CXCR4 and CXCR7 cooperate during tangential migration of facial motoneurons

Migration of facial motoneurons in the zebrafish hindbrain depends on SDF1/CXCL12 signaling. Recent studies demonstrated that SDF1 can bind two chemokine receptors, CXCR4 and CXCR7. Here we explore the expression and function of the cxcr7b gene in zebrafish hindbrain development. By the time cxcr4b-expressing motoneurons migrate from rhombomere (r) r4 to r6, expression of cxcr7b is rapidly restricted to the ventral part of r5. Inactivation of either cxcr7b or cxcr4b impairs motoneuron migration, with however different phenotypes. Facial motoneurons preferentially accumulate in r5 in cxcr7b morphant embryos, while they are distributed between r4, r5 and r6 in cxcr4b morphants. Simultaneous inactivation of both receptors leads to yet a third phenotype, with motoneurons mostly distributed between r4 and r5. The latter phenotype resembles that of sdf1a morphant embryos. Double inactivation of sdf1a and cxcr7b indeed did not lead to a complete arrest of migration but rather to a partial rescue of r5 arrest of motoneuron migration. This result is in accordance with the functional hypothesis that SDF1 might interact with CXCR7 and that they have an antagonistic effect within r5. The ectopic expression of a truncated CXCR7 receptor leads to a motoneuron migration defect. Altogether, we show that CXCR7 is required, for proper tangential migration of facial motoneurons, by determining a permissive migration pathway through r5.