Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division

Abstract

Asymmetric stem cell division is a critical mechanism for balancing self-renewal and differentiation. Adult stem cells often orient their mitotic spindle to place one daughter inside the niche and the other outside of it to achieve asymmetric division. It remains unknown whether and how the niche may direct division orientation. Here we discover a novel and evolutionary conserved mechanism that couples cell polarity to cell fate. We show that the cytokine receptor homolog Dome, acting downstream of the niche-derived ligand Upd, directly binds to the microtubule-binding protein Eb1 to regulate spindle orientation in Drosophila male germline stem cells (GSCs). Dome's role in spindle orientation is entirely separable from its known function in self-renewal mediated by the JAK-STAT pathway. We propose that integration of two functions (cell polarity and fate) in a single receptor is a key mechanism to ensure an asymmetric outcome following cell division.

Article and author information

Author details

  1. Cuie Chen

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  2. Ryan Cummings

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  3. Aghapi Mordovanakis

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  4. Alan J Hunt

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  5. Michael Mayer

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  6. David Sept

    Department of Biomedical Engineering, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
  7. Yukiko M Yamashita

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    For correspondence
    yukikomy@umich.edu
    Competing interests
    Yukiko M Yamashita, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5541-0216

Funding

Howard Hughes Medical Institute

  • Yukiko M Yamashita

National Institute of General Medical Sciences (R01GM07200606)

  • Alan J Hunt
  • Michael Mayer
  • Yukiko M Yamashita

National Institute of General Medical Sciences (R01GM118308)

  • Yukiko M Yamashita

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

Copyright

© 2018, Chen 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. Cuie Chen
  2. Ryan Cummings
  3. Aghapi Mordovanakis
  4. Alan J Hunt
  5. Michael Mayer
  6. David Sept
  7. Yukiko M Yamashita
(2018)
Cytokine receptor-Eb1 interaction couples cell polarity and fate during asymmetric cell division
eLife 7:e33685.
https://doi.org/10.7554/eLife.33685

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https://doi.org/10.7554/eLife.33685