Female-biased upregulation of insulin pathway activity mediates the sex difference in Drosophila body size plasticity

  1. Jason W Millington
  2. George P Brownrigg
  3. Charlotte Chao
  4. Ziwei Sun
  5. Paige J Basner-Collins
  6. Lianna W Wat
  7. Bruno Hudry
  8. Irene Miguel-Aliaga
  9. Elizabeth J Rideout  Is a corresponding author
  1. The University of British Columbia, Canada
  2. Universite Nice Sophia Antipolis, France
  3. Imperial College London, United Kingdom

Abstract

Nutrient-dependent body size plasticity differs between the sexes in most species, including mammals. Previous work in Drosophila showed that body size plasticity was higher in females, yet the mechanisms underlying increased female body size plasticity remain unclear. Here, we discover that a protein-rich diet augments body size in females and not males because of a female-biased increase in activity of the conserved insulin/insulin-like growth factor signaling pathway (IIS). This sex-biased upregulation of IIS activity was triggered by a diet-induced increase in stunted mRNA in females, and required Drosophila insulin-like peptide 2, illuminating new sex-specific roles for these genes. Importantly, we show that sex determination gene transformer promotes the diet-induced increase in stunted mRNA via transcriptional coactivator Spargel to regulate the male-female difference in body size plasticity. Together, these findings provide vital insight into conserved mechanisms underlying the sex difference in nutrient-dependent body size plasticity.

Data availability

All data generated in this study are provided in supplementary file 2. All statistical tests and p-values are listed in supplementary file 1. Exact diets used in this study are described in supplementary file 3 for ease of replication. All genotypes used in this study are listed in supplementary file 4. A complete list of primers used in this study is provided in supplementary file 5

Article and author information

Author details

  1. Jason W Millington

    Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. George P Brownrigg

    Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Charlotte Chao

    Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Ziwei Sun

    Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Paige J Basner-Collins

    Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Lianna W Wat

    Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Bruno Hudry

    Faculte des Sciences, Universite Nice Sophia Antipolis, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Irene Miguel-Aliaga

    Faculty of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Elizabeth J Rideout

    Department of Cellular and Physiological Sciences, The University of British Columbia, Vancouver, Canada
    For correspondence
    elizabeth.rideout@ubc.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0012-2828

Funding

Canadian Institutes of Health Research (PJT-153072)

  • Elizabeth J Rideout

Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-04249)

  • Elizabeth J Rideout

Michael Smith Foundation for Health Research (16876)

  • Elizabeth J Rideout

Canada Foundation for Innovation (JELF-34879)

  • Elizabeth J Rideout

H2020 European Research Council (ERCAdG787470)

  • Irene Miguel-Aliaga

European Molecular Biology Organization (aALTF782-2015)

  • Bruno Hudry

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

Reviewing Editor

  1. Jiwon Shim, Hanyang University, Republic of Korea

Publication history

  1. Received: April 28, 2020
  2. Accepted: January 11, 2021
  3. Accepted Manuscript published: January 15, 2021 (version 1)
  4. Version of Record published: February 5, 2021 (version 2)

Copyright

© 2021, Millington 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. Jason W Millington
  2. George P Brownrigg
  3. Charlotte Chao
  4. Ziwei Sun
  5. Paige J Basner-Collins
  6. Lianna W Wat
  7. Bruno Hudry
  8. Irene Miguel-Aliaga
  9. Elizabeth J Rideout
(2021)
Female-biased upregulation of insulin pathway activity mediates the sex difference in Drosophila body size plasticity
eLife 10:e58341.
https://doi.org/10.7554/eLife.58341

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