Wnt-and Glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division

Abstract

The Wnt-pathway is part of a signalling network that regulates many aspects of cell biology. Recently we discovered crosstalk between AMPA/Kainate-type ionotropic glutamate receptors (iGluRs) and the Wnt-pathway during the initial Wnt3a-interaction at the cytonemes of mouse embryonic stem cells (ESCs). Here, we demonstrate that this crosstalk persists throughout the Wnt3a-response in ESCs. Both AMPA- and Kainate-receptors regulate early Wnt3a-recruitment, dynamics on the cell membrane, and orientation of the spindle towards a Wnt3a-source at mitosis. AMPA-receptors specifically are required for segregating cell fate components during Wnt3a-mediated asymmetric cell division (ACD). Using Wnt-pathway component knockout lines, we determine that Wnt co-receptor Lrp6 has particular functionality over Lrp5 in cytoneme formation, and in facilitating ACD. Both Lrp5 and 6, alongside pathway effector β-catenin act in concert to mediate the positioning of the dynamic interaction with, and spindle orientation to, a localized Wnt3a-source. Wnt-iGluR crosstalk may prove pervasive throughout embryonic and adult stem cell signalling.

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. Sergi Junyent

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Joshua C Reeves

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. James LA Szczerkowski1

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Clare L Garcin

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Tung-Jui Trieu

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthew Wilson

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Jethro Lundie-Brown

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Shukry J Habib

    Stem Cells and Regenerative Medicine, King's College London, London, United Kingdom
    For correspondence
    Shukry.habib@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3132-2216

Funding

Wellcome Trust (102513/Z/13/Z)

  • Shukry J Habib

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

Reviewing Editor

  1. Beate Maria Lichtenberger, Medical University of Vienna, Austria

Publication history

  1. Received: June 8, 2020
  2. Accepted: May 21, 2021
  3. Accepted Manuscript published: May 24, 2021 (version 1)
  4. Accepted Manuscript updated: June 2, 2021 (version 2)
  5. Version of Record published: June 4, 2021 (version 3)

Copyright

© 2021, Junyent 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. Sergi Junyent
  2. Joshua C Reeves
  3. James LA Szczerkowski1
  4. Clare L Garcin
  5. Tung-Jui Trieu
  6. Matthew Wilson
  7. Jethro Lundie-Brown
  8. Shukry J Habib
(2021)
Wnt-and Glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division
eLife 10:e59791.
https://doi.org/10.7554/eLife.59791

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