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Publication : Netrin-1 acts as a repulsive guidance cue for sensory axonal projections toward the spinal cord.

First Author  Masuda T Year  2008
Journal  J Neurosci Volume  28
Issue  41 Pages  10380-5
PubMed ID  18842897 Mgi Jnum  J:141124
Mgi Id  MGI:3815395 Doi  10.1523/JNEUROSCI.1926-08.2008
Citation  Masuda T, et al. (2008) Netrin-1 acts as a repulsive guidance cue for sensory axonal projections toward the spinal cord. J Neurosci 28(41):10380-5
abstractText  During early development, the ventral spinal cord expresses chemorepulsive signals that act on dorsal root ganglion (DRG) axons to help orient them toward the dorsolateral part of the spinal cord. However, the molecular nature of this chemorepulsion is mostly unknown. We report here that netrin-1 acts as an early ventral spinal cord-derived chemorepellent for DRG axons. In the developing mouse spinal cord, netrin-1 is expressed in the floor plate of the spinal cord, and the netrin receptor Unc5c is expressed in DRG neurons. We show that human embryonic kidney cell aggregates secreting netrin-1 repel DRG axons and that netrin-1-deficient ventral spinal cord explants lose their repulsive influence on DRG axons. In embryonic day 10 netrin-1 mutant mice, we find that DRG axons exhibit transient misorientation. Furthermore, by means of gain-of-function analyses, we show that ectopic netrin-1 in the dorsal and intermediate spinal cord prevents DRG axons from being directed toward the dorsal spinal cord. Together, these findings suggest that netrin-1 contributes to the formation of the initial trajectories of developing DRG axons as a repulsive guidance cue.
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