The role glycosaminoglycans in controlling in vivo chemokine gradient formation, receptor activation and directed migration

斑马鱼的原始生殖细胞（PGC）迁移是由激活其受体CXCR4b的趋化因子SDF-1a引导的。这一发育过程可作为在活胚胎环境下趋化因子引导的细胞迁移的可访问模型。尽管关于SDF- 1a介导的受体激活转化为定向迁移的知识相对详细，但控制化学引诱剂在体内分布的分子机制以及与糖胺聚糖（GAGs）相互作用对受体激活的意义在很大程度上是未知的。本文提出的研究旨在通过糖胺聚糖对SDF-1a分布的影响以及该趋化因子对受体激活的影响来确定糖胺聚糖在控制生殖细胞迁移中的作用。这些发现的功能意义将通过体外和体内实验来检验，其中SDF-1a和gag之间的相互作用对指导细胞迁移的影响将被测试。

Primordial germ cell (PGC) migration in zebrafish is guided by the chemokine SDF-1a that activates its receptor CXCR4b. This developmental process serves as an accessible model for chemokine-guided cell migration in the context of the live embryo. Despite the relatively detailed knowledge concerning the translation of SDF- 1a mediated receptor activation into directed migration, the molecular mechanisms controlling the distribution of the chemoattractant in vivo and the significance of the interaction with glycosaminoglycans (GAGs) for receptor activation are largely unknown. The research proposed here is aimed at defining the role glycosaminoglycans play in controlling germ cell migration through their effect on the distribution of SDF-1a and on receptor activation by this chemokine. The functional significance of these findings will be examined by in vitro and in vivo experiments in which the effect of the interaction between SDF-1a and GAGs on directing cell migration will be tested.