Chemokine turnover keeps neurons on track

Changes in a chemoattractant’s expression pattern help guide migrating neurons to the right embryonic location, Lewellis et al. reveal.

During zebrafish development, trigeminal sensory neurons (TgSNs) are attracted to a posterior ganglion assembly site by the chemokine SDF1a, which activates a G protein–coupled receptor called Cxcr4b on the neurons. SDF1a is also produced in other parts of the embryonic head, yet TgSNs aren’t attracted to these alternative sources of the chemokine.

To find out why, Lewellis et al. examined SDF1a’s expression pattern in more detail and found that its mRNA was initially produced in a stripe of cells stretching from the ganglion assembly site to the TgSNs’ birthplace. SDF1a expression was then shut off in more anterior cells as the migrating neurons passed them by en route to their destination.

The researchers discovered that a microRNA, miR-430, was responsible for down-regulating SDF1a mRNA, while a noncanonical chemokine receptor, Cxcr7b, was expressed by nonneuronal cells to scavenge any remaining SDF1a protein. Inhibiting the function of miR-430 or Cxcr7b caused SDF1a levels to persist, resulting in the mislocalization of TgSNs, some of which migrated away from the ganglion assembly site and toward other sources of SDF1a instead.

Lewellis et al. think that, by dynamically refining SDF1a’s expression, zebrafish embryos maintain a relatively high concentration of the chemokine on the posterior side of TgSNs, reeling in the neurons to the ganglion assembly site so that they ignore alternative SDF1a sources. The authors now plan to investigate why TgSNs migrate in clusters instead of as individual cells.