Checking more carefully MyoII and tension, we found that N-cad induction also triggers a downregulation of MyoII and tension in junctions "orthogonal" to the clone boundary (for reasons we don't quite understand yet). Putting this feature in the vertex model fully recapitulate the pattern of death

Alternatively, ectopic expression of N-cad was sufficient to increase boundary tension and could trigger WT or N-cad cell elimination as long as they are located in concave boundary/pockets. Basically, who is eliminated is fully set by the geometry of the interface (if you are in minority you lose)

Can we now find experimental conditions reproducing "pure" growth-driven or interfacial tension driven elimination ? First, activation of Yki/Yap in clones was sufficient to recapitulate all the features of growth driven compaction (no impact of curvature, elongation of cells parallel to long axis)

While both conditions could lead to cell compaction and elimination, clear distinctive features emerge in term of distribution of cell death, relationship with boundary shape and orientation of WT cell in the patch (check the paper to get the list)

So...we have now two contributors to WT cell compaction : growth and interfacial tension. Could we extract distinctive features from these two modes of cell deformation ? Alexis started to explore conditions in vertex model either increasing interfacial tension (below) or by increasing growth.

In this framework, just like the interface between two fluids, the pressure should be proportional to the local curvature. This is exactly what Léo found: WT cells near concave interfaces are more compacted and more likely to be eliminated

Happy to share the last version of our story @currentbiology.bsky.social on the role of interfacial tension in mechanical cell competition led by @leovalon.bsky.social and Alexis Matamoro Vidal
www.sciencedirect.com/science/arti...

Important story dissecting the mechanism of gut cell extrusion using organoids. Local heterogeneity of tension promotes live extrusion and basal relaxation is sufficient to kick the cell out. Nice combination of optogenetics and live imaging to demonstrate this
www.science.org/doi/abs/10.1...

Moreover, sublethal activation of caspase in a clone will actually increase significantly its probability to die later if caspase gets activated later during development.

In other words, cells that were already exposed to caspase before are primed for apoptosis later. Can we confirm that experimentally ? We used again the optoCaspase and found that a region exposed to a first pulse and second one few hours laters is indeed more likely to die (compare blue and red)

Many cells during development are exposed to caspase activation and yet survive. Why some die and not others ? We found out that the memory of previous caspase activation bias significantly later death comitment and bias death distribution and single cell decision
www.biorxiv.org/content/10.1...

And by the way, a very similar process was shown by @tetsuotani.bsky.social to trigger elimination of MDCK cells mutant for the tight junction components ZO1/ZO2: an actomyosin cable compact the mutant, eliminate them and help to maintain tissue sealing
www.biorxiv.org/content/10.1...

We then looked for a condition sufficient to trigger an increase of interfacial tension without affecting growth. This worked very well using ectopic expression of N-cad (as shown before by @pflenne.bsky.social lab) : cell sort out with more death in concave interfaces (in WT or Ncad cells)

Can we now recapitulate this experimentally (Ras being a complex case mixing the two ?). We first found that activation of Yki/YAP in clones could perfectly recapitulate all the features of growth induced compaction (no sorting, homogeneous compaction, cells elongated along the WT patch long axis)

If you now add cell death for a certain area strain threshold, this led to elimination near curved areas in the context of interfacial tension, while more homogenous death distribution in the context of growth (white cells, for different death strain threshold).

This is quite different in the context of growth-induced compaction where the patches is more isotropically compacted, and cells more elongated parallel to clone long axis (movie below showing compaction for different increase of red cell area).

Using 2D vertex model, we first found that as expected increased interfacial tension was sufficient to round up clones, and generate significant compaction near curved interfaces and cells elongated orthogonal to the clone long axis (movie below shows colour coded compaction for increasing tension)