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:
上皮细胞之间的粘附使上皮组织在形态发生过程中具有显着的机械行为。然而,目前尚不清楚细胞间粘附如何影响静态和动态流动的融合上皮组织的力学。这里,我们系统地调节果蝇胚胎中E-cadherin介导的粘附,并研究在与体轴伸长相关的剧烈组织重塑和流动之前和期间对胚带上皮力学行为的影响。在轴伸长之前,我们发现,增加E-cadherin水平会产生包含更多细长细胞的组织,并预测会更像流体,提供减少的组织流动阻力。在轴伸长期间,我们发现E-cadherin的主要作用是调节细胞通过重排事件进行的速度。在轴伸长之前和期间,E-钙粘蛋白水平影响肌动球蛋白依赖力的模式,支持E-cadherin部分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-cadherin水平的4倍变化对整体组织结构和血流的影响相对较弱,这表明该系统对在形成完整组织的该范围内的绝对E-cadherin水平的变化具有耐受性。一起来看,这些发现揭示了E-cadherin介导的粘附在体内控制组织结构和动力学方面的双重作用,有时是相反的作用。这导致融合组织中粘连和流动之间的意外关系。