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Pulsatile contractions promote apoptotic cell extrusion in epithelial tissues
Current Biology ( IF 8.1 ) Pub Date : 2021-01-04 , DOI: 10.1016/j.cub.2020.12.005
Youmna Atieh 1 , Thomas Wyatt 2 , Ana Maria Zaske 3 , George T Eisenhoffer 4
Affiliation  

Extrusion is a mechanism used to eliminate unfit, excess, or dying cells from epithelial tissues. The initial events guiding which cells will be selectively extruded from the epithelium are not well understood. Here, we induced damage in a subset of epithelial cells in the developing zebrafish and used time-lapse imaging to examine cell and cytoskeletal dynamics leading to extrusion. We show that cell extrusion is preceded by actomyosin contractions that are pulsatile. Our data show that pulsatile contractions are induced by a junctional to medial re-localization of myosin. Analysis of cell area during contractions revealed that cells pulsing with the longest duration and highest amplitude undergo progressive area loss and extrude. Although pulses were driven by local increases in tension, damage to many cells promoted an overall decrease in the tensile state of the epithelium. We demonstrate that caspase activation leads to sphingosine-1-phosphate enrichment that controls both tissue tension and pulses to dictate areas of extrusion. These data suggest that the kinetics of pulsatile contractions define a key behavioral difference between extruding and non-extruding cells and are predictive of extrusion. Altogether, our study provides mechanistic insight into how localized changes in physical forces are coordinated to remove defective cells for homeostatic maintenance of living epithelial tissues.



中文翻译:

脉动收缩促进上皮组织中的凋亡细胞挤出

挤压是一种用于从上皮组织中消除不合适、过量或垂死细胞的机制。指导哪些细胞将选择性地从上皮中挤出的初始事件尚不清楚。在这里,我们在发育中的斑马鱼的上皮细胞亚群中诱导了损伤,并使用延时成像来检查导致挤压的细胞和细胞骨架动力学。我们表明,细胞挤出之前是脉动的肌动球蛋白收缩。我们的数据表明,脉动性收缩是由肌球蛋白的连接到内侧重新定位引起的。对收缩期间细胞面积的分析表明,以最长持续时间和最高振幅脉冲的细胞经历渐进的面积损失和挤压。尽管脉冲是由局部张力增加驱动的,许多细胞的损伤促进了上皮细胞拉伸状态的整体下降。我们证明 caspase 激活导致 1-磷酸鞘氨醇富集,控制组织张力和脉冲以指示挤出区域。这些数据表明,脉动收缩的动力学定义了挤出和非挤出细胞之间的关键行为差异,并且可以预测挤出。总而言之,我们的研究提供了有关如何协调物理力的局部变化以去除有缺陷的细胞以维持活上皮组织的稳态维持的机械洞察力。这些数据表明,脉动收缩的动力学定义了挤出和非挤出细胞之间的关键行为差异,并且可以预测挤出。总而言之,我们的研究提供了有关如何协调物理力的局部变化以去除有缺陷的细胞以维持活上皮组织的稳态维持的机械洞察力。这些数据表明,脉动收缩的动力学定义了挤出和非挤出细胞之间的关键行为差异,并且可以预测挤出。总而言之,我们的研究提供了有关如何协调物理力的局部变化以去除有缺陷的细胞以维持活上皮组织的稳态维持的机械洞察力。

更新日期:2021-01-04
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