PUBLICATION
Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development
- Authors
- Matsumoto, K., Akieda, Y., Haraoka, Y., Hirono, N., Sasaki, H., Ishitani, T.
- ID
- ZDB-PUB-241218-20
- Date
- 2024
- Source
- Nature communications 15: 1066210662 (Journal)
- Registered Authors
- Akieda, Yuki, Haraoka, Yukinari, Ishitani, Tohru
- Keywords
- none
- MeSH Terms
-
- Spinal Cord/cytology
- Spinal Cord/embryology
- Spinal Cord/metabolism
- Body Patterning/genetics
- Cell Competition*
- Forkhead Box Protein O3*/genetics
- Forkhead Box Protein O3*/metabolism
- Zebrafish*/embryology
- Gene Expression Regulation, Developmental
- Organogenesis
- Mice
- Animals
- Reactive Oxygen Species/metabolism
- Embryonic Development
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Hedgehog Proteins/genetics
- Hedgehog Proteins/metabolism
- Signal Transduction
- Cadherins/genetics
- Cadherins/metabolism
- PubMed
- 39690179 Full text @ Nat. Commun.
Citation
Matsumoto, K., Akieda, Y., Haraoka, Y., Hirono, N., Sasaki, H., Ishitani, T. (2024) Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development. Nature communications. 15:1066210662.
Abstract
Unfit cells with defective signalling or gene expression are eliminated through competition with neighbouring cells. However, physiological roles and mechanisms of cell competition in vertebrates remain unclear. In addition, universal mechanisms regulating diverse cell competition are unknown. Using zebrafish imaging, we reveal that cell competition ensures robust patterning of the spinal cord and muscle through elimination of cells with unfit sonic hedgehog activity, driven by cadherin-mediated communication between unfit and neighbouring fit cells and subsequent activation of the Smad-Foxo3-reactive oxygen species axis. We identify Foxo3 as a common marker of loser cells in various types of cell competition in zebrafish and mice. Foxo3-mediated physiological cell competition is required for eliminating various naturally generated unfit cells and for the consequent precise patterning during zebrafish embryogenesis and organogenesis. Given the implication of Foxo3 downregulation in age-related diseases, cell competition may be a defence system to prevent abnormalities throughout development and adult homeostasis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping