| RRC ID |
82856
|
| Author |
Matsumoto K, Akieda Y, Haraoka Y, Hirono N, Sasaki H, Ishitani T.
|
| Title |
Foxo3-mediated physiological cell competition ensures robust tissue patterning throughout vertebrate development.
|
| Journal |
Nat Commun
|
| 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.
|
| Volume |
15(1)
|
| Pages |
10662
|
| Published |
2024-12-17
|
| DOI |
10.1038/s41467-024-55108-x
|
| PII |
10.1038/s41467-024-55108-x
|
| PMID |
39690179
|
| PMC |
PMC11652645
|
| MeSH |
Animals
Body Patterning / genetics
Cadherins / genetics
Cadherins / metabolism
Cell Competition*
Embryonic Development
Forkhead Box Protein O3* / genetics
Forkhead Box Protein O3* / metabolism
Gene Expression Regulation, Developmental
Hedgehog Proteins / genetics
Hedgehog Proteins / metabolism
Mice
Organogenesis
Reactive Oxygen Species / metabolism
Signal Transduction
Spinal Cord / cytology
Spinal Cord / embryology
Spinal Cord / metabolism
Zebrafish* / embryology
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism
|
| IF |
12.121
|
| Resource |
| Zebrafish |
Krt4p:Gal4 |
