.263779">10.1242/jcs.263779</a>
  apa: Jikko, Y., Deguchi, E., Matsuda, K., Hino, N., Tsukiji, S., Matsuda, M., &#38;
    Terai, K. (2025). Front-biased activation of the Ras-Rab5-Rac1 loop coordinates
    collective cell migration. <i>Journal of Cell Science</i>. The Company of Biologists.
    <a href="https://doi.org/10.1242/jcs.263779">https://doi.org/10.1242/jcs.263779</a>
  chicago: Jikko, Yuya, Eriko Deguchi, Kimiya Matsuda, Naoya Hino, Shinya Tsukiji,
    Michiyuki Matsuda, and Kenta Terai. “Front-Biased Activation of the Ras-Rab5-Rac1
    Loop Coordinates Collective Cell Migration.” <i>Journal of Cell Science</i>. The
    Company of Biologists, 2025. <a href="https://doi.org/10.1242/jcs.263779">https://doi.org/10.1242/jcs.263779</a>.
  ieee: Y. Jikko <i>et al.</i>, “Front-biased activation of the Ras-Rab5-Rac1 loop
    coordinates collective cell migration,” <i>Journal of Cell Science</i>, vol. 138,
    no. 15. The Company of Biologists, 2025.
  ista: Jikko Y, Deguchi E, Matsuda K, Hino N, Tsukiji S, Matsuda M, Terai K. 2025.
    Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell
    migration. Journal of Cell Science. 138(15), 263779.
  mla: Jikko, Yuya, et al. “Front-Biased Activation of the Ras-Rab5-Rac1 Loop Coordinates
    Collective Cell Migration.” <i>Journal of Cell Science</i>, vol. 138, no. 15,
    263779, The Company of Biologists, 2025, doi:<a href="https://doi.org/10.1242/jcs.263779">10.1242/jcs.263779</a>.
  short: Y. Jikko, E. Deguchi, K. Matsuda, N. Hino, S. Tsukiji, M. Matsuda, K. Terai,
    Journal of Cell Science 138 (2025).
date_created: 2025-08-17T22:01:36Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2025-11-27T14:12:24Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.1242/jcs.263779
external_id:
  isi:
  - '001567723900009'
  pmid:
  - '40667649'
file:
- access_level: open_access
  checksum: 29f42619dab5ce251a20c769ed4581c0
  content_type: application/pdf
  creator: dernst
  date_created: 2025-09-01T10:02:24Z
  date_updated: 2025-09-01T10:02:24Z
  file_id: '20262'
  file_name: 2025_JourCellScience_Jikko.pdf
  file_size: 12393297
  relation: main_file
  success: 1
file_date_updated: 2025-09-01T10:02:24Z
has_accepted_license: '1'
intvolume: '       138'
isi: 1
issue: '15'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Science
publication_identifier:
  eissn:
  - 1477-9137
  issn:
  - ' 0021-9533'
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell
  migration
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 138
year: '2025'
...
---
OA_type: closed access
_id: '18651'
abstract:
- lang: eng
  text: 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.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Naoya
  full_name: Hino, Naoya
  id: 5299a9ce-7679-11eb-a7bc-d1e62b936307
  last_name: Hino
- first_name: Carolina
  full_name: Santos Fernandes Lasbarrères Camelo, Carolina
  id: 6347dca5-074c-11ed-af92-a80f860d9d5b
  last_name: Santos Fernandes Lasbarrères Camelo
- first_name: Carl-Philipp J
  full_name: Heisenberg, Carl-Philipp J
  id: 39427864-F248-11E8-B48F-1D18A9856A87
  last_name: Heisenberg
  orcid: 0000-0002-0912-4566
citation:
  ama: 'Hino N, Santos Fernandes Lasbarrères Camelo C, Heisenberg C-PJ. Development:
    Turing mechanics. <i>Current Biology</i>. 2024;34(24):R1230-R1232. doi:<a href="https://doi.org/10.1016/j.cub.2024.10.065">10.1016/j.cub.2024.10.065</a>'
  apa: 'Hino, N., Santos Fernandes Lasbarrères Camelo, C., &#38; Heisenberg, C.-P.
