Related Experiment Video
Updated: Mar 9, 2026
Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos
Published on: February 22, 2016
p53 pathway is involved in cell competition during mouse embryogenesis
Guoxin Zhang1,2, Yinyin Xie1,2, Ying Zhou1,2
1State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, JiangSu 210061, China.
Abstract:
The function of tumor suppressor p53 has been under intense investigation. Acute stresses such as DNA damage are able to trigger a high level of p53 activity, leading to cell cycle arrest or apoptosis. In contrast, the cellular response of mild p53 activity induced by low-level stress in vivo remains largely unexplored. Murine double minute (MDM)2 and MDM4 are two major negative regulators of p53. Here, we used the strategy of haploinsufficiency of Mdm2 and Mdm4 to induce mild p53 activation in vivo and found that Mdm2+/-Mdm4+/- double-heterozygous mice exhibited normal embryogenesis. However, closer examination demonstrated that the Mdm2+/-Mdm4+/- cells exhibited a growth disadvantage and were outcompeted during development in genetic mosaic embryos that contained wild-type cells. Further study indicated the out-competition phenotype was dependent on the levels of p53. These observations revealed that cells with mild p53 activation were less fit and exhibited altered fates in a heterotypic environment, resembling the cell competition phenomenon first uncovered in Drosophila By marking unfit cells for elimination, p53 may exert its physiological role to ensure organ and animal fitness.
Insights
Mild p53 activation, induced by reduced Mdm2/Mdm4, causes cellular disadvantage. These less fit cells are outcompeted during development, suggesting p53 ensures organism fitness by eliminating weaker cells.
Area of Science:
- Cellular biology
- Tumor suppressor function
- Developmental biology
Background:
- The tumor suppressor p53 is activated by acute stress, inducing cell cycle arrest or apoptosis.
- The in vivo response to mild p53 activation from low-level stress is not well understood.
- Murine double minute (MDM)2 and MDM4 are key negative regulators of p53.
Purpose of the Study:
- To investigate the in vivo consequences of mild p53 activation.
- To explore the role of p53 in cellular fitness and competition under low-level stress.
Main Methods:
- Utilized Mdm2 and Mdm4 haploinsufficiency to induce mild p53 activation in mice.
- Generated genetic mosaic embryos containing both Mdm2+/-Mdm4+/- cells and wild-type cells.
- Analyzed cellular growth, competition, and p53 levels during development.
Main Results:
- Mdm2+/-Mdm4+/- mice showed normal embryogenesis, but their cells exhibited a growth disadvantage.
- Cells with mild p53 activation were outcompeted by wild-type cells in mosaic embryos.
- This out-competition phenotype was dependent on p53 levels.
Conclusions:
- Mild p53 activation leads to reduced cellular fitness and altered cell fates in a competitive environment.
- The findings reveal a role for p53 in cell competition, similar to phenomena observed in Drosophila.
- p53 may function to eliminate unfit cells, thereby ensuring overall organ and animal fitness.
Related Concept Videos
02:23Abnormal Proliferation
01:23Negative Regulator Molecules