Abstract

Hydrogen peroxide is the preeminent chemical weapon that organisms use for combat. Individual cells rely on conserved defenses to prevent and repair peroxide-induced damage, but whether similar defenses might be coordinated across cells in animals remains poorly understood. Here, we identify a neuronal circuit in the nematode Caenorhabditis elegans that processes information perceived by two sensory neurons to control the induction of hydrogen peroxide defenses in the organism. We found that catalases produced by Escherichia coli, the nematode's food source, can deplete hydrogen peroxide from the local environment and thereby protect the nematodes. In the presence of E. coli, the nematode's neurons signal via TGFβ-insulin/IGF1 relay to target tissues to repress expression of catalases and other hydrogen peroxide defenses. This adaptive strategy is the first example of a multicellular organism modulating its defenses when it expects to freeload from the protection provided by molecularly orthologous defenses from another species.

Data availability

Aligned mRNA-seq read files were made available under Sequence Read Archive (SRA) SUB7234259. All data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated

Article and author information

Author details

  1. Jodie A Schiffer

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Francesco A Servello

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. William R Heath

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Francis Raj Gandhi Amrit

    Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephanie V Stumbur

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Matthias Eder

    Systems Biology Programme, Centre for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Olivier M F Martin

    Systems Biology Programme, Centre for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  8. Sean B Johnsen

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Julian A Stanley

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9193-3791
  10. Hannah Tam

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Sarah J Brennan

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Natalie G McGowan

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Abigail L Vogelaar

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Yuyan Xu

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. William T Serkin

    Biology, Northeastern University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Arjumand Ghazi

    Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Nicholas Edward Stroustrup

    Systems Biology Programme, Centre for Genomic Regulation, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9530-7301
  18. Javier Apfeld

    Biology, Northeastern University, Boston, United States
    For correspondence
    j.apfeld@northeastern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9897-5671

Funding

National Science Foundation (1750065)

  • Javier Apfeld

National Institutes of Health (R01AG051659)

  • Arjumand Ghazi

Northeastern University (Tier 1 award)

  • Javier Apfeld

MEIC Excelencia award (BFU2017-88615-P)

  • Nicholas Edward Stroustrup

the CERCA Programme/Generalitat de Catalunya, and European Research Council under the European Union's Horizon 2020 research and innovation programme (852201)

  • Nicholas Edward Stroustrup

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

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Version history

  1. Received: February 20, 2020
  2. Accepted: April 21, 2020
  3. Accepted Manuscript published: May 5, 2020 (version 1)
  4. Version of Record published: May 11, 2020 (version 2)

Copyright

© 2020, Schiffer 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

  • 4,500
    views
  • 459
    downloads
  • 17
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Jodie A Schiffer
  2. Francesco A Servello
  3. William R Heath
  4. Francis Raj Gandhi Amrit
  5. Stephanie V Stumbur
  6. Matthias Eder
  7. Olivier M F Martin
  8. Sean B Johnsen
  9. Julian A Stanley
  10. Hannah Tam
  11. Sarah J Brennan
  12. Natalie G McGowan
  13. Abigail L Vogelaar
  14. Yuyan Xu
  15. William T Serkin
  16. Arjumand Ghazi
  17. Nicholas Edward Stroustrup
  18. Javier Apfeld
(2020)
Caenorhabditis elegans processes sensory information to choose between freeloading and self-defense strategies
eLife 9:e56186.
https://doi.org/10.7554/eLife.56186

Share this article

https://doi.org/10.7554/eLife.56186

Further reading

    1. Developmental Biology
    Siyuan Cheng, Ivan Fan Xia ... Stefania Nicoli
    Research Article

    Vascular smooth muscle cells (VSMCs) envelop vertebrate brain arteries and play a crucial role in regulating cerebral blood flow and neurovascular coupling. The dedifferentiation of VSMCs is implicated in cerebrovascular disease and neurodegeneration. Despite its importance, the process of VSMC differentiation on brain arteries during development remains inadequately characterized. Understanding this process could aid in reprogramming and regenerating dedifferentiated VSMCs in cerebrovascular diseases. In this study, we investigated VSMC differentiation on zebrafish circle of Willis (CoW), comprising major arteries that supply blood to the vertebrate brain. We observed that arterial specification of CoW endothelial cells (ECs) occurs after their migration from cranial venous plexus to form CoW arteries. Subsequently, acta2+ VSMCs differentiate from pdgfrb+ mural cell progenitors after they were recruited to CoW arteries. The progression of VSMC differentiation exhibits a spatiotemporal pattern, advancing from anterior to posterior CoW arteries. Analysis of blood flow suggests that earlier VSMC differentiation in anterior CoW arteries correlates with higher red blood cell velocity and wall shear stress. Furthermore, pulsatile flow induces differentiation of human brain PDGFRB+ mural cells into VSMCs, and blood flow is required for VSMC differentiation on zebrafish CoW arteries. Consistently, flow-responsive transcription factor klf2a is activated in ECs of CoW arteries prior to VSMC differentiation, and klf2a knockdown delays VSMC differentiation on anterior CoW arteries. In summary, our findings highlight blood flow activation of endothelial klf2a as a mechanism regulating initial VSMC differentiation on vertebrate brain arteries.

    1. Developmental Biology
    Zhimin Xu, Zhao Wang ... Yingchuan B Qi
    Research Article

    Precise developmental timing control is essential for organism formation and function, but its mechanisms are unclear. In C. elegans, the microRNA lin-4 critically regulates developmental timing by post-transcriptionally downregulating the larval-stage-fate controller LIN-14. However, the mechanisms triggering the activation of lin-4 expression toward the end of the first larval stage remain unknown. We demonstrate that the transmembrane transcription factor MYRF-1 is necessary for lin-4 activation. MYRF-1 is initially localized on the cell membrane, and its increased cleavage and nuclear accumulation coincide with lin-4 expression timing. MYRF-1 regulates lin-4 expression cell-autonomously and hyperactive MYRF-1 can prematurely drive lin-4 expression in embryos and young first-stage larvae. The tandem lin-4 promoter DNA recruits MYRF-1GFP to form visible loci in the nucleus, suggesting that MYRF-1 directly binds to the lin-4 promoter. Our findings identify a crucial link in understanding developmental timing regulation and establish MYRF-1 as a key regulator of lin-4 expression.