Department of Biological Chemistry, Center for Cell Dynamics, Johns Hopkins School of Medicine, 855 North Wolfe Street, Baltimore, Maryland 21205, USA.
Nat Cell Biol. 2010 Dec;12(12):1133-42. doi: 10.1038/ncb2124. Epub 2010 Nov 21.
Understanding how molecular dynamics leads to cellular behaviours that ultimately sculpt organs and tissues is a major challenge not only in basic developmental biology but also in tissue engineering and regenerative medicine. Here we use live imaging to show that the basal surfaces of Drosophila follicle cells undergo a series of directional, oscillating contractions driven by periodic myosin accumulation on a polarized actin network. Inhibition of the actomyosin contractions or their coupling to extracellular matrix (ECM) blocked elongation of the whole tissue, whereas enhancement of the contractions exaggerated it. Myosin accumulated in a periodic manner before each contraction and was regulated by the small GTPase Rho, its downstream kinase, ROCK, and cytosolic calcium. Disrupting the link between the actin cytoskeleton and the ECM decreased the amplitude and period of the contractions, whereas enhancing cell-ECM adhesion increased them. In contrast, disrupting cell-cell adhesions resulted in loss of the actin network. Our findings reveal a mechanism controlling organ shape and an experimental model for the study of the effects of oscillatory actomyosin activity within a coherent cell sheet.
了解分子动力学如何导致细胞行为,最终塑造器官和组织,不仅是基础发育生物学的主要挑战,也是组织工程和再生医学的主要挑战。在这里,我们使用活细胞成像技术显示,果蝇滤泡细胞的基底表面经历了一系列定向的、振荡的收缩,这些收缩由极化的肌动蛋白网络上周期性的肌球蛋白积累驱动。肌动球蛋白收缩的抑制或其与细胞外基质(ECM)的偶联阻断了整个组织的伸长,而收缩的增强则夸大了这种阻断作用。肌球蛋白在每次收缩前以周期性的方式积累,并受到小 GTPase Rho、其下游激酶 ROCK 和细胞质钙的调节。破坏肌动球蛋白细胞骨架和细胞外基质之间的联系,会降低收缩的幅度和周期,而增强细胞-细胞外基质的黏附则会增加收缩的幅度和周期。相比之下,破坏细胞-细胞黏附会导致肌动蛋白网络的丧失。我们的发现揭示了一种控制器官形状的机制,以及一种用于研究连贯细胞层内振荡性肌动球蛋白活性影响的实验模型。