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.

Metrics

  • 2,423
    Page views
  • 331
    Downloads
  • 13
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Developmental Biology
    2. Evolutionary Biology
    Alexandre P Thiery et al.
    Research Article Updated

    Development of tooth shape is regulated by the enamel knot signalling centre, at least in mammals. Fgf signalling regulates differential proliferation between the enamel knot and adjacent dental epithelia during tooth development, leading to formation of the dental cusp. The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here, we show the conservation and restriction of fgf3, fgf10, and shh to the sites of future dental cusps in the shark (Scyliorhinus canicula), whilst also highlighting striking differences between the shark and mouse. We reveal shifts in tooth size, shape, and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling. In silico modelling of shark dental morphogenesis demonstrates how subtle changes in activatory and inhibitory signals can alter tooth shape, resembling developmental phenotypes and cusp shapes observed following experimental Wnt perturbation. Our results support the functional conservation of an enamel knot-like signalling centre throughout vertebrates and suggest that varied tooth types from sharks to mammals follow a similar developmental bauplan. Lineage-specific differences in signalling are not sufficient in refuting homology of this signalling centre, which is likely older than teeth themselves.

    1. Developmental Biology
    2. Evolutionary Biology
    Sophie Pantalacci
    Insight

    The tooth shape of sharks and mice are regulated by a similar signaling center despite their teeth having very different geometries.