Control of chemokine-guided cell migration by ligand sequestration

Primordial germ cell (PGC) migration in zebrafish is directed by the chemokine SDF-1a that activates its receptor CXCR4b. Little is known about the molecu-lar mechanisms controlling the distribution of this chemoattractant in vivo.We demonstrate that the ac-tivity of a second SDF-1/CXCL12 receptor, CXCR7, is crucial for proper migration of PGCs toward their tar-gets. We show that CXCR7 functions primarily in the somatic environment rather than within the migrating cells. In CXCR7 knocked-down embryos, the PGCs exhibit a phenotype that signifies defects in SDF-1a gradient formation as the cells fail to polarize effec-tively and tomigrate toward their targets. Indeed, so-matic cells expressing CXCR7 show enhanced inter-nalization of the chemokine suggesting that CXCR7 acts as a sink for SDF-1a, thus allowing the dynamic changes in the transcription of sdf-1a to be mirrored by similar dynamics at the protein level