Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homolog Eip75B in Drosophila

  1. Lisa Zipper
  2. Denise Jassmann
  3. Sofie Burgmer
  4. Bastian Görlich
  5. Tobias Reiff  Is a corresponding author
  1. Heinrich-Heine-Universitaet, Germany

Abstract

Developmental studies revealed fundamental principles on how organ size and function is achieved, but less is known about organ adaptation to new physiological demands. In fruit flies, juvenile hormone (JH) induces intestinal stem cell (ISC) driven absorptive epithelial expansion balancing energy uptake with increased energy demands of pregnancy. Here, we show 20-Hydroxy-Ecdysone (20HE)-signaling controlling organ homeostasis with physiological and pathological implications. Upon mating, 20HE titer in ovaries and hemolymph are increased and act on nearby midgut progenitors inducing Ecdysone-induced-protein-75B (Eip75B). Strikingly, the PPARγ-homologue Eip75B drives ISC daughter cells towards absorptive enterocyte lineage ensuring epithelial growth. To our knowledge, this is the first time a systemic hormone is shown to direct local stem cell fate decisions. Given the protective, but mechanistically unclear role of steroid hormones in female colorectal cancer patients, our findings suggest a tumor-suppressive role for steroidal signaling by promoting postmitotic fate when local signaling is deteriorated.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided in a separate Excel File.

Article and author information

Author details

  1. Lisa Zipper

    Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Denise Jassmann

    Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Sofie Burgmer

    Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Bastian Görlich

    Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Tobias Reiff

    Institute of Genetics, Heinrich-Heine-Universitaet, Düsseldorf, Germany
    For correspondence
    reifft@hhu.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6610-6148

Funding

Deutsche Forschungsgemeinschaft (RE 34532-1)

  • Tobias Reiff

Wilhelm Sander-Stiftung (2018.145.1)

  • Lisa Zipper

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

Reviewing Editor

  1. Elisabeth Knust, Max-Planck Institute of Molecular Cell Biology and Genetics, Germany

Publication history

  1. Received: February 6, 2020
  2. Accepted: August 7, 2020
  3. Accepted Manuscript published: August 10, 2020 (version 1)
  4. Version of Record published: August 20, 2020 (version 2)
  5. Version of Record updated: January 28, 2021 (version 3)

Copyright

© 2020, Zipper 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. Lisa Zipper
  2. Denise Jassmann
  3. Sofie Burgmer
  4. Bastian Görlich
  5. Tobias Reiff
(2020)
Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARγ-homolog Eip75B in Drosophila
eLife 9:e55795.
https://doi.org/10.7554/eLife.55795

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