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Levayer Lab

@levayerr.bsky.social
3.5K followers 503 following 251 posts

Epithelial cell death, cell extrusion, self-organisation, mechanotransduction and many other things

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Levayer Lab @levayerr.bsky.social · 23/09/2026
Can we now use it to "bias" apoptosis ? We performed a very mild activation of optocaspase in clones and let them develop. Cells in the clones were 3x more likely to die compared to neighbouring cells, suggesting that this previous priming sensitise them to "later" developmental caspase activation.
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Levayer Lab @levayerr.bsky.social · 23/09/2026
So can we predict who among neighbours will be the first ? Using time serie forest (machine learning adapted to use temporal features) we could predict in close to 80% of the case who will the first using relative present and past caspase activity among neighbours
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Levayer Lab @levayerr.bsky.social · 23/09/2026
This also explains a good deal of cell to cell heterogeneity. Accordingly, the cells that are more likely to die upon a pulse of optogenetic caspases are the one that were already exposed in the past.
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Levayer Lab @levayerr.bsky.social · 23/09/2026
Can we go back to the previous experiment and explain the heterogeneity we observed ? Actually the domain of high sensitivity revealed by the global pulse of caspase are mostly explained by the history of cells. Doing the same expt. after "erasing" past caspase removed most of the spatial bias.
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Levayer Lab @levayerr.bsky.social · 23/09/2026
In other words, cells already exposed to caspase in the last 3-5 hours die at lower caspase activity. We used again the optogenetic caspase to validate this prediction using pulses of activation separated in time comparing contralateral regions exposed 1 or 2 times and confirming the "priming"
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Levayer Lab @levayerr.bsky.social · 23/09/2026
So what explains then this heterogeneity ? We looked systematically at geometrical/signaling/spatial features that may correlate with the caspase activity at which cells engage in apoptosis. The correlation matrix you see below outlines a clear neg. correlation with past caspase activation.
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Levayer Lab @levayerr.bsky.social · 23/09/2026
Not only we found cell to cell differences, but also global spatial pattern of caspase sensitivity. Using an optogenetic caspase that we previously developed (optoDronc) and doing mild global activation revealed zones much more sensitive to caspases.
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Levayer Lab @levayerr.bsky.social · 23/09/2026
We checked this in the Drosophila pupal notum segmenting ~20,000 cells and checking systematically at which caspase activity cells engage in cell extrusion and cell death. Using the "derivative" of the GC3Ai caspase sensor was quite predictive but revealed a large heterogeneity of thresholds
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Levayer Lab @levayerr.bsky.social · 23/09/2026
Not every cell react the same way to caspase activation. In our recent study (led by @tomcumming.bsky.social and initiated by @avillars.bsky.social ), we tried to better understand what explains this difference and outlined a role of past caspase exposure 👇 www.nature.com/articles/s41...
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Levayer Lab @levayerr.bsky.social · 08/09/2026
Institut Curie, Paris, symposium: Where Form Takes Shape October 27-28th 2026 (after the yearly International Developmental Biology course) Registration before October 10th (for free !): docs.google.com/forms/d/e/1F... There will be short talks and posters selected from abstracts.
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Levayer Lab @levayerr.bsky.social · 04/09/2026
📢master or PhD student interested in cell biology ? There are spots left for the Molecular Biology of the Cell course @pasteur.fr. Check the amazing list of lecturers + 1 week practical pocking choano cytokeleton with @thibautbrunet.bsky.social team. Registration 👇 www.pasteur.fr/fr/nous-conn...
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Levayer Lab @levayerr.bsky.social · 09/08/2026
With a bit of delay, a little report on the great scientific get together we got in April on cell extrusion #CellExit#1. Have look if you want to get a rapid overview of ongoing projects More to come in the near future with a broader meeting hopefully ! journals.biologists.com/jcs/article/...
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Levayer Lab @levayerr.bsky.social · 06/07/2026
We found, not so surprisingly, that the transient induction of apoptosis is sufficient to lenghten the larval/growth phase. This is driven by JNK induction in dying cells, which is also triggering the well known relaxin hormone Dilp8 (which controls Ecdyson and larval to pupal transition).
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Levayer Lab @levayerr.bsky.social · 06/07/2026
We found a proliferative index that seems higher, but this is actually explained by the relative small size of wing and the higher proliferative index in smaller/younger wing disc (and if one compare proliferation rate for control and apoptosis disc of similar size, there was not difference).
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Levayer Lab @levayerr.bsky.social · 06/07/2026
We assess more globally how proliferation may evolve over time. The first striking feature we found is a net reduction of wing disc size right after apoptosis induction (30% decrease) which cannot be explained by the amount of dying cells (~5%).
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Levayer Lab @levayerr.bsky.social · 06/07/2026
Yet, using quite refine quantitative measurement of adult wing size, we found that adult wing could still recover their normal size and cell number. So...what is then happening here ?
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Levayer Lab @levayerr.bsky.social · 06/07/2026
We wanted to check more carefully whether local induction of death was indeed associated with a local response. Using Drosophila wing disc, mild induction of apoptosis in clones (~5% of cell dying), and spatial statistics, we surprisngly never found clear local increase of prolif near apoptosis
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Levayer Lab @levayerr.bsky.social · 23/06/2026
I missed the chance to meet fly colleagues at the EMBO Crete meeting, but I am also enjoying very much the #Cellmodelinginspaceantime @cshlnews.bsky.social (and the current 21°C...). Exciting modeling and quantitative approches all other the place !
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Levayer Lab @levayerr.bsky.social · 19/06/2026
Studying viola seed sequential balistic popping (driven by dessication) to generate zipping actuator. A nice example of bioinspired design www.science.org/doi/10.1126/...
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Levayer Lab @levayerr.bsky.social · 18/04/2026
