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Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development

Author

Listed:
  • Kanako Matsumoto

    (Osaka University
    Osaka University)

  • Yuki Akieda

    (Osaka University)

  • Yukinari Haraoka

    (Osaka University)

  • Naoki Hirono

    (Osaka University)

  • Hiroshi Sasaki

    (Osaka University)

  • Tohru Ishitani

    (Osaka University
    Osaka University
    Osaka University
    Osaka University)

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.

Suggested Citation

  • Kanako Matsumoto & Yuki Akieda & Yukinari Haraoka & Naoki Hirono & Hiroshi Sasaki & Tohru Ishitani, 2024. "Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55108-x
    DOI: 10.1038/s41467-024-55108-x
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