关键词: CP: Cell biology CP: Developmental biology calcium cell cycle fluctuating asymmetry morphogenesis

来  源:   DOI:10.1016/j.celrep.2024.114398

Abstract:
Mechanosensitive Piezo channels regulate cell division, cell extrusion, and cell death. However, systems-level functions of Piezo in regulating organogenesis remain poorly understood. Here, we demonstrate that Piezo controls epithelial cell topology to ensure precise organ growth by integrating live-imaging experiments with pharmacological and genetic perturbations and computational modeling. Notably, the knockout or knockdown of Piezo increases bilateral asymmetry in wing size. Piezo\'s multifaceted functions can be deconstructed as either autonomous or non-autonomous based on a comparison between tissue-compartment-level perturbations or between genetic perturbation populations at the whole-tissue level. A computational model that posits cell proliferation and apoptosis regulation through modulation of the cutoff tension required for Piezo channel activation explains key cell and tissue phenotypes arising from perturbations of Piezo expression levels. Our findings demonstrate that Piezo promotes robustness in regulating epithelial topology and is necessary for precise organ size control.
摘要:
机械敏感性压电通道调节细胞分裂,细胞挤压,细胞死亡。然而,Piezo在调节器官发生方面的系统级功能仍然知之甚少。这里,我们证明Piezo通过整合活成像实验与药理学和遗传扰动以及计算模型来控制上皮细胞拓扑以确保精确的器官生长。值得注意的是,压倒或压倒增加了两侧机翼大小的不对称性。基于组织区室级扰动之间或整个组织级遗传扰动群体之间的比较,可以将压电的多方面函数解构为自主或非自主。通过调节压电通道激活所需的截止张力来定位细胞增殖和凋亡调节的计算模型解释了由压电表达水平的扰动引起的关键细胞和组织表型。我们的发现表明,Piezo可促进调节上皮拓扑结构的鲁棒性,并且对于精确控制器官大小是必需的。
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