Year: 2023
Type: article
Abstract: During development, the rate of tissue growth is determined by the relative balance of cell division and cell death. Cell competition is a fitness quality-control mechanism that contributes to this balance by eliminating viable cells that are less fit than their neighbours. The mutations that confer cells with a competitive advantage and the dynamics of the interactions between winner and loser cells are not well understood. Here, we show that embryonic cells lacking the tumour suppressor p53 are 'super-competitors' that eliminate their wild-type neighbours through the direct induction of apoptosis. This elimination is context dependent, as it does not occur when cells are pluripotent and it is triggered by the onset of differentiation. Furthermore, by combining mathematical modelling and cell-based assays we show that the elimination of wild-type cells is not through competition for space or nutrients, but instead is mediated by short-range interactions that are dependent on the local cell neighbourhood. This highlights the importance of the local cell neighbourhood and the competitive interactions within this neighbourhood for the regulation of proliferation during early embryonic development.
Source: Development
DOI: 10.1242/dev.202503
Authors: Salvador Perez Montero, Pranab K. Paul, Aida di Gregorio, Sarah Bowling, Solomon Shepherd, Nadia J. Fernandes, Ana Lima, Rubén Pérez-Carrasco, Tristan A. Rodriguez
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: European Molecular Biology Organization, Wellcome Trust, UK Research and Innovation, National Institute for Health and Care Research, Imperial College London, Horizon 2020 Framework Programme, Medical Research Council, Biotechnology and Biological Sciences Research Council, NIHR Imperial Biomedical Research Centre, H2020 Marie Skłodowska-Curie Actions
Awards: G1025397761, G1642074453, A Superresolution microscope for biological research in the multi-user Microscopy Facility [FILM]: ALERT 13, FILM microscopy facility: New generation confocal and high content screening microscopes, and upgrades for intravital microscopy., Unravelling the pathways that mediate cell competition during embryonic differentiation, FILM microscopy facility: New generation confocal and high content screening microscopes, and upgrades for intravital microscopy., G2948680474, G3165519751, G3457721854, G370930089, Unravelling the mechanisms regulating cellular fitness during embryonic development, G44043235, Mitochondrial Dynamics in the Control of the Pluripotent States, G5374962834, Understanding the mechanisms of aneuploid cell elimination during early mammalian development, G6501379603, G6566734513, G8440930076, Mechanisms regulating the timing of developmental events in the early mouse embryo
OpenAlex ID: W4390104496