TY - JOUR
T1 - Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination of the Peripheral and Central Nervous System
AU - Brinkmann, Bastian G.
AU - Agarwal, Amit
AU - Sereda, Michael W.
AU - Garratt, Alistair N.
AU - Müller, Thomas
AU - Wende, Hagen
AU - Stassart, Ruth M.
AU - Nawaz, Schanila
AU - Humml, Christian
AU - Velanac, Viktorija
AU - Radyushkin, Konstantin
AU - Goebbels, Sandra
AU - Fischer, Tobias M.
AU - Franklin, Robin J.
AU - Lai, Cary
AU - Ehrenreich, Hannelore
AU - Birchmeier, Carmen
AU - Schwab, Markus H.
AU - Nave, Klaus Armin
N1 - Funding Information:
We thank A. Fahrenholz and P. Soban for help with histology; G. Fricke-Bode for cell culture work; W. Möbius, T. Ruhwedel, and C. Griffel for help with electron microscopy; and I. Bormuth for brain sections of NEXCre ∗ floxtau-GFP-lacZ mice. We thank S. Emme, M. Schindler, and S. Thiel (MPI, Göttingen) for generating transgenic mice; E. Rhode (MDC Berlin) for help with ES cell culture; P. Stallerow and C. Päseler (MDC Berlin) for help with animal husbandry; and B. Jerchow and K. Becker for blastocyst injections. We also thank M. Gassman for providing ErbB4 mutants; R. Klein for CamKII-Cre mice; G. Schütz for Nestin-Cre mice; K. Jones for Emx-Cre mice; and S. Arber for floxtau-GFP-lacZ mice. We acknowledge C. Stiles for Olig2 antibody; M. Less for PLP antibody 3F4; D. Meijer for Krox20 antibody; J.J. Archelos for MPZ antibody; and J. Salzer, M. Simons, and members of the Nave lab for helpful discussions. K.-A.N. acknowledges grant support from the Deutsche Forschungsgemeinschaft (CMPB), the National Multiple Sclerosis Society, the Hertie Institute of MS Research, the Myelin Project, and the BMBF. C.B., T.M., A.N.G., and H.W. are supported by grants from the Deutsche Forschungsgemeinschaft (SFB 665) and the BMBF. C.L. is supported by the National Institutes of Health (NS32367). We dedicate this paper to the memory of C.H., who tragically died.
PY - 2008/8/28
Y1 - 2008/8/28
N2 - 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.
AB - 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.
KW - DEVBIO
KW - MOLNEURO
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U2 - 10.1016/j.neuron.2008.06.028
DO - 10.1016/j.neuron.2008.06.028
M3 - Article
C2 - 18760695
AN - SCOPUS:49849089713
SN - 0896-6273
VL - 59
SP - 581
EP - 595
JO - Neuron
JF - Neuron
IS - 4
ER -