Celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish
- Harvard Medical School, United States
- 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.
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All data generated or analyzed during this study are included in the manuscript and supporting files.
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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
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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Celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish
eLife 9:e50523.
https://doi.org/10.7554/eLife.50523
