---
_id: '12209'
abstract:
- lang: eng
  text: Embryo development requires biochemical signalling to generate patterns of
    cell fates and active mechanical forces to drive tissue shape changes. However,
    how these processes are coordinated, and how tissue patterning is preserved despite
    the cellular flows occurring during morphogenesis, remains poorly understood.
    Gastrulation is a crucial embryonic stage that involves both patterning and internalization
    of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos,
    a gradient in Nodal signalling orchestrates pattern-preserving internalization
    movements by triggering a motility-driven unjamming transition. In addition to
    its role as a morphogen determining embryo patterning, graded Nodal signalling
    mechanically subdivides the mesendoderm into a small fraction of highly protrusive
    leader cells, able to autonomously internalize via local unjamming, and less protrusive
    followers, which need to be pulled inwards by the leaders. The Nodal gradient
    further enforces a code of preferential adhesion coupling leaders to their immediate
    followers, resulting in a collective and ordered mode of internalization that
    preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal
    signalling into minimal active particle simulations quantitatively predicts both
    physiological and experimentally perturbed internalization movements. This provides
    a quantitative framework for how a morphogen-encoded unjamming transition can
    bidirectionally couple tissue mechanics with patterning during complex three-dimensional
    morphogenesis.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: "We thank K. Sampath, A. Pauli and Y. Bellaїche for feedback on the
  manuscript. We also thank the members of the Heisenberg group, in particular A.
  Schauer and F. Nur Arslan, for help, technical advice and discussions, and the Bioimaging
  and Life Science facilities at IST\r\nAustria for continuous support. We thank C.
  Flandoli for the artwork in the figures. This work was supported by postdoctoral
  fellowships from EMBO (LTF-850-2017) and HFSP (LT000429/2018-L2) to D.P. and the
  European Union (European Research Council starting grant 851288 to É.H. and European
  Research Council advanced grant 742573 to C.-P.H.)."
article_processing_charge: No
article_type: original
author:
- first_name: Diana C
  full_name: Nunes Pinheiro, Diana C
  id: 2E839F16-F248-11E8-B48F-1D18A9856A87
  last_name: Nunes Pinheiro
  orcid: 0000-0003-4333-7503
- first_name: Roland
  full_name: Kardos, Roland
  id: 4039350E-F248-11E8-B48F-1D18A9856A87
  last_name: Kardos
- 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: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. Morphogen gradient
    orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming.
    <i>Nature Physics</i>. 2022;18(12):1482-1493. doi:<a href="https://doi.org/10.1038/s41567-022-01787-6">10.1038/s41567-022-01787-6</a>
  apa: Nunes Pinheiro, D. C., Kardos, R., Hannezo, E. B., &#38; Heisenberg, C.-P.
    J. (2022). Morphogen gradient orchestrates pattern-preserving tissue morphogenesis
    via motility-driven unjamming. <i>Nature Physics</i>. Springer Nature. <a href="https://doi.org/10.1038/s41567-022-01787-6">https://doi.org/10.1038/s41567-022-01787-6</a>
  chicago: Nunes Pinheiro, Diana C, Roland Kardos, Edouard B Hannezo, and Carl-Philipp
    J Heisenberg. “Morphogen Gradient Orchestrates Pattern-Preserving Tissue Morphogenesis
    via Motility-Driven Unjamming.” <i>Nature Physics</i>. Springer Nature, 2022.
    <a href="https://doi.org/10.1038/s41567-022-01787-6">https://doi.org/10.1038/s41567-022-01787-6</a>.
  ieee: D. C. Nunes Pinheiro, R. Kardos, E. B. Hannezo, and C.-P. J. Heisenberg, “Morphogen
    gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven
    unjamming,” <i>Nature Physics</i>, vol. 18, no. 12. Springer Nature, pp. 1482–1493,
    2022.
  ista: Nunes Pinheiro DC, Kardos R, Hannezo EB, Heisenberg C-PJ. 2022. Morphogen
    gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven
    unjamming. Nature Physics. 18(12), 1482–1493.
  mla: Nunes Pinheiro, Diana C., et al. “Morphogen Gradient Orchestrates Pattern-Preserving
    Tissue Morphogenesis via Motility-Driven Unjamming.” <i>Nature Physics</i>, vol.
    18, no. 12, Springer Nature, 2022, pp. 1482–93, doi:<a href="https://doi.org/10.1038/s41567-022-01787-6">10.1038/s41567-022-01787-6</a>.
  short: D.C. Nunes Pinheiro, R. Kardos, E.B. Hannezo, C.-P.J. Heisenberg, Nature
    Physics 18 (2022) 1482–1493.
corr_author: '1'
date_created: 2023-01-16T09:45:19Z
date_published: 2022-12-01T00:00:00Z
date_updated: 2025-04-14T07:46:59Z
day: '01'
ddc:
- '570'
department:
- _id: CaHe
- _id: EdHa
doi: 10.1038/s41567-022-01787-6
ec_funded: 1
external_id:
  isi:
  - '000871319900002'
file:
- access_level: open_access
  checksum: c86a8e8d80d1bfc46d56a01e88a2526a
  content_type: application/pdf
  creator: dernst
  date_created: 2023-01-27T07:32:01Z
  date_updated: 2023-01-27T07:32:01Z
  file_id: '12412'
  file_name: 2022_NaturePhysics_Pinheiro.pdf
  file_size: 36703569
  relation: main_file
  success: 1
file_date_updated: 2023-01-27T07:32:01Z
has_accepted_license: '1'
intvolume: '        18'
isi: 1
issue: '12'
keyword:
- General Physics and Astronomy
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 1482-1493
project:
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 850-2017
  name: Coordination of mesendoderm cell fate specification and internalization during
    zebrafish gastrulation
- _id: 26520D1E-B435-11E9-9278-68D0E5697425
  grant_number: ALTF 850-2017
  name: Coordination of mesendoderm cell fate specification and internalization during
    zebrafish gastrulation
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
  call_identifier: H2020
  grant_number: '851288'
  name: Design Principles of Branching Morphogenesis
- _id: 260F1432-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '742573'
  name: Interaction and feedback between cell mechanics and fate specification in
    vertebrate gastrulation
publication: Nature Physics
publication_identifier:
  eissn:
  - 1745-2481
  issn:
  - 1745-2473
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via
  motility-driven unjamming
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 18
year: '2022'
...