The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium

Abstract

In emerging epithelial tissues, cells undergo dramatic rearrangements to promote tissue shape changes. Dividing cells remain interconnected via transient cytokinetic bridges. Bridges are cleaved during abscission and currently, the consequences of disrupting abscission in developing epithelia are not well understood. We show that the Rab GTPase, Rab25, localizes near cytokinetic midbodies and likely coordinates abscission through endomembrane trafficking in the epithelium of the zebrafish gastrula during epiboly. In maternal-zygotic Rab25a and Rab25b mutant embryos, morphogenic activity tears open persistent apical cytokinetic bridges that failed to undergo timely abscission. Cytokinesis defects result in anisotropic cell morphologies that are associated with a reduction of contractile actomyosin networks. This slows cell rearrangements and alters the viscoelastic responses of the tissue, all of which likely contribute to delayed epiboly. We present a model in which Rab25 trafficking coordinates cytokinetic bridge abscission and cortical actin density, impacting local cell shape changes and tissue-scale forces.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Patrick Morley Willoughby

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Molly Allen

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2419-0000
  3. Jessica Yu

    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Roman Korytnikov

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Tianhui Chen

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2236-2224
  6. Yupeng Liu

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Isis So

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6232-2644
  8. Neil Macpherson

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Jennifer A Mitchell

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  10. Rodrigo Fernandez-Gonzalez

    Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0770-744X
  11. Ashley E E Bruce

    Cell and Systems Biology, University of Toronto, Toronto, Canada
    For correspondence
    ashley.bruce@utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0567-2928

Funding

Natural Sciences and Engineering Research Council of Canada (RGPIN-2018-04862)

  • Ashley E E Bruce

Canadian Institutes of Health Research (156279)

  • Rodrigo Fernandez-Gonzalez

Natural Sciences and Engineering Research Council of Canada (RGPIN-2020-05972)

  • Jennifer A Mitchell

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Canadian Council on Animal Care Guidelines on the Care and Use of Fish in Research. All the animals were handled and maintained according to a protocol (Protocol Number: 20012462) approved by the Biological Sciences Local Animal Care Committee at the University of Toronto.

Reviewing Editor

  1. Michel Bagnat, Duke University, United States

Publication history

  1. Received: December 23, 2020
  2. Accepted: March 22, 2021
  3. Accepted Manuscript published: March 23, 2021 (version 1)
  4. Version of Record published: April 9, 2021 (version 2)
  5. Version of Record updated: May 19, 2022 (version 3)

Copyright

© 2021, Willoughby 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. Patrick Morley Willoughby
  2. Molly Allen
  3. Jessica Yu
  4. Roman Korytnikov
  5. Tianhui Chen
  6. Yupeng Liu
  7. Isis So
  8. Neil Macpherson
  9. Jennifer A Mitchell
  10. Rodrigo Fernandez-Gonzalez
  11. Ashley E E Bruce
(2021)
The recycling endosome protein Rab25 coordinates collective cell movements in the zebrafish surface epithelium
eLife 10:e66060.
https://doi.org/10.7554/eLife.66060

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Yang S Chen, Wanfu Hou ... Brian M Zid
    Research Article Updated

    During times of unpredictable stress, organisms must adapt their gene expression to maximize survival. Along with changes in transcription, one conserved means of gene regulation during conditions that quickly repress translation is the formation of cytoplasmic phase-separated mRNP granules such as P-bodies and stress granules. Previously, we identified that distinct steps in gene expression can be coupled during glucose starvation as promoter sequences in the nucleus are able to direct the subcellular localization and translatability of mRNAs in the cytosol. Here, we report that Rvb1 and Rvb2, conserved ATPase proteins implicated as protein assembly chaperones and chromatin remodelers, were enriched at the promoters and mRNAs of genes involved in alternative glucose metabolism pathways that we previously found to be transcriptionally upregulated but translationally downregulated during glucose starvation in yeast. Engineered Rvb1/Rvb2-binding on mRNAs was sufficient to sequester mRNAs into mRNP granules and repress their translation. Additionally, this Rvb tethering to the mRNA drove further transcriptional upregulation of the target genes. Further, we found that depletion of Rvb2 caused decreased alternative glucose metabolism gene mRNA induction, but upregulation of protein synthesis during glucose starvation. Overall, our results point to Rvb1/Rvb2 coupling transcription, mRNA granular localization, and translatability of mRNAs during glucose starvation. This Rvb-mediated rapid gene regulation could potentially serve as an efficient recovery plan for cells after stress removal.