Netrin-1 is a novel myelin-associated inhibitor to axon growth.
We investigated the influence of the bifunctional guidance molecule netrin-1 on axonal growth in the injured adult spinal cord. In the adult, netrin-1 is expressed on mature oligodendrocytes, cells of the central canal, and the meninges. Netrin-1 protein in white matter is selectively enriched adjacent to paranodal loops of myelin in nodes of Ranvier. The repulsion-mediating netrin-1 uncoordinated-5 (UNC5) receptors are expressed by neurons of the corticospinal and rubrospinal projections, and by intrinsic neurons of the spinal cord, both before and after spinal cord injury. Neutralization of netrin-1 in myelin prepared from adult rat spinal cord using UNC5 receptor bodies increases neurite outgrowth from UNC5-expressing spinal motor neurons in vitro. Furthermore, axon regeneration is inhibited in a netrin-1-enriched zone, devoid of other myelin-associated inhibitors, within spinal cord lesion sites in vivo. We conclude that netrin-1 is a novel oligodendrocyte-associated inhibitor that can contribute to axonal growth failure after adult spinal cord injury.
Löw
Karin
K
Department of Neurosciences, University of California-San Diego, La Jolla, California 92093, USA. kloew@ucsd.edu
Culbertson
Maya
M
Bradke
Frank
F
Tessier-Lavigne
Marc
M
Tuszynski
Mark H
MH
D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology*; D049109:Cell Proliferation; D005260:Female; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000075388:Netrin-1; D009836:Oligodendroglia / Q000473:pathology / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D006131:Growth Inhibitors; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1