Molecular mechanisms controlling germ-cell migration in zebrafish

在许多生物体中，原生殖细胞必须从特定的位置迁移到发育中的性腺，在那里它们产生配子。在这一过程中，原始生殖细胞（PGG）从遥远的起始位置通过体细胞组织到达性腺形成的区域，体细胞组织本身也经历了模式化和细胞运动的过程。因此，PGC是一个很好的模型系统，用于研究允许细胞在复杂的细胞环境中向发育中的胚胎内的特定点导航的机制。在以前的研究中，我们已经详细描述了野生型斑马鱼胚胎中的PGCs从其发育的最早阶段到其到达目标性腺体细胞部分的阶段的迁移过程。这一建议的目的是了解潜在的PGC运动和迁移的引诱剂源的方向的分子机制。为此，我们建议表征从PGC规范的时间到细胞能够表现出运动行为和定向迁移的时间的细胞骨架结构的动态。在此分析之后，将使用显性负性细胞骨架蛋白形式的表达以及通过表达和确定细胞骨架组装调节剂的空间活性来尝试确定不同细胞骨架构型的功能意义。这些测试将提供有关促进细胞运动和引导迁移的机制的重要线索。

In many organisms the promordial germ cells have to migrate from the position where the are specified towards the developing gonad where they generate gametes. In this process the primordial germ cells (PGGs) reach the region where the gonad forms from distant starting positions through somatic tissues that are themselves subjected to processes of patternig and cell movement. The PGCs are therefore an excellent model system for studying the mechanisms that allow cells to navigate through complex cellular environments towards specific points within the developing embryo. In previous studies we have described in detail the migration process of the PGCs in wild-type zebrafish embryos from the earliest stages of their development to the stage when they reach their target, tje somatic part of the gonad. This proposal is aimed at unterstanding the molecular machinery underlying PGC motility and migration in the direction of a source od attractant. To this end, we propose to characterize the dynamics of cytoskeleton architecture from the time of PGC specification to the time when the cells are capable of exhibiting motile behavior and directional migration. Following this analysis attempts to determine the functional significance of different cytoskeleton configurations will be made using expression of dominant negative cytoskeletal proteins forms and by expression and determination of the spatial activity of regulators of cytoskeleton assembly. These tests will provide important clues regarding the mechanisms promoting cell motility and guided migration.