Epithelial apoptotic pattern emerges from global and local regulation by cell apical area

Cachoux, Victoire M.L.; Balakireva, Maria; Gracia, Mélanie; Bosveld, Floris; López-Gay, Jesús M.; Maugarny, Aude; Gaugué, Isabelle; di Pietro, Florencia; Rigaud, Stéphane U.; Noiret, Lorette; Guirao, Boris; Bellaïche, Yohanns

doi:10.1016/j.cub.2023.09.049

Cited by 6 publications

(8 citation statements)

References 126 publications

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“…Thus, cell extrusion appears to be a way to buffer external constraints through the regulation of cell number and as such responds with high sensitivity to mechanical cues. More recently, a tight link between geometrical parameters (area and relative area) and the probability to enter apoptosis was established (Cachoux et al, 2023). This work shows that cells that just divided have a high probability to enter apoptosis and identified Hippo and Notch pathways as sensors of apical surface area or differential area between neighbors, in a fast-growing tissue.…”

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confidence: 80%

Compressive stress drives morphogenetic apoptosis

Merle,

Cazales,

Bouzignac

et al. 2024

Preprint

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Tissues and organs are constantly submitted to physical stress, including compression, stretching, shear stress. These physical constraints can influence fundamental processes such cell division, cell death and cell differentiation. In particular, the impact of compression due to overproliferation and overcrowding has been the focus of a number of recent studies, revealing the importance of mechanics in the regulation of cell number and tissue homeostasis. However, addressing the impact of mechanical challenges in living organisms remains a challenge and how tissue compression impact cell death in the context of morphogenesis is totally unknown. Here we address this question using the drosophila leg disc as a model system. In this model, we showed that a natural compression is exerted by the surrounding tissue or envelope and that this compression is required for the correct morphogenesis of the underlying tissue, the developing leg. In this tissue, apoptosis contributes to the change in tissue shape through the generation of a pulling force on the apical surface. Apoptosis is preferentially localized in the future fold region, induced by the expression of proapoptotic genes. However, only a subset of cells expressing the proapoptotic genes are dying and how this precise pattern of cell death is established is totally unknown. Here, we found that the natural compression exerted by the envelope contributes to the precise regulation of apoptosis, the absence of compression reducing drastically the number of apoptotic events while the presence of high compression increases the number of dying cells. Thus, compression constitutes an integral part of apoptosis regulation during leg morphogenesis. We analyzed the consequences of compression on cell and nuclear geometry and found that compression affects mainly cell anisotropy and nucleus aspect ratio. We further decipher subcellular tension redistribution under compressive stress and revealed an important switch in lateral tension and opening new perspectives in term of mechanotransduction.

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mentioning

confidence: 80%

Compressive stress drives morphogenetic apoptosis

Merle,

Cazales,

Bouzignac

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“… Alternatives: To use an alternative method without the 3D-printed device FlyPress, please refer to Cachoux, Balakireva et al., 2023. 1 …”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…In our previous articles, 1 , 2 we explored the role of mechanics on tissue development by applying forces on the Drosophila notum through a PDMS strip. This step follows an initial flattening of the tissue, which increases the tissue adhesion to the PDMS strip used later to apply the forces.…”

Section: Before You Beginmentioning

confidence: 99%

“…Upon tissue deformation, the dynamics of the tissues can then be monitored with high temporal and spatial resolution, over several hours, making it possible to explore the effects of mechanical forces on long timescales as shown in our previous publications. 1 , 2 Since it is built on the use of a PDMS layer to deform the tissue, it could be easily adapted to numerous samples. Altogether, the StretchCo device paves the way for a large range of experiments to explore the biomechanics of tissues in vivo .…”

Section: Expected Outcomesmentioning

confidence: 99%

“…For additional details on the use and execution of this protocol, please refer to Cachoux et al. (2023) 1 from which the StretchCo machine has been derived.…”

mentioning

confidence: 99%

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