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

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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.