Nogo-A expressed in Schwann cells impairs axonal regeneration after peripheral nerve injury.
Injured axons in mammalian peripheral nerves often regenerate successfully over long distances, in contrast to axons in the brain and spinal cord (CNS). Neurite growth-inhibitory proteins, including the recently cloned membrane protein Nogo-A, are enriched in the CNS, in particular in myelin. Nogo-A is not detectable in peripheral nerve myelin. Using regulated transgenic expression of Nogo-A in peripheral nerve Schwann cells, we show that axonal regeneration and functional recovery are impaired after a sciatic nerve crush. Nogo-A thus overrides the growth-permissive and -promoting effects of the lesioned peripheral nerve, demonstrating its in vivo potency as an inhibitor of axonal regeneration.
Pot
Caroline
C
Brain Research Institute, University of Zurich, and Department of Biology, Swiss Federal Institute of Technology Zurich, CH-8057 Zurich, Switzerland. caroline.pot@access.unizh.ch
Simonen
Marjo
M
Weinmann
Oliver
O
Schnell
Lisa
L
Christ
Franziska
F
Stoeckle
Sascha
S
Berger
Philipp
P
Rülicke
Thomas
T
Suter
Ueli
U
Schwab
Martin E
ME
D000818:Animals; D001369:Axons / Q000502:physiology*; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000502:physiology*; D000070798:Nogo Proteins; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries / Q000502:physiology* / Q000648:ultrastructure; D019076:Transgenes
D019922:GAP-43 Protein; D006131:Growth Inhibitors; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat