Signaling platforms and structures required for cell motility and guided cell migration

对促进细胞运动获得和迁移行为丧失的机制的控制对于器官形态发生、组织修复和维持以及免疫反应等一系列生物过程都很重要。这些过程也与癌症转移和炎症等病理状况有关。研究这些过程的一个有用的体内模型是原始生殖细胞（PGCs）的迁移。这些细胞执行远距离的单细胞迁移，从它们指定的位置迁移到停止迁移并参与器官形成的区域。在项目的第一部分中，我们描述了细胞从极性状态退出并开始迁移时促进极化的机制。在这个继续项目的申请中，我们建议研究这个过程的另一面，即导致极性丧失的细胞和分子机制。这个问题将在胚胎发育期间进行研究，当细胞在其迁移的几个阶段中经历细胞极性丧失的过程时。建议的工作包括细胞内相关分子分布的分析和操作，信号通路活动的一系列操作和过程的实时成像。总之，这些研究将阐明细胞和发育生物学中一个相对不为人所知的过程——细胞极性的丧失。

The control over the mechanisms facilitating cell motility acquisition, and loss of migratory behavior is important for a range of biological processes such as organ morphogenesis, tissue repair and maintenance and immune response. These processes are also relevant for pathological conditions such as cancer metastasis and inflammation. A useful in vivo model for investigating those processes is the migration of Primordial Germ Cells (PGCs). These cells perform long-range single-cell migration from their site of specification to the region where the cease migrating and participate in organ formation. In the first part of project we have characterized the mechanisms facilitating polarization of cells as they exit from apolar states and start migrating. In this application for continuing the project, we propose to investigate the other side of the process i.e. the cellular and molecular mechanisms that contribute to the loss of polarity. This issue will be investigated during embryonic development, when the cells undergo processes of cell polarity loss during several stages of their migration. The proposed work involves analysis and manipulation of the distribution of relevant molecules within the cells, a range of manipulations in the activity of signaling pathways and live imaging of the processes. Together, these investigations will shed light on a relatively less understood process in cell and developmental biology – the loss of cell polarity.