RT Journal Article
SR Electronic
T1 Hermes regulates axon sorting in the optic tract by post-transcriptional regulation of Neuropilin 1
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2400-16
DO 10.1523/JNEUROSCI.2400-16.2016
A1 Hanna Hörnberg
A1 Jean-Michel Cioni
A1 William A. Harris
A1 Christine E. Holt
YR 2016
UL http://www.jneurosci.org/content/early/2016/11/09/JNEUROSCI.2400-16.2016.abstract
AB 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.SIGNIFICANCE STATEMENTAn important mechanism governing the formation of the mature neural map is pre-target axon sorting within the sensory tract, however the molecular mechanisms involved in this process remain largely unknown. The work presented here reveals a novel function for the RNA-binding protein Hermes, in regulating the topographic sorting of retinal ganglion cell (RGC) axons in the optic tract and tectum. We find that Hermes negatively controls the translation of the guidance-cue receptor Neuropilin-1 in RGCs, with Hermes knockdown resulting in aberrant growth cone cue-sensitivity and axonal topographic misprojections. We characterize a novel RNA-based mechanism by which axons developmentally restrict their translatome in order to achieve proper targeting.