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The Journal of Neuroscience, July 16, 2008, 28(29):7435-7444; doi:10.1523/JNEUROSCI.0727-08.2008

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Development/Plasticity/Repair
Nogo-A and Myelin-Associated Glycoprotein Differently Regulate Oligodendrocyte Maturation and Myelin Formation

Vincent Pernet,¹ Sandrine Joly,² Franziska Christ,¹ Leda Dimou,¹ and Martin E. Schwab¹

¹Brain Research Institute, University of Zurich, and Department of Biology, Swiss Federal Institute of Technology, CH-8057 Zurich, Switzerland, and ²Laboratory for Retinal Cell Biology, Department of Ophthalmology, University of Zurich, CH-8091 Zurich, Switzerland

Correspondence should be addressed to Dr. Vincent Pernet, Brain Research Institute, University of Zurich/Swiss Federal Institute of Technology, Winterthurerstrasse 190, Room 55J34a, CH-8057 Zurich, Switzerland. Email: pernet{at}hifo.uzh.ch

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.

Key words: Nogo-A; oligodendrocyte; myelination; OPC; optic nerve; cerebellum

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Received Feb. 16, 2008; revised May 15, 2008; accepted June 9, 2008.

Correspondence should be addressed to Dr. Vincent Pernet, Brain Research Institute, University of Zurich/Swiss Federal Institute of Technology, Winterthurerstrasse 190, Room 55J34a, CH-8057 Zurich, Switzerland. Email: pernet{at}hifo.uzh.ch

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