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

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Item Type:Article
Title:Hermes regulates axon sorting in the optic tract by post-trancriptional regulation of Neuropilin 1
Creators Name:Hörnberg, H. and Cioni, J.M. and Harris, W.A. and Holt, C.E.
Abstract:The establishment of precise topographic maps during neural development is facilitated by the presorting of axons in the pathway before they reach their targets. In the vertebrate visual system, such topography is seen clearly in the optic tract (OT) and in the optic radiations. However, the molecular mechanisms involved in pretarget axon sorting are poorly understood. Here, we show in zebrafish that 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 knock-down leads to topographic missorting in the OT through the upregulation of Nrp1. Restoring Nrp1 to appropriate levels in Hermes-depleted embryos rescues this effect and corrects the axon-sorting defect in the OT. Our data indicate that axon sorting relies on Hermes-regulated translation of Nrp1. SIGNIFICANCE STATEMENT: An important mechanism governing the formation of the mature neural map is pretarget 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 knock-down resulting in aberrant growth cone cue sensitivity and axonal topographic misprojections. We characterize a novel RNA-based mechanism by which axons restrict their translatome developmentally to achieve proper targeting.
Keywords:Axon Sorting, RNA-Binding Protein, Topography, Visual System, Animals, Xenopus laevis, Zebrafish
Source:Journal of Neuroscience
Publisher:Society for Neuroscience
Page Range:12697-12706
Date:14 December 2016
Official Publication:https://doi.org/10.1523/JNEUROSCI.2400-16.2016
PubMed:View item in PubMed

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