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3D Cell neighbour dynamics in growing pseudostratified epithelia

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Cite this article as: eLife 2021;10:e68135 doi: 10.7554/eLife.68135


During morphogenesis, epithelial sheets remodel into complex geometries. How cells dynamically organize their contact with neighbouring cells in these tightly packed tissues is poorly understood. We have used light-sheet microscopy of growing mouse embryonic lung explants, three-dimensional cell segmentation, and physical theory to unravel the principles behind 3D cell organization in growing pseudostratified epithelia. We find that cells have highly irregular 3D shapes and exhibit numerous neighbour intercalations along the apical-basal axis as well as over time. Despite the fluidic nature, the cell packing configurations follow fundamental relationships previously described for apical epithelial layers, i.e., Euler's formula, Lewis' law, and Aboav-Weaire's law, at all times and across the entire tissue thickness. This arrangement minimizes the lateral cell-cell surface energy for a given cross-sectional area variability, generated primarily by the distribution and movement of nuclei. We conclude that the complex 3D cell organization in growing epithelia emerges from simple physical principles.

Data availability

The source code and plotted data files are available as a git repository at https://git.bsse.ethz.ch/iber/Publications/2021_gomez_3d_cell_neighbour_dynamics.git. The raw data is publicly available as openBIS repository at https://openbis-data-repo.ethz.ch/openbis/webapp/eln-lims/?user=observer&pass=openbis under the Name 3D Epithelium.

The following data sets were generated

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Author details

  1. Harold Fernando Gomez

    D-BSSE, ETH Zurich, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Mathilde Sabine Dumond

    D-BSSE, ETH Zurich, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Leonie Hodel

    D-BSSE, ETH Zurich, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Roman Vetter

    D-BSSE, ETH Zurich, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2901-7036
  5. Dagmar Iber

    D-BSSE, ETH Zurich, Basel, Switzerland
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8051-1035


Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CRSII5_170930)

  • Dagmar Iber

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


Animal experimentation: Permission to use animals was obtained from the veterinary office of the Canton Basel-Stadt (licensenumber 2777/26711). Experimental procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Ethics Committee for Animal Care of ETH Zurich.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Publication history

  1. Received: March 5, 2021
  2. Accepted: September 27, 2021
  3. Accepted Manuscript published: October 5, 2021 (version 1)


© 2021, Gomez 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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