Cell motility in vivo - polarization of zebrafish germ cells

体内细胞运动——斑马鱼生殖细胞的极化

• 批准号: 173834920
• 负责人: Professor Dr. Erez Raz
• 金额: --
• 依托单位: Institut für Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/173834920?language=en
• 关键词: Cell; motility; vivo; polarization; zebrafish

A central theme in Developmental Biology is the movement of cells and tissues during pattern formation and organogenesis. Determining the molecular and cellular mechanisms facilitating cell polarization and migration in vivo would thus contribute to our understanding of various developmental processes. The migration of zebrafish primordial germ cells serves as an excellent accessible in vivo model for cell migration. The migration path of these cells, the molecules responsible for directing them and some of the cellular mechanisms facilitating cell motility are known. This knowledge will be employed in the proposed research that is aimed at addressing the issue of the acquisition of cell polarity in the context of cell motility. Filopodia are thin cellular extensions containing parallel actin filaments that are often observed on the surface of migratory cells. Whereas filopodia are thought to play a role in cell migration, their precise function in the context of the intact organism is so far unknown. In the course of this study, the distribution and the morphology of filopodia will be monitored during different steps of the migration process (acquisition of motility, directed migration and stop upon arrival at the target). The distribution of different regulators and structural proteins in the filopodia will then be determined at those different phases of migration. In the next step, over-expression or expression of modified protein versions will be used to affect filopodia development (filopodia distribution, length and stability). The effect of alterations in filopodia structure on biochemical pathways (calcium signaling, actin distribution, septin polarization and the activation patterns of RhoGTPases) important for cell motility will be determined. Last, dynamic parameters of cell migration will be compared between wild-type cells and cells in which filopodia development is compromised. Specifically, we will examine the effect of abnormal filopodia on cell migration speed, maintenance of direction and arrival at the target.

发育生物学的一个核心主题是在模式形成和器官发生过程中细胞和组织的运动。因此，确定促进细胞极化和体内迁移的分子和细胞机制将有助于我们对各种发育过程的理解。斑马鱼原始生殖细胞的迁移是用于细胞迁移的体内模型中极好的访问。这些细胞的迁移路径，负责引导它们的分子以及一些促进细胞运动的细胞机制。这些知识将用于拟议的研究中，该研究旨在解决细胞运动中获取细胞极性问题的问题。丝状虫是含有平行肌动蛋白丝的细胞延伸，通常在迁移细胞表面观察到。虽然丝状疾病被认为在细胞迁移中起作用，但在完整生物体的背景下，它们的精确功能迄今未知。在这项研究的过程中，将在迁移过程的不同步骤（获取运动，定向迁移并在到达目标时停止）的不同步骤中监测丝状虫的分布和形态。然后将在迁移的那些不同阶段确定不同调节剂和结构蛋白的分布。在下一步中，修饰蛋白版本的过表达或表达将用于影响丝状发育（丝状分布，长度和稳定性）。将确定对细胞运动重要的生物化学途径（钙信号，肌动蛋白分布，Septin极化和激活模式）对生化途径的影响。最后，将比较细胞迁移的动态参数，在野生型细胞和丝状发育受到损害的细胞之间进行比较。具体而言，我们将研究异常丝状虫对细胞迁移速度，方向维持和到达目标的影响。