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Mosaic gastruloids reveal a temporal restriction for developmental cell competition
Joshua D Frenster1, Stephen Babin2, Pablo Casani-Galdon2
1Department of Medicine and Life Sciences, University Pompeu Fabra, Barcelona, Spain. joshua.frenster@gmail.com.
Nature Cell Biology
|April 1, 2026
Summary
Cell competition eliminates unfit cells during early mammalian development. Gastruloids reveal that p53 levels dictate winner-loser status during a specific developmental window, ensuring embryo integrity.
Area of Science:
- Developmental Biology
- Cell Biology
- Genetics
Background:
- Cell competition is a quality control mechanism crucial for mammalian embryogenesis.
- It involves 'winner' cells outcompeting 'loser' cells based on fitness differences.
Purpose of the Study:
- Investigate cell competition dynamics in mammalian embryogenesis.
- Utilize mouse gastruloids as a 3D model to study this process.
Main Methods:
- Created mosaic mouse gastruloids from embryonic stem cells.
- Introduced Trp53-deficient cells as supercompetitors.
- Utilized heterochronic gastruloids and dynamic p53-degrons.
Main Results:
- Trp53-deficient cells induced apoptosis in neighboring wild-type cells.
- Cell competition occurred during a specific developmental transition stage.
- Relative p53 protein levels determined competitive outcomes within this stage.
Conclusions:
- Gastruloids are a powerful model for studying developmental stage-specific cell competition.
- Acute p53 levels are critical for determining cell fitness and competitive outcomes.
- This process ensures developmental integrity by eliminating suboptimal cells.

