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Originally published in Science Express on 25 March 2004
Science 30 April 2004:
Vol. 304. no. 5671, pp. 700 - 703
DOI: 10.1126/science.1095862
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Research Articles

Axonal Neuregulin-1 Regulates Myelin Sheath Thickness

Galin V. Michailov,1* Michael W. Sereda,1,2* Bastian G. Brinkmann,1 Tobias M. Fischer,4 Bernhard Haug,3 Carmen Birchmeier,5 Lorna Role,6 Cary Lai,4 Markus H. Schwab,1 Klaus-Armin Nave1,7{dagger}

In the nervous system of vertebrates, myelination is essential for rapid and accurate impulse conduction. Myelin thickness depends on axon fiber size. We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells. Reduced Nrg1 expression causes hypomyelination and reduced nerve conduction velocity. Neuronal overexpression of Nrg1 induces hypermyelination and demonstrates that Nrg1 type III is the responsible isoform. We suggest a model by which myelin-forming Schwann cells integrate axonal Nrg1 signals as a biochemical measure of axon size.

1 Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
2 Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.
3 Department of Clinical Neurophysiology, University of Göttingen, 37075 Göttingen, Germany.
4 Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
5 Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
6 Columbia University, New York, NY 10032, USA.
7 Hertie Institute of Multiple Sclerosis Research, 37075 Göttingen, Germany.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: nave{at}em.mpg.de

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