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

Autor: Cachoux VML; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Balakireva M; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Gracia M; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Bosveld F; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., López-Gay JM; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Maugarny A; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Gaugué I; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., di Pietro F; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Rigaud SU; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Noiret L; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France., Guirao B; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France. Electronic address: boris.guirao@curie.fr., Bellaïche Y; Institut Curie, Université PSL, Sorbonne Université, CNRS UMR3215, INSERM U934, Genetics and Developmental Biology, 75005 Paris, France. Electronic address: yohanns.bellaiche@curie.fr.
Jazyk: angličtina
Zdroj: Current biology : CB [Curr Biol] 2023 Nov 20; Vol. 33 (22), pp. 4807-4826.e6. Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1016/j.cub.2023.09.049
Abstrakt: Geometry is a fundamental attribute of biological systems, and it underlies cell and tissue dynamics. Cell geometry controls cell-cycle progression and mitosis and thus modulates tissue development and homeostasis. In sharp contrast and despite the extensive characterization of the genetic mechanisms of caspase activation, we know little about whether and how cell geometry controls apoptosis commitment in developing tissues. Here, we combined multiscale time-lapse microscopy of developing Drosophila epithelium, quantitative characterization of cell behaviors, and genetic and mechanical perturbations to determine how apoptosis is controlled during epithelial tissue development. We found that early in cell lives and well before extrusion, apoptosis commitment is linked to two distinct geometric features: a small apical area compared with other cells within the tissue and a small relative apical area with respect to the immediate neighboring cells. We showed that these global and local geometric characteristics are sufficient to recapitulate the tissue-scale apoptotic pattern. Furthermore, we established that the coupling between these two geometric features and apoptotic cells is dependent on the Hippo/YAP and Notch pathways. Overall, by exploring the links between cell geometry and apoptosis commitment, our work provides important insights into the spatial regulation of cell death in tissues and improves our understanding of the mechanisms that control cell number and tissue size.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE