Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, Dresden 01307, Germany; BIOTEC, Technische Universität Dresden, Tatzberg 47/49, Dresden 01307, Germany.
Dev Cell. 2014 Mar 31;28(6):617-32. doi: 10.1016/j.devcel.2014.02.011.
While gastrulation movements offer mechanistic paradigms for how collective cellular movements shape developing embryos, far less is known about coordinated cellular movements that occur later in development. Studying eyelid closure, we explore a case where an epithelium locally reshapes, expands, and moves over another epithelium. Live imaging, gene targeting, and cell-cycle inhibitors reveal that closure does not require overlying periderm, proliferation, or supracellular actin cable assembly. Laser ablation and quantitative analyses of tissue deformations further distinguish the mechanism from wound repair and dorsal closure. Rather, cell intercalations parallel to the tissue front locally compress it perpendicularly, pulling the surrounding epidermis along the closure axis. Functional analyses in vivo show that the mechanism requires localized myosin-IIA- and α5β1 integrin/fibronectin-mediated migration and E-cadherin downregulation likely stimulated by Wnt signaling. These studies uncover a mode of epithelial closure in which forces generated by cell intercalation are leveraged to tow the surrounding tissue.
虽然原肠胚形成运动为细胞集体运动如何塑造胚胎发育提供了机械模型，但对于发育后期发生的协调细胞运动知之甚少。在研究眼睑闭合的过程中，我们探索了一种上皮细胞局部重塑、扩张并迁移到另一个上皮细胞上的情况。活体成像、基因靶向和细胞周期抑制剂的研究表明，闭合并不需要覆盖的表皮细胞、增殖或细胞间超微丝肌动蛋白缆索的组装。激光消融和组织变形的定量分析进一步将其与伤口修复和背侧闭合区分开来。相反，与组织前缘平行的细胞插入局部垂直压缩它，将周围的表皮沿着闭合轴牵拉。体内功能分析表明，该机制需要局部肌球蛋白 IIA 和α5β1 整合素/纤连蛋白介导的迁移，以及 E-钙黏蛋白下调，可能受到 Wnt 信号的刺激。这些研究揭示了一种上皮细胞闭合的模式，其中细胞插入产生的力被用来牵拉周围的组织。
