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

Version 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.

Metrics

  • 5,323
    Page views
  • 701
    Downloads
  • 25
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Matthew A Heinrich
  2. Ricard Alert
  3. Julienne M LaChance
  4. Tom J Zajdel
  5. Andrej Košmrlj
  6. Daniel J Cohen
(2020)
Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia
eLife 9:e58945.
https://doi.org/10.7554/eLife.58945

Share this article

https://doi.org/10.7554/eLife.58945

Further reading

    1. Developmental Biology
    Chhavi Sood, Md Ausrafuggaman Nahid ... Sarah E Siegrist
    Research Article

    Neuroblasts in Drosophila divide asymmetrically, sequentially expressing a series of intrinsic factors to generate a diversity of neuron types. These intrinsic factors known as temporal factors dictate timing of neuroblast transitions in response to steroid hormone signaling and specify early versus late temporal fates in neuroblast neuron progeny. After completing their temporal programs, neuroblasts differentiate or die, finalizing both neuron number and type within each neuroblast lineage. From a screen aimed at identifying genes required to terminate neuroblast divisions, we identified Notch and Notch pathway components. When Notch is knocked down, neuroblasts maintain early temporal factor expression longer, delay late temporal factor expression, and continue dividing into adulthood. We find that Delta, expressed in cortex glia, neuroblasts, and after division, their GMC progeny, regulates neuroblast Notch activity. We also find that Delta in neuroblasts is expressed high early, low late, and is controlled by the intrinsic temporal program: early factor Imp promotes Delta, late factors Syp/E93 reduce Delta. Thus, in addition to systemic steroid hormone cues, forward lineage progression is controlled by local cell-cell signaling between neuroblasts and their cortex glia/GMC neighbors: Delta transactivates Notch in neuroblasts bringing the early temporal program and early temporal factor expression to a close.

    1. Developmental Biology
    Nicolas G Brukman, Clari Valansi, Benjamin Podbilewicz
    Research Article Updated

    The fusion of mammalian gametes requires the interaction between IZUMO1 on the sperm and JUNO on the oocyte. We have recently shown that ectopic expression of mouse IZUMO1 induces cell-cell fusion and that sperm can fuse to fibroblasts expressing JUNO. Here, we found that the incubation of mouse sperm with hamster fibroblasts or human epithelial cells in culture induces the fusion between these somatic cells and the formation of syncytia, a pattern previously observed with some animal viruses. This sperm-induced cell-cell fusion requires a species-matching JUNO on both fusing cells, can be blocked by an antibody against IZUMO1, and does not rely on the synthesis of new proteins. The fusion is dependent on the sperm’s fusogenic capacity, making this a reliable, fast, and simple method for predicting sperm function during the diagnosis of male infertility.