Hermes regulates axon sorting in the optic tract by post-transcriptional regulation of Neuropilin 1

The establishment of precise topographic maps during neural development is facilitated by the pre-sorting of axons in the pathway before they reach their targets. In the vertebrate visual system such topography is clearly seen in the optic tract and in the optic radiations. However, the molecular mechanisms involved in pre-target axon sorting are poorly understood. Here we show that in zebrafish the RNA-binding protein, Hermes, which is expressed exclusively in retinal ganglion cells (RGCs), is involved in this process. Using a RiboTag approach, we show that Hermes acts as a negative translational regulator of specific mRNAs in RGCs. One of these targets is the guidance cue receptor Neuropilin 1 (Nrp1) which is sensitive to the repellent cue Semaphorin 3A (Sema3A). Hermes knockdown leads to topographic missorting in the optic tract through the up-regulation of Nrp1. Restoring Nrp1 to appropriate levels in Hermes-depleted embryos rescues this effect and corrects the axon sorting defect in the optic tract. Our data indicate that axon sorting relies on Hermes-regulated translation of Nrp1.