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Stem cell competition driven by the Axin2-p53 axis controls brain size during murine development.
Xue-Lian Sun1, Zhen-Hua Chen1, Xize Guo1
1State Key Laboratory of Molecular Development Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China.
Developmental Cell
|April 13, 2023
Summary
Cell competition eliminates unfit neural progenitor cells (NPCs) in the developing brain, regulated by Axin2 and p53 signaling. This pathway optimizes brain size by controlling cell fitness and competition.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Cell competition is a quality-control mechanism essential for organ development.
- The role of cell competition among neural progenitor cells (NPCs) in the developing brain is not well understood.
Purpose of the Study:
- To investigate the existence and mechanisms of cell competition in neural progenitor cells.
- To elucidate the roles of Axin2 and p53 in regulating NPC competition and brain development.
Main Methods:
- Induction of genetic mosaicism in mouse models to study Axin2-deficient and Trp53-deficient NPCs.
- Analysis of apoptotic elimination, cell signaling pathways (p53), and cortical development.
Main Results:
- Endogenous cell competition occurs in NPCs and correlates with Axin2 levels.
- Axin2-deficient NPCs are eliminated via p53-dependent apoptosis, acting as "losers".
- Loss of both Axin2 and Trp53 leads to increased cortical size, indicating their regulatory roles.
Conclusions:
- The Axin2-p53 axis regulates cell fitness and competition among NPCs during brain development.
- This pathway is crucial for optimizing brain size through quality control of neural progenitor cells.
