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Science 304 (5671): 700-703

Copyright © 2004 by the American Association for the Advancement of Science

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}

Abstract: 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.

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* These authors contributed equally to this work.

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

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Type III Neuregulin-1 Is Required for Normal Sensorimotor Gating, Memory-Related Behaviors, and Corticostriatal Circuit Components.
Y.-J. J. Chen, M. A. Johnson, M. D. Lieberman, R. E. Goodchild, S. Schobel, N. Lewandowski, G. Rosoklija, R.-C. Liu, J. A. Gingrich, S. Small, et al. (2008)
J. Neurosci. 28, 6872-6883
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Endurance and Resistance Exercise Training Programs Elicit Specific Effects on Sciatic Nerve Regeneration After Experimental Traumatic Lesion in Rats.
J. Ilha, R. T. Araujo, T. Malysz, E. E. S. Hermel, P. Rigon, L. L. Xavier, and M. Achaval (2008)
Neurorehabil Neural Repair 22, 355-366
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From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases.
M. Dubois-Dalcq, A. Williams, C. Stadelmann, B. Stankoff, B. Zalc, and C. Lubetzki (2008)
Brain 131, 1686-1700
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Gene-regulation logic in retinal ganglion cell development: Isl1 defines a critical branch distinct from but overlapping with Pou4f2.
X. Mu, X. Fu, P. D. Beremand, T. L. Thomas, and W. H. Klein (2008)
PNAS 105, 6942-6947
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Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice.
A. V. Savonenko, T. Melnikova, F. M. Laird, K.-A. Stewart, D. L. Price, and P. C. Wong (2008)
PNAS 105, 5585-5590
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Protein Kinase A-Induced Phosphorylation of the p65 Subunit of Nuclear Factor-{kappa}B Promotes Schwann Cell Differentiation into a Myelinating Phenotype.
C. Yoon, Z. Korade, and B. D. Carter (2008)
J. Neurosci. 28, 3738-3746
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The Mitochondrial Protease AFG3L2 Is Essential for Axonal Development.
F. Maltecca, A. Aghaie, D. G. Schroeder, L. Cassina, B. A. Taylor, S. J. Phillips, M. Malaguti, S. Previtali, J.-L. Guenet, A. Quattrini, et al. (2008)
J. Neurosci. 28, 2827-2836
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Transcriptional Control of Cholesterol Biosynthesis in Schwann Cells by Axonal Neuregulin 1.
M. Pertusa, C. Morenilla-Palao, C. Carteron, F. Viana, and H. Cabedo (2007)
J. Biol. Chem. 282, 28768-28778
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Axonal Neurofilaments Control Multiple Fiber Properties But Do Not Influence Structure or Spacing of Nodes of Ranvier.
R. Perrot, P. Lonchampt, A. C. Peterson, and J. Eyer (2007)
J. Neurosci. 27, 9573-9584
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Putting the glue in glia: Necls mediate Schwann cell axon adhesion.
J. R. Perlin and W. S. Talbot (2007)
J. Cell Biol. 178, 721-723
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Nectin-like proteins mediate axon Schwann cell interactions along the internode and are essential for myelination.
P. Maurel, S. Einheber, J. Galinska, P. Thaker, I. Lam, M. B. Rubin, S. S. Scherer, Y. Murakami, D. H. Gutmann, and J. L. Salzer (2007)
J. Cell Biol. 178, 861-874
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