Nogo-A and myelin-associated glycoprotein differently regulate oligodendrocyte maturation and myelin formation.
Nogo-A is one of the most potent oligodendrocyte-derived inhibitors for axonal regrowth in the injured adult CNS. However, the physiological function of Nogo-A in development and in healthy oligodendrocytes is still unknown. In the present study, we investigated the role of Nogo-A for myelin formation in the developing optic nerve. By quantitative real-time PCR, we found that the expression of Nogo-A increased faster in differentiating oligodendrocytes than that of the major myelin proteins MBP (myelin basic protein), PLP (proteolipid protein)/DM20, and CNP (2',3'-cyclic nucleotide 3'-phosphodiesterase). The analysis of optic nerves and cerebella of mice deficient for Nogo-A (Nogo-A(-/-)) revealed a marked delay of oligodendrocyte differentiation, myelin sheath formation, and axonal caliber growth within the first postnatal month. The combined deletion of Nogo-A and MAG caused a more severe transient hypomyelination. In contrast to MAG(-/-) mice, Nogo-A(-/-) mutants did not present abnormalities in the structure of myelin sheaths and Ranvier nodes. The common binding protein for Nogo-A and MAG, NgR1, was exclusively upregulated in MAG(-/-) animals, whereas the level of Lingo-1, a coreceptor, remained unchanged. Together, our results demonstrate that Nogo-A and MAG are differently involved in oligodendrocyte maturation in vivo, and suggest that Nogo-A may influence also remyelination in pathological conditions such as multiple sclerosis.
Pernet
Vincent
V
Department of Biology, Brain Research Institute, University of Zurich, Swiss Federal Institute of Technology, CH-8057 Zurich, Switzerland. pernet@hifo.uzh.ch
Joly
Sandrine
S
Christ
Franziska
F
Dimou
Leda
L
Schwab
Martin E
ME
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D020278:Demyelinating Autoimmune Diseases, CNS / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D018992:Myelin-Associated Glycoprotein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000166:cytology* / Q000502:physiology*; D011901:Ranvier's Nodes / Q000473:pathology
D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; C000603201:Rtn4 protein, mouse