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Dorsally derived netrin 1 provides an inhibitory cue and elaborates the`waiting period' for primary sensory axons in the developing spinal cord

Authors: Keisuke Watanabe; Susan L. Ackerman; Katsuhiko Ono; Katsuhiko Ono; Kazuhiro Ikenaka; Kazuhiro Ikenaka; Takahiro Furuta; +2 Authors

Dorsally derived netrin 1 provides an inhibitory cue and elaborates the`waiting period' for primary sensory axons in the developing spinal cord

Abstract

Dorsal root ganglion (DRG) neurons extend axons to specific targets in the gray matter of the spinal cord. During development, DRG axons grow into the dorsolateral margin of the spinal cord and projection into the dorsal mantle layer occurs after a `waiting period' of a few days. Netrin 1 is a long-range diffusible factor expressed in the ventral midline of the developing neural tube, and has chemoattractive and chemorepulsive effects on growing axons. Netrin 1 is also expressed in the dorsal spinal cord. However, the roles of dorsally derived netrin 1 remain totally unknown. Here, we show that dorsal netrin 1 controls the correct guidance of primary sensory axons. During the waiting period, netrin 1 is transiently expressed or upregulated in the dorsal spinal cord, and the absence of netrin 1 results in the aberrant projection of sensory axons, including both cutaneous and proprioceptive afferents, into the dorsal mantle layer. Netrin 1 derived from the dorsal spinal cord, but not the floor plate, is involved in the correct projection of DRG axons. Furthermore,netrin 1 suppresses axon outgrowth from DRG in vitro. Unc5crcm mutant shows abnormal invasion of DRG axons as observed in netrin 1 mutants. These results are the first direct evidence that netrin 1 in the dorsal spinal cord acts as an inhibitory cue for primary sensory axons and is a crucial signal for the formation of sensory afferent neural networks.

Keywords

570, Mice, Inbred ICR, Indoles, Epidermal Growth Factor, 610, Galactosides, Netrin-1, Immunohistochemistry, Models, Biological, Axons, Cell Line, Mice, Organ Culture Techniques, Pregnancy, Cricetinae, Ganglia, Spinal, Mutation, Animals, Female, Nerve Growth Factors, Neurons, Afferent, In Situ Hybridization

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    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
75
Top 10%
Top 10%
Top 10%
bronze