Control of epithelial cell layer spreading in zebrafish

斑马鱼上皮细胞层扩散的控制

• 批准号: 215377615
• 负责人: Professor Dr. Stephan Wolfgang Grill
• 金额: --
• 依托单位: Max-Planck-Institut für molekulare Zellbiologie und Genetik (MPI-CBG)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/215377615?language=en
• 关键词: Control; epithelial; cell; layer; spreading

Epithelial cell layer spreading is a common and fundamental process in various developmental and disease-related events, such as dorsal closure in Drosophila and wound healing. In the previous funding period, we have dissected the force-generating mechanisms driving epithelial cell layer spreading during zebrafish gastrulation. Specifically, we showed that spreading of the enveloping cell layer (EVL) over the yolk cell during epiboly is triggered by contraction of the actomyosin cortex forming a band-like structure within the yolk syncytial layer (YSL), a thin cytoplasmic layer on the yolk cell surface close to the margin of the EVL. We could further show that this actomyosin band pulls on the margin of the EVL by two distinct motor activities - a cable-constriction motor and a flow-friction motor. The cable-constriction motor operates via circumferential contraction of the actomyosin band, which couples to the spherical geometry of the yolk sac to pull on the EVL margin, much like a purse string. The flow-friction motor operates via retrograde actomyosin flows within the YSL. These are resisted by friction to adjacent structures and thus directly pull the EVL margin towards the vegetal pole. While these findings provided novel insight into the mechanisms by which the YSL actomyosin band drives EVL epiboly movements, important questions remain as to the initiation of actomyosin band formation within the YSL and the mechanical linkage between EVL and YSL allowing the YSL to pull on the EVL. To address these questions, we have begun to analyze how the EVL at its margin establishes contacts with the underlying YSL, and how this contact formation triggers the band-like accumulation of actomyosin within the YSL. Based on our preliminary observations, we hypothesize that microtubules (MTs) within the YSL promote tight junction (TJ) formation between the YSL and EVL, and that proper formation of these junctions in turn directs actomyosin band assembly within the YSL required for EVL epiboly movements. We will address this hypothesis by an interdisciplinary approach employing methods and tools from developmental biology, cell biology, biophysics and theoretical modeling. We aim to elucidate the interplay between MTs, TJs and the actomyosin network during EVL cell layer spreading. We expect that this approach will provide insight into the mechanisms of force-generation, transduction and mechansensation during epithelial cell layer spreading.

上皮细胞层铺展是各种发育和疾病相关事件中常见的基本过程，例如果蝇的背闭合和伤口愈合。在上一个资助期，我们已经解剖了斑马鱼原肠胚形成过程中驱动上皮细胞层扩散的力产生机制。具体而言，我们发现，在外延的卵黄细胞的包膜细胞层（EVL）的传播是由收缩的肌动球蛋白皮质内形成一个带状结构的卵黄合胞体层（YSL），一个薄的细胞质层上的卵黄细胞表面接近的EVL的边缘触发。我们可以进一步表明，这肌动球蛋白带拉上EVL的边缘由两个不同的电机活动-电缆收缩电机和流动摩擦电机。索收缩马达通过肌动球蛋白带的周向收缩来操作，肌动球蛋白带耦合到卵黄囊的球形几何形状以拉动EVL边缘，就像一个荷包。流动摩擦马达通过YSL内的逆行肌动球蛋白流动来操作。这些通过与相邻结构的摩擦来抵抗，从而直接将EVL边缘拉向植物极。虽然这些研究结果提供了新的见解的机制，YSL肌动球蛋白带驱动EVL外包运动，重要的问题仍然是启动肌动球蛋白带形成内的YSL和EVL和YSL之间的机械联系，使YSL拉上EVL。为了解决这些问题，我们已经开始分析EVL在其边缘如何与潜在的YSL建立联系，以及这种联系的形成如何触发YSL内肌动球蛋白的带状积累。根据我们的初步观察，我们假设，微管（MT）内的YSL促进紧密连接（TJ）之间的YSL和EVL的形成，而这些路口的正确形成反过来又指导肌动球蛋白带组装内的YSL EVL epiboly运动所需的。我们将通过跨学科的方法，采用发育生物学，细胞生物学，生物物理学和理论建模的方法和工具来解决这个假设。我们的目的是阐明在EVL细胞层铺展过程中MTs，TJs和肌动球蛋白网络之间的相互作用。我们希望这种方法将提供洞察力的产生，转导和mechanosensation在上皮细胞层的扩展机制。