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Publication : P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development.

First Author  Bowling S Year  2018
Journal  Nat Commun Volume  9
Issue  1 Pages  1763
PubMed ID  29720666 Mgi Jnum  J:262852
Mgi Id  MGI:6161055 Doi  10.1038/s41467-018-04167-y
Citation  Bowling S, et al. (2018) P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development. Nat Commun 9(1):1763
abstractText  Ensuring the fitness of the pluripotent cells that will contribute to future development is important both for the integrity of the germline and for proper embryogenesis. Consequently, it is becoming increasingly apparent that pluripotent cells can compare their fitness levels and signal the elimination of those cells that are less fit than their neighbours. In mammals the nature of the pathways that communicate fitness remain largely unknown. Here we identify that in the early mouse embryo and upon exit from naive pluripotency, the confrontation of cells with different fitness levels leads to an inhibition of mTOR signalling in the less fit cell type, causing its elimination. We show that during this process, p53 acts upstream of mTOR and is required to repress its activity. Finally, we demonstrate that during normal development around 35% of cells are eliminated by this pathway, highlighting the importance of this mechanism for embryonic development.
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