PUBLICATION

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

Authors
Li, C., Barton, C., Henke, K., Daane, J., Treaster, S., Caetano-Lopez, J., Tanguay, R.L., Harris, M.
ID
ZDB-PUB-200128-13
Date
2020
Source
eLIFE   9: (Journal)
Registered Authors
Barton, Carrie, Harris, Matthew, Henke, Katrin, Tanguay, Robyn L.
Keywords
developmental biology, genetics, genomics, zebrafish
MeSH Terms
  • Aging/genetics*
  • Aging, Premature/genetics*
  • Animals
  • Animals, Genetically Modified
  • Cadherins/genetics*
  • Cadherins/metabolism*
  • Female
  • Homeostasis/genetics*
  • Male
  • Mutation/genetics
  • Phenotype
  • Stem Cells/metabolism
  • Zebrafish
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
PubMed
31985398 Full text @ Elife
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.
Genes / Markers
Figures
Figure Gallery
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes