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E-钙黏蛋白在形态发生组织流动前后调节组织力学行为。

E-cadherin tunes tissue mechanical behavior before and during morphogenetic tissue flows.

机构信息

Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA.

Department of Mechanical Engineering, Columbia University, New York, NY 10027, USA.

出版信息

Curr Biol. 2024 Aug 5;34(15):3367-3379.e5. doi: 10.1016/j.cub.2024.06.038. Epub 2024 Jul 15.

Abstract

Adhesion between epithelial cells enables the remarkable mechanical behavior of epithelial tissues during morphogenesis. However, it remains unclear how cell-cell adhesion influences mechanics in both static and dynamically flowing confluent epithelial tissues. Here, we systematically modulate E-cadherin-mediated adhesion in the Drosophila embryo and study the effects on the mechanical behavior of the germband epithelium before and during dramatic tissue remodeling and flow associated with body axis elongation. Before axis elongation, we find that increasing E-cadherin levels produces tissue comprising more elongated cells and predicted to be more fluid-like, providing reduced resistance to tissue flow. During axis elongation, we find that the dominant effect of E-cadherin is tuning the speed at which cells proceed through rearrangement events. Before and during axis elongation, E-cadherin levels influence patterns of actomyosin-dependent forces, supporting the notion that E-cadherin tunes tissue mechanics in part through effects on actomyosin. Notably, the effects of ∼4-fold changes in E-cadherin levels on overall tissue structure and flow are relatively weak, suggesting that the system is tolerant to changes in absolute E-cadherin levels over this range where an intact tissue is formed. Taken together, these findings reveal dual-and sometimes opposing-roles for E-cadherin-mediated adhesion in controlling tissue structure and dynamics in vivo, which result in unexpected relationships between adhesion and flow in confluent tissues.

摘要

上皮细胞之间的黏附使上皮组织在形态发生过程中具有显著的力学行为。然而,细胞-细胞黏附如何影响静态和动态流动的上皮组织的力学特性仍不清楚。在这里,我们系统地调节果蝇胚胎中的 E-钙黏蛋白介导的黏附,并研究其对戏剧性组织重塑和与身体轴伸长相关的流动之前和期间的原肠胚上皮机械行为的影响。在轴伸长之前,我们发现增加 E-钙黏蛋白水平会产生包含更多拉长细胞的组织,并且预测更具流动性,从而降低对组织流动的阻力。在轴伸长过程中,我们发现 E-钙黏蛋白的主要作用是调整细胞通过重排事件的速度。在轴伸长之前和期间,E-钙黏蛋白水平影响肌动球蛋白依赖性力的模式,支持 E-钙黏蛋白通过对肌动球蛋白的影响来调节组织力学的观点。值得注意的是,E-钙黏蛋白水平约 4 倍的变化对整体组织结构和流动的影响相对较弱,这表明在形成完整组织的范围内,系统对 E-钙黏蛋白水平的绝对变化具有耐受性。总之,这些发现揭示了 E-钙黏蛋白介导的黏附在控制体内组织结构和动力学中的双重作用,有时甚至是相反的作用,这导致了在融合组织中黏附与流动之间的意外关系。

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