S20-03 A new effector, the matrix-metalloproteinase MMP9, is essential for neural crest onset of migration

Primordial germ cell (PGC) migration in zebrafish is directed by the chemokine SDF-1a that activates its receptor CXCR4b. Guided PGC migration in zebrafish thus serves as a model for chemokinedirected cell migration, a process that is relevant for a wide range of events in development, homeostasis and disease. We show that during their migration PGCs generate bleb-like protrusions that are powered by cytoplasmic flow. Using invivo imaging and probes for the distribution of various structural and regulatory components, we found that those protrusions are formed at sites where higher calcium levels induce myosin contraction and separation of the membrane from the cell cortex. As calcium levels are controlled by the activation of CXCR4b by its ligand SDF-1a, the distribution of the chemokine is critical for determining the direction of protrusion formation in PGCs. Little is known about the molecular mechanisms controlling the distribution of this chemoattractant invivo. We demonstrate that the activity of a second SDF-1/CXCL12 receptor, CXCR7, is crucial for proper migration of PGCs toward their targets. 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 effectively and to migrate toward their targets. Indeed, somatic cells expressing CXCR7 show enhanced internalization 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.