1. Developmental Biology
  2. Physics of Living Systems
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Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Research Article
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Cite this article as: eLife 2020;9:e58945 doi: 10.7554/eLife.58945

Abstract

The coordination of cell proliferation and migration in growing tissues is crucial in development and regeneration but remains poorly understood. Here, we find that, while expanding with an edge speed independent of initial conditions, millimeter-scale epithelial monolayers exhibit internal patterns of proliferation and migration that depend not on the current but on the initial tissue size, indicating memory effects. Specifically, the core of large tissues becomes very dense, almost quiescent, and ceases cell-cycle progression. In contrast, initially-smaller tissues develop a local minimum of cell density and a tissue-spanning vortex. To explain vortex formation, we propose an active polar fluid model with a feedback between cell polarization and tissue flow. Taken together, our findings suggest that expanding epithelia decouple their internal and edge regions, which enables robust expansion dynamics despite the presence of size and history-dependent patterns in the tissue interior.

Data availability

Representative raw datasets for each Figure are available at Zenodo DOI: 10.5281/zenodo.3858845Full raw dataset is hundreds of gigabytes due to the video data and can be provided upon request. Key analysis code provided at our github repository: Github DOI: 10.5281/zenodo.3861843

Article and author information

Author details

  1. Matthew A Heinrich

    Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ricard Alert

    Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1885-9177
  3. Julienne M LaChance

    Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tom J Zajdel

    Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrej Košmrlj

    Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6137-9200
  6. Daniel J Cohen

    Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, United States
    For correspondence
    danielcohen@princeton.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5819-1135

Funding

National Institutes of Health (1 R35GM133574-01)

  • Daniel J Cohen

Human Frontiers of Science Program (LT000475/2018-C)

  • Ricard Alert

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jody Rosenblatt, King's College London, United Kingdom

Publication history

  1. Received: May 15, 2020
  2. Accepted: August 18, 2020
  3. Accepted Manuscript published: August 19, 2020 (version 1)
  4. Version of Record published: September 17, 2020 (version 2)

Copyright

© 2020, Heinrich et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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