Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination of the Peripheral and Central Nervous System

Bastian G. Brinkmann, Amit Agarwal, Michael W. Sereda, Alistair N. Garratt, Thomas Müller, Hagen Wende, Ruth M. Stassart, Schanila Nawaz, Christian Humml, Viktorija Velanac, Konstantin Radyushkin, Sandra Goebbels, Tobias M. Fischer, Robin J. Franklin, Cary Lai, Hannelore Ehrenreich, Carmen Birchmeier, Markus H. Schwab, Klaus Armin Nave

Research output: Contribution to journalArticle

Abstract

Understanding the control of myelin formation by oligodendrocytes is essential for treating demyelinating diseases. Neuregulin-1 (NRG1) type III, an EGF-like growth factor, is essential for myelination in the PNS. It is thus thought that NRG1/ErbB signaling also regulates CNS myelination, a view suggested by in vitro studies and the overexpression of dominant-negative ErbB receptors. To directly test this hypothesis, we generated a series of conditional null mutants that completely lack NRG1 beginning at different stages of neural development. Unexpectedly, these mice assemble normal amounts of myelin. In addition, double mutants lacking oligodendroglial ErbB3 and ErbB4 become myelinated in the absence of any stimulation by neuregulins. In contrast, a significant hypermyelination is achieved by transgenic overexpression of NRG1 type I or NRG1 type III. Thus, NRG1/ErbB signaling is markedly different between Schwann cells and oligodendrocytes that have evolved an NRG/ErbB-independent mechanism of myelination control.

Original languageEnglish (US)
Pages (from-to)581-595
Number of pages15
JournalNeuron
Volume59
Issue number4
DOIs
StatePublished - Aug 28 2008

Keywords

  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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    Brinkmann, B. G., Agarwal, A., Sereda, M. W., Garratt, A. N., Müller, T., Wende, H., Stassart, R. M., Nawaz, S., Humml, C., Velanac, V., Radyushkin, K., Goebbels, S., Fischer, T. M., Franklin, R. J., Lai, C., Ehrenreich, H., Birchmeier, C., Schwab, M. H., & Nave, K. A. (2008). Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination of the Peripheral and Central Nervous System. Neuron, 59(4), 581-595. https://doi.org/10.1016/j.neuron.2008.06.028