Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development.
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.
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Research summary
The paper explores the role of Foxo3 in physiological cell competition, which is linked to the elimination of unfit cells during development. This mechanism may have implications for maintaining tissue homeostasis and preventing age-related abnormalities, suggesting a connection to longevity research. However, while the findings are solid and contribute to understanding cellular processes, they do not present a major breakthrough or transformative implications for the field of aging research.
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