Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation

  1. Hiroko Katsuno-Kambe
  2. Jessica L Teo
  3. Robert J Ju
  4. James Hudson
  5. Samantha J Stehbens
  6. Alpha S Yap  Is a corresponding author
  1. The University of Queensland, Australia
  2. QIMR Berghofer Medical Research Institute, Australia

Abstract

Epithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here we focus on understanding cellular mechanisms for elongation, using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this loco-regional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles which were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the ECM, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry-breaking and elongation. This required b1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating loco-regional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.

Data availability

All data generated and analysed in this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1-7.

Article and author information

Author details

  1. Hiroko Katsuno-Kambe

    Division of Cell and Developmental Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0292-3506
  2. Jessica L Teo

    Division of Cell and Developmental Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Robert J Ju

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9850-9803
  4. James Hudson

    QIMR Berghofer Medical Research Institute, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Samantha J Stehbens

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8145-2708
  6. Alpha S Yap

    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia
    For correspondence
    a.yap@uq.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1038-8956

Funding

National Health and Medical Research Council (Fellowship 1136592)

  • Alpha S Yap

National Health and Medical Research Council (GNT1123816)

  • Alpha S Yap

National Health and Medical Research Council (1140090)

  • Alpha S Yap

Australian Research Council (DP19010287)

  • Alpha S Yap

Australian Research Council (190102230)

  • Alpha S Yap

Australian Research Council (FT190100516)

  • Samantha J Stehbens

Snow Medical Fellowship

  • James Hudson

Uehara Memorial Foundation (Postdoctoral fellowship)

  • Hiroko Katsuno-Kambe

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

Reviewing Editor

  1. Matthew Kutys, University of California, San Francisco, United States

Version history

  1. Received: February 26, 2021
  2. Preprint posted: February 28, 2021 (view preprint)
  3. Accepted: October 13, 2021
  4. Accepted Manuscript published: October 18, 2021 (version 1)
  5. Version of Record published: October 27, 2021 (version 2)

Copyright

© 2021, Katsuno-Kambe 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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  1. Hiroko Katsuno-Kambe
  2. Jessica L Teo
  3. Robert J Ju
  4. James Hudson
  5. Samantha J Stehbens
  6. Alpha S Yap
(2021)
Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation
eLife 10:e67915.
https://doi.org/10.7554/eLife.67915

Share this article

https://doi.org/10.7554/eLife.67915

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