That's a wrap ! Beautiful science, lively discussions and a really amazing community, it was a real pleasure to organise with @magalisuzanne.bsky.social this first cell extrusion meeting #CellExIt1. Looking forward number 2 !
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Levayer Lab @levayerr.bsky.social · 10/03/2026
Had a wonderfull time in Bern @institute fur zellbiologie 9 years after leaving the place at the end of my postdoc. Impressive system biology and quantitative approaches from @olivierpertz.bsky.social group, maybe I should go back for a 2nd postdoc...🤔
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Levayer Lab @levayerr.bsky.social · 21/01/2026
That's it...that's my post, period.
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Levayer Lab @levayerr.bsky.social · 26/11/2025
Probably the most intimidating ceremony I have ever been to...but glad of this recognition from the @academiesciences.bsky.social for the CDEH team ! (and yes I am wearing a suit...).
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Levayer Lab @levayerr.bsky.social · 15/10/2025
Just had wonderful 3 days of science and connection in Nîmes for our joint lab retreat with @leopoldlab.bsky.social , Laura Boulan lab and @argo-mkhrji.bsky.social. A lots of brainstorming on growth regulation, robustness, plasticity and the future of drosophila (with hopf bifurcations in between)
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Levayer Lab @levayerr.bsky.social · 09/10/2025
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
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Levayer Lab @levayerr.bsky.social · 09/10/2025
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)
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Levayer Lab @levayerr.bsky.social · 09/10/2025
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)
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Levayer Lab @levayerr.bsky.social · 09/10/2025
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)
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Levayer Lab @levayerr.bsky.social · 09/10/2025
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.
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Levayer Lab @levayerr.bsky.social · 09/10/2025
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
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Levayer Lab @levayerr.bsky.social · 09/10/2025
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...
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Levayer Lab @levayerr.bsky.social · 09/09/2025
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...
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Levayer Lab @levayerr.bsky.social · 21/05/2025
Moreover, sublethal activation of caspase in a clone will actually increase significantly its probability to die later if caspase gets activated later during development.
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Levayer Lab @levayerr.bsky.social · 21/05/2025
Yes ! We found that the cells more likely to die following a pulse of caspase are the one that cumulated more past exposure
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Levayer Lab @levayerr.bsky.social · 21/05/2025
Can we go back to the spatial heterogeneity and explain it ? We found that the spatial pattern of caspase sensitivity is mostly explained by the history of cells and their previous exposure to caspase (compare green signal=cumulative past caspase, and the map of induced death by opto Caspase)
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Levayer Lab @levayerr.bsky.social · 21/05/2025
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)
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Levayer Lab @levayerr.bsky.social · 21/05/2025
We used our large dateset of tracked cells (close to 20,000) to find putative correlation between single cell parameter and the caspase level at which cells engage in apoptosis. It turns out that previous caspase activation (see GC3Ai) negatively correlated with caspase threshold few hours later
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Levayer Lab @levayerr.bsky.social · 21/05/2025
Not only is there cell to cell heterogeneity, but a reproducible pattern of susceptiblity to caspase in the tissue which is revealed by global mild pulse of caspase activation using an optogenetic Caspase9 and tracking of death in the tissue
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Levayer Lab @levayerr.bsky.social · 21/05/2025
To make a long story short, we first tried to figure out if specific caspase threshold were associated with commitment in death using Drosophila notum. It turns out that while caspase activity is predictive of engagement, there is a huge diveristy of thresholds between cells (2 orders of magnitude).
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Levayer Lab @levayerr.bsky.social · 21/05/2025
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...
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Levayer Lab @levayerr.bsky.social · 03/03/2025
I am not panicking...but...😱
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Levayer Lab @levayerr.bsky.social · 17/01/2025
Today, we had our yearly group "explorative meeting" where we discussed broader subjects related to science at large. We started with a discussion around the conditions leading to the emergence of new projects, and then discussed the now famous "why most research is wrong"
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Levayer Lab @levayerr.bsky.social · 14/01/2025
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...
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Levayer Lab @levayerr.bsky.social · 13/01/2025
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)
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Levayer Lab @levayerr.bsky.social · 13/01/2025
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)
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Levayer Lab @levayerr.bsky.social · 13/01/2025
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).
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Levayer Lab @levayerr.bsky.social · 13/01/2025
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).
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Levayer Lab @levayerr.bsky.social · 13/01/2025
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)
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Levayer Lab @levayerr.bsky.social · 13/01/2025
We previously showed that Ras activation in clones could eliminate cells by triggering compaction through growth. Checking more in details, we found striking sorting behaviour that also seemed to contribute to cell deformation (Ras cells in purple, WT in the middle)
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Levayer Lab @levayerr.bsky.social · 13/01/2025
How oncogenic clones can eliminate their neighbours to take over space ? There are different ways combining growth and interfacial tension induced compaction. Check out our latest preprint led by Léo Valon and Alexis Matamoro-Vidal to learn more about this 👇 www.biorxiv.org/content/10.1...
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