Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia

  1. Kara L McKinley
  2. Nico Stuurman
  3. Loic A Royer
  4. Christoph Schartner
  5. David Castillo-Azofeifa
  6. Markus Delling
  7. Ophir D Klein  Is a corresponding author
  8. Ronald D Vale  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Chan Zuckerberg Biohub, United States

Abstract

Cell division is essential to expand, shape, and replenish epithelia. In the adult small intestine, cells from a common progenitor intermix with other lineages, whereas cell progeny in many other epithelia form contiguous patches. The mechanisms that generate these distinct patterns of progeny are poorly understood. Using light sheet and confocal imaging of intestinal organoids, we show that lineages intersperse during cytokinesis, when elongated interphase cells insert between apically displaced daughters. Reducing the cellular aspect ratio to minimize the height difference between interphase and mitotic cells disrupts interspersion, producing contiguous patches. Cellular aspect ratio is similarly a key parameter for division-coupled interspersion in the early mouse embryo, suggesting that this physical mechanism for patterning progeny may pertain to many mammalian epithelia. Our results reveal that the process of cytokinesis in elongated mammalian epithelia allows lineages to intermix and that cellular aspect ratio is a critical modulator of the progeny pattern.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Due to their large size (100s of GBs), the source movies are available upon request.

Article and author information

Author details

  1. Kara L McKinley

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6283-9168
  2. Nico Stuurman

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6179-8613
  3. Loic A Royer

    Chan Zuckerberg Biohub, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christoph Schartner

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0599-3956
  5. David Castillo-Azofeifa

    Department of Orofacial Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Markus Delling

    Department of Physiology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ophir D Klein

    Department of Orofacial Sciences, University of California, San Francisco, San Francisco, United States
    For correspondence
    Ophir.Klein@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6254-7082
  8. Ronald D Vale

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    For correspondence
    Ron.Vale@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3460-2758

Funding

Howard Hughes Medical Institute

  • Kara L McKinley
  • Nico Stuurman
  • Ronald D Vale

National Institutes of Health (U01DK103147)

  • Kara L McKinley
  • David Castillo-Azofeifa
  • Ophir D Klein

Chan Zuckerberg Biohub

  • Loic A Royer

Fritz Thyssen Stiftung

  • Christoph Schartner
  • Markus Delling

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

Ethics

Animal experimentation: All experiments involving mice were approved by the Institutional Animal Care and Use Committee of the University of California, San Francisco (protocol #AN151723).

Reviewing Editor

  1. Jody Rosenblatt, University of Utah, United States

Publication history

  1. Received: March 17, 2018
  2. Accepted: June 8, 2018
  3. Accepted Manuscript published: June 13, 2018 (version 1)
  4. Version of Record published: June 28, 2018 (version 2)

Copyright

© 2018, McKinley 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. Kara L McKinley
  2. Nico Stuurman
  3. Loic A Royer
  4. Christoph Schartner
  5. David Castillo-Azofeifa
  6. Markus Delling
  7. Ophir D Klein
  8. Ronald D Vale
(2018)
Cellular aspect ratio and cell division mechanics underlie the patterning of cell progeny in diverse mammalian epithelia
eLife 7:e36739.
https://doi.org/10.7554/eLife.36739
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