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Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system

Item Type:Article
Title:Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system
Creators Name:Brinkmann, B.G. and Agarwal, A. and Sereda, M.W. and Garratt, A.N. and Mueller, T. and Wende, H. and Stassart, R.M. and Nawaz, S. and Humml, C. and Velanac, V. and Radyushkin, K. and Goebbels, S. and Fischer, T.M. and Franklin, R.J. and Lai, C. and Ehrenreich, H. and Birchmeier, C. and Schwab, M.H. and Nave, K.A.
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.
Keywords:MOLNEURO, DEVBIO, Animals, Mice
Publisher:Cell Press (U.S.A.)
Page Range:581-595
Date:28 August 2008
Official Publication:https://doi.org/10.1016/j.neuron.2008.06.028
PubMed:View item in PubMed

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