    J. (2024). Development: Turing mechanics. <i>Current Biology</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.cub.2024.10.065">https://doi.org/10.1016/j.cub.2024.10.065</a>'
  chicago: 'Hino, Naoya, Carolina Santos Fernandes Lasbarrères Camelo, and Carl-Philipp
    J Heisenberg. “Development: Turing Mechanics.” <i>Current Biology</i>. Elsevier,
    2024. <a href="https://doi.org/10.1016/j.cub.2024.10.065">https://doi.org/10.1016/j.cub.2024.10.065</a>.'
  ieee: 'N. Hino, C. Santos Fernandes Lasbarrères Camelo, and C.-P. J. Heisenberg,
    “Development: Turing mechanics,” <i>Current Biology</i>, vol. 34, no. 24. Elsevier,
    pp. R1230–R1232, 2024.'
  ista: 'Hino N, Santos Fernandes Lasbarrères Camelo C, Heisenberg C-PJ. 2024. Development:
    Turing mechanics. Current Biology. 34(24), R1230–R1232.'
  mla: 'Hino, Naoya, et al. “Development: Turing Mechanics.” <i>Current Biology</i>,
    vol. 34, no. 24, Elsevier, 2024, pp. R1230–32, doi:<a href="https://doi.org/10.1016/j.cub.2024.10.065">10.1016/j.cub.2024.10.065</a>.'
  short: N. Hino, C. Santos Fernandes Lasbarrères Camelo, C.-P.J. Heisenberg, Current
    Biology 34 (2024) R1230–R1232.
corr_author: '1'
date_created: 2024-12-15T23:01:49Z
date_published: 2024-12-16T00:00:00Z
date_updated: 2025-09-09T11:51:15Z
day: '16'
department:
- _id: CaHe
doi: 10.1016/j.cub.2024.10.065
external_id:
  isi:
  - '001392077000001'
  pmid:
  - '39689690'
intvolume: '        34'
isi: 1
issue: '24'
language:
- iso: eng
month: '12'
oa_version: None
page: R1230-R1232
pmid: 1
publication: Current Biology
publication_identifier:
  eissn:
  - 1879-0445
  issn:
  - 0960-9822
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Development: Turing mechanics'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 34
year: '2024'
...
---
_id: '14080'
abstract:
- lang: eng
  text: 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.
acknowledgement: TH was supported by JSPS KAKENHI Grant (no. 21H05290) and the Ministry
  of Education under the Research Centres of Excellence programme through the Mechanobiology
  Institute at National University of Singapore and by Department of Physiology at
  National University of Singapore. NH was supported by JSPS KAKENHI Grant (no. 20K22653).
  KA was supported by JSPS KAKENHI Grants (no. 19H05798 and no. 22H02625). MM was
  supported by JSPS KAKENHI Grants (no. 19H00993 and no. 20H05898) and JST Moonshot
  R&D Grant JPMJPS2022. We appreciate Virgile Viasnoff and the lab members for their
  valuable comments on the manuscript. We apologize to authors whose work could not
  be highlighted due to space limitations.
article_number: '102217'
article_processing_charge: Yes (in subscription journal)
article_type: review
author:
- first_name: Tsuyoshi
  full_name: Hirashima, Tsuyoshi
  last_name: Hirashima
- first_name: Naoya
  full_name: Hino, Naoya
  id: 5299a9ce-7679-11eb-a7bc-d1e62b936307
  last_name: Hino
- first_name: Kazuhiro
  full_name: Aoki, Kazuhiro
  last_name: Aoki
- first_name: Michiyuki
  full_name: Matsuda, Michiyuki
  last_name: Matsuda
citation:
  ama: Hirashima T, Hino N, Aoki K, Matsuda M. Stretching the limits of extracellular
    signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation.
    <i>Current Opinion in Cell Biology</i>. 2023;84(10). doi:<a href="https://doi.org/10.1016/j.ceb.2023.102217">10.1016/j.ceb.2023.102217</a>
  apa: Hirashima, T., Hino, N., Aoki, K., &#38; Matsuda, M. (2023). Stretching the
    limits of extracellular signal-related kinase (ERK) signaling — Cell mechanosensing
    to ERK activation. <i>Current Opinion in Cell Biology</i>. Elsevier. <a href="https://doi.org/10.1016/j.ceb.2023.102217">https://doi.org/10.1016/j.ceb.2023.102217</a>
  chicago: Hirashima, Tsuyoshi, Naoya Hino, Kazuhiro Aoki, and Michiyuki Matsuda.
