Celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish

  1. Chunmei Li
  2. Carrie Barton
  3. Katrin Henke
  4. Jake Daane
  5. Stephen Treaster
  6. Joana Caetano-Lopez
  7. Robyn L Tanguay
  8. Matthew Harris  Is a corresponding author
  1. Harvard Medical School, United States
  2. Oregon State University, United States

Abstract

The use of genetics has been invaluable in defining the complex mechanisms of aging and longevity. Zebrafish, while a prominent model for vertebrate development, have not been used systematically to address questions of how and why we age. In a mutagenesis screen focusing on late developmental phenotypes, we identified a new mutant that displays aging phenotypes at young adult stages. We find that the phenotypes are due to loss-of-function in the non-classical cadherin celsr1a. The premature aging is not associated with increased cellular senescence or telomere length but is a result of a failure to maintain progenitor cell populations. We show that celsr1a is essential for maintenance of stem cell progenitors in late stages. Caloric restriction can ameliorate celsr1a aging phenotypes. These data suggest that celsr1a function helps to mediate stem cell maintenance during maturation and homeostasis of tissues and thus regulates the onset or expressivity of aging phenotypes.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Chunmei Li

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Carrie Barton

    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katrin Henke

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1282-3616
  4. Jake Daane

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephen Treaster

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Joana Caetano-Lopez

    Department of Genetics, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Robyn L Tanguay

    Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Matthew Harris

    Department of Genetics, Harvard Medical School, Boston, United States
    For correspondence
    matthew.harris@childrens.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7201-4693

Funding

Ellison Medical Foundation

  • Matthew Harris

Paul Glenn Foundation

  • Matthew Harris

National Institutes of Health (2R01DE019837-09)

  • Matthew Harris

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of Boston Children's Hospital #3215

Reviewing Editor

  1. John F Rawls, Duke University School of Medicine, United States

Publication history

  1. Received: July 24, 2019
  2. Accepted: January 24, 2020
  3. Accepted Manuscript published: January 27, 2020 (version 1)
  4. Version of Record published: February 10, 2020 (version 2)

Copyright

© 2020, Li 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. Chunmei Li
  2. Carrie Barton
  3. Katrin Henke
  4. Jake Daane
  5. Stephen Treaster
  6. Joana Caetano-Lopez
  7. Robyn L Tanguay
  8. Matthew Harris
(2020)
Celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish
eLife 9:e50523.
https://doi.org/10.7554/eLife.50523

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