celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish

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 pheno...

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Bibliographic Details
Published in:eLife 2020-01, Vol.9
Main Authors: Li, Chunmei, Barton, Carrie, Henke, Katrin, Daane, Jake, Treaster, Stephen, Caetano-Lopes, Joana, Tanguay, Robyn L, Harris, Matthew P
Format: Article
Language:English
Subjects:
Aging
Aging - genetics
Aging, Premature - genetics
Animals
Animals, Genetically Modified
Cadherins
Cadherins - genetics
Cadherins - metabolism
Developmental Biology
Dietary restrictions
Female
Fish
Genetics and Genomics
Genotype & phenotype
Homeostasis
Homeostasis - genetics
Identification
Laboratories
Male
Mutagenesis
Mutants
Mutation
Mutation - genetics
Phenotype
Phenotypes
planar cell polarity
Progenitor cells
progeria
Senescence
Stem cells
Stem Cells - metabolism
Young adults
Zebrafish
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
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Summary: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 . 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 is essential for maintenance of stem cell progenitors in late stages. Caloric restriction can ameliorate aging phenotypes. These data suggest that function helps to mediate stem cell maintenance during maturation and homeostasis of tissues and thus regulates the onset or expressivity of aging phenotypes.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.50523