WP1. The experienced researcher (ER) has characterized the correlation/causality between cell mechanics and the probability to engage in apoptosis at the mesoscale level (5-50um) via the activity of EGFR/ERK pathway. He especially observed that tissue stretching/compaction triggers an increase/decrease in ERK activity. At a cellular scale, he quantified that more than 70% of cell death is associated to a sudden decrease in ERK activity. This has been published in a research article (Moreno, Valon et al. Current Biology, 2019). This work is at the origin of a technical paper and of the creation of an open source FiJi plugin (Herbert*, Valon* et al., BMC Biology, accepted 2021; gitlab.pasteur.fr/iah-public/localzprojector).
Beyond but related to WP1, the quantification of ERK activity brought some extra and related information. The ER especially demonstrated that spatiotemporal death distribution is bias. He proved that the probability of death in the first neighbours of a dying cells is reduced by 50% via a burst of ERK activity. This in turns protects the tissue from multiple cell death at the same time which could endanger tissue sealing and integrity. Last but not least, many cues are supporting the idea that cell stretching at the cell level is the trigger of these bursts. This work has been published in a research article (Valon et al., Developmental Cell 2021) and presented in six conferences with abstract submission.
In the context of mechanical cell competition, the ER worked on the idea that it can lead to two final scenarios, either the expansion of the oncogenic population or its elimination at the first stage. WP2 was based on the description of mechanical cell competition generated at the border of RasV12 clones in the drosophila pupal notum. The ER reproduced these data and tested extensively six other genetic conditions known to have putative effect on the regulation of cell size, cell contractility, cell proliferation and cell death. While mechanical cell death triggered via the formation of RasV12 seems to be an intricate mixture of cell resistance to cell death, cell growth, cell proliferation and cell tension at the boundary, the ER managed to uncouple cell growth/proliferation from cell tension in two different genetic conditions. Thus, he obtained experimentally some sufficient conditions at the origin of mechanical cell death. The goal of WP3 was to include in in silico simulations, information extracted from experiments to establish phase diagrams of clone disappearance versus invasion as a function of their initial size, shape, and mechanical competition process in game. These experiments are currently being reproduces and analysed and will be published in a research article (in preparation, first submission planned for early 2022). This work is as well at the origin of a review article (Valon, Levayer, Biology of the Cell, 2019).
