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

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Summary

Cell competition eliminates unfit cells in zebrafish by targeting sonic hedgehog activity. This process, marked by Foxo3, ensures proper tissue development and may prevent age-related diseases.

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Genetics

Background:

  • Cell competition is a known mechanism for eliminating unfit cells, but its physiological roles and mechanisms in vertebrates are not well understood.
  • Universal regulators of diverse cell competition remain elusive, hindering a comprehensive understanding of this fundamental biological process.

Purpose of the Study:

  • To investigate the mechanisms and physiological roles of cell competition in vertebrate development, specifically focusing on spinal cord and muscle patterning in zebrafish.
  • To identify common markers and regulatory pathways involved in various types of cell competition across species.

Main Methods:

  • Utilized in vivo zebrafish imaging to observe cell competition dynamics.
  • Investigated the role of sonic hedgehog activity, cadherin-mediated communication, and the Smad-Foxo3-reactive oxygen species axis in cell elimination.
  • Examined Foxo3 expression as a potential common marker for 'loser' cells in zebrafish and mice.

Main Results:

  • Demonstrated that cell competition eliminates cells with unfit sonic hedgehog activity, ensuring robust spinal cord and muscle patterning in zebrafish.
  • Identified cadherin-mediated cell communication and the Smad-Foxo3-reactive oxygen species pathway as key drivers of this elimination process.
  • Established Foxo3 as a conserved marker for loser cells in various cell competition contexts in both zebrafish and mice.

Conclusions:

  • Foxo3-mediated cell competition is crucial for eliminating naturally occurring unfit cells, leading to precise tissue patterning during zebrafish embryogenesis and organogenesis.
  • Cell competition may function as a vital defense system, preventing developmental abnormalities and contributing to adult homeostasis, with implications for age-related diseases linked to Foxo3 downregulation.