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）迁移由激活其受体CXCR 4 b的趋化因子SDF-1a引导。这个发育过程作为一个可行的模型，在活胚胎的情况下，趋化因子引导的细胞迁移。尽管关于SDF- 1a介导的受体活化转化为定向迁移的知识相对详细，但控制体内化学引诱物分布的分子机制以及与糖胺聚糖（GAG）相互作用对受体活化的意义在很大程度上是未知的。本文提出的研究旨在确定糖胺聚糖通过其对SDF-1a分布和该趋化因子对受体活化的影响在控制生殖细胞迁移中发挥的作用。这些发现的功能意义将通过体外和体内实验进行检查，其中将测试SDF-1a和GAG之间的相互作用对指导细胞迁移的影响。

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.