CD9 tetraspanins convey robustness to CXCR4b signalling during collective cell migration

Collective cell migration is essential for embryonic development and homeostatic processes. During zebrafish development, the posterior lateral line primordium (pLLP) navigates along the embryo flank by collective cell migration. The chemokine receptors, CXCR4b and CXCR7b, as well as their cognate ligand, CXCL12a, are essential for this process. Knockdown of the zebrafish CD9 tetraspanin orthologue, cd9b, displayed mild pLL abnormalities. Through generation of CRISPR mutants, we show that cd9a and cd9b function partially redundantly in pLLP migration, which is delayed in the cd9b single and cd9a; cd9b double mutants. This delay led to a transient reduction in neuromast numbers. Loss of both CD9a and CD9b sensitized embryos to reduced CXCR4b and CXCL12a levels. Together these results provide evidence that CD9 modulates collective cell migration of the pLLP through promoting CXCR4b signalling.