P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development
File(s)s41467-018-04167-y.pdf (2.54 MB)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2018-05-02
Date Acceptance
2018-04-06
Citation
Nature Communications, 2018, 9 (4)
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
9
Issue
4
Copyright Statement
© The Author(s) 2018. This article is licensed under a Creative Commons
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article
’
s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article
’
s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit
http://creativecommons.org/
licenses/by/4.0/
Attribution 4.0 International License, which permits use, sharing,
adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative
Commons license, and indicate if changes were made. The images or other third party
material in this article are included in the article
’
s Creative Commons license, unless
indicated otherwise in a credit line to the material. If material is not included in the
article
’
s Creative Commons license and your intended use is not permitted by statutory
regulation or exceeds the permitted use, you will need to obtain permission directly from
the copyright holder. To view a copy of this license, visit
http://creativecommons.org/
licenses/by/4.0/
Sponsor
British Heart Foundation
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
RE/13/4/30184
MR/N009371/1
MR/P018467/1
Subjects
MD Multidisciplinary
Publication Status
Published
Article Number
ARTN 1763