    “Stretching the Limits of Extracellular Signal-Related Kinase (ERK) Signaling
    — Cell Mechanosensing to ERK Activation.” <i>Current Opinion in Cell Biology</i>.
    Elsevier, 2023. <a href="https://doi.org/10.1016/j.ceb.2023.102217">https://doi.org/10.1016/j.ceb.2023.102217</a>.
  ieee: T. Hirashima, N. Hino, K. Aoki, and M. Matsuda, “Stretching the limits of
    extracellular signal-related kinase (ERK) signaling — Cell mechanosensing to ERK
    activation,” <i>Current Opinion in Cell Biology</i>, vol. 84, no. 10. Elsevier,
    2023.
  ista: Hirashima T, Hino N, Aoki K, Matsuda M. 2023. Stretching the limits of extracellular
    signal-related kinase (ERK) signaling — Cell mechanosensing to ERK activation.
    Current Opinion in Cell Biology. 84(10), 102217.
  mla: Hirashima, Tsuyoshi, et al. “Stretching the Limits of Extracellular Signal-Related
    Kinase (ERK) Signaling — Cell Mechanosensing to ERK Activation.” <i>Current Opinion
    in Cell Biology</i>, vol. 84, no. 10, 102217, Elsevier, 2023, doi:<a href="https://doi.org/10.1016/j.ceb.2023.102217">10.1016/j.ceb.2023.102217</a>.
  short: T. Hirashima, N. Hino, K. Aoki, M. Matsuda, Current Opinion in Cell Biology
    84 (2023).
date_created: 2023-08-20T22:01:12Z
date_published: 2023-10-01T00:00:00Z
date_updated: 2024-01-30T12:52:42Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.1016/j.ceb.2023.102217
external_id:
  isi:
  - '001054692200001'
  pmid:
  - '37574635'
file:
- access_level: open_access
  checksum: 25923f8ae71344e8974530dd23c71bdc
  content_type: application/pdf
  creator: dernst
  date_created: 2024-01-30T12:52:12Z
  date_updated: 2024-01-30T12:52:12Z
  file_id: '14909'
  file_name: 2023_CurrentOpinionCellBio_Hirashima.pdf
  file_size: 1173762
  relation: main_file
  success: 1
file_date_updated: 2024-01-30T12:52:12Z
has_accepted_license: '1'
intvolume: '        84'
isi: 1
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
pmid: 1
publication: Current Opinion in Cell Biology
publication_identifier:
  eissn:
  - 1879-0410
  issn:
  - 0955-0674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Stretching the limits of extracellular signal-related kinase (ERK) signaling
  — Cell mechanosensing to ERK activation
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 84
year: '2023'
...
---
OA_place: publisher
OA_type: free access
_id: '12238'
abstract:
- lang: eng
  text: 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.
acknowledgement: We thank the members of the Matsuda Laboratory for their helpful
  discussion and encouragement, and we thank K. Hirano and K. Takakura for their technical
  assistance. This work was supported by the Kyoto University Live Imaging Center.
  Financial support was provided in the form of JSPS KAKENHI grants (nos. 17J02107
  and 20K22653 to N.H., and 20H05898 and 19H00993 to M.M.), a JST CREST grant (no.
  JPMJCR1654 to M.M.), a Moonshot R&D grant (no. JPMJPS2022-11 to M.M.), Generalitat
  de Catalunya and the CERCA Programme (no. SGR-2017-01602 to X.T.), MICCINN/FEDER
  (no. PGC2018-099645-B-I00 to X.T.), and European Research Council (no. Adv-883739
  to X.T.). IBEC is a recipient of a Severo Ochoa Award of Excellence from the MINECO.
  This work was partly supported by an Extramural Collaborative Research Grant of
  Cancer Research Institute, Kanazawa University.
article_processing_charge: No
article_type: original
author:
- first_name: Naoya
  full_name: Hino, Naoya
  id: 5299a9ce-7679-11eb-a7bc-d1e62b936307
  last_name: Hino
- first_name: Kimiya
  full_name: Matsuda, Kimiya
  last_name: Matsuda
- first_name: Yuya
  full_name: Jikko, Yuya
  last_name: Jikko
- first_name: Gembu
  full_name: Maryu, Gembu
  last_name: Maryu
- first_name: Katsuya
  full_name: Sakai, Katsuya
  last_name: Sakai
- first_name: Ryu
  full_name: Imamura, Ryu
  last_name: Imamura
- first_name: Shinya
  full_name: Tsukiji, Shinya
  last_name: Tsukiji
- first_name: Kazuhiro
  full_name: Aoki, Kazuhiro
  last_name: Aoki
- first_name: Kenta
  full_name: Terai, Kenta
  last_name: Terai
- first_name: Tsuyoshi
  full_name: Hirashima, Tsuyoshi
  last_name: Hirashima
- first_name: Xavier
  full_name: Trepat, Xavier
  last_name: Trepat
- first_name: Michiyuki
  full_name: Matsuda, Michiyuki
  last_name: Matsuda
citation:
  ama: Hino N, Matsuda K, Jikko Y, et al. A feedback loop between lamellipodial extension
    and HGF-ERK signaling specifies leader cells during collective cell migration.
    <i>Developmental Cell</i>. 2022;57(19):2290-2304.e7. doi:<a href="https://doi.org/10.1016/j.devcel.2022.09.003">10.1016/j.devcel.2022.09.003</a>
  apa: Hino, N., Matsuda, K., Jikko, Y., Maryu, G., Sakai, K., Imamura, R., … Matsuda,
    M. (2022). A feedback loop between lamellipodial extension and HGF-ERK signaling
    specifies leader cells during collective cell migration. <i>Developmental Cell</i>.
    Elsevier. <a href="https://doi.org/10.1016/j.devcel.2022.09.003">https://doi.org/10.1016/j.devcel.2022.09.003</a>
  chicago: Hino, Naoya, Kimiya Matsuda, Yuya Jikko, Gembu Maryu, Katsuya Sakai, Ryu
    Imamura, Shinya Tsukiji, et al. “A Feedback Loop between Lamellipodial Extension
    and HGF-ERK Signaling Specifies Leader Cells during Collective Cell Migration.”
    <i>Developmental Cell</i>. Elsevier, 2022. <a href="https://doi.org/10.1016/j.devcel.2022.09.003">https://doi.org/10.1016/j.devcel.2022.09.003</a>.
  ieee: N. Hino <i>et al.</i>, “A feedback loop between lamellipodial extension and
    HGF-ERK signaling specifies leader cells during collective cell migration,” <i>Developmental
    Cell</i>, vol. 57, no. 19. Elsevier, p. 2290–2304.e7, 2022.
  ista: Hino N, Matsuda K, Jikko Y, Maryu G, Sakai K, Imamura R, Tsukiji S, Aoki K,
    Terai K, Hirashima T, Trepat X, Matsuda M. 2022. A feedback loop between lamellipodial
    extension and HGF-ERK signaling specifies leader cells during collective cell
    migration. Developmental Cell. 57(19), 2290–2304.e7.
  mla: Hino, Naoya, et al. “A Feedback Loop between Lamellipodial Extension and HGF-ERK
    Signaling Specifies Leader Cells during Collective Cell Migration.” <i>Developmental
    Cell</i>, vol. 57, no. 19, Elsevier, 2022, p. 2290–2304.e7, doi:<a href="https://doi.org/10.1016/j.devcel.2022.09.003">10.1016/j.devcel.2022.09.003</a>.
  short: N. Hino, K. Matsuda, Y. Jikko, G. Maryu, K. Sakai, R. Imamura, S. Tsukiji,
    K. Aoki, K. Terai, T. Hirashima, X. Trepat, M. Matsuda, Developmental Cell 57
    (2022) 2290–2304.e7.
corr_author: '1'
date_created: 2023-01-16T09:51:39Z
date_published: 2022-10-01T00:00:00Z
date_updated: 2026-06-18T17:25:21Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.1016/j.devcel.2022.09.003
external_id:
  isi:
  - '000898428700006'
  pmid:
  - '36174555'
intvolume: '        57'
isi: 1
issue: '19'
keyword:
- Developmental Biology
- Cell Biology
- General Biochemistry
- Genetics and Molecular Biology
- Molecular Biology
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1016/j.devcel.2022.09.003
month: '10'
oa: 1
oa_version: Published Version
page: 2290-2304.e7
pmid: 1
publication: Developmental Cell
publication_identifier:
  issn:
  - 1534-5807
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: A feedback loop between lamellipodial extension and HGF-ERK signaling specifies
  leader cells during collective cell migration
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 57
year: '2022'
...