Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system |
| |
Authors: | Brinkmann Bastian G Agarwal Amit Sereda Michael W Garratt Alistair N Müller Thomas Wende Hagen Stassart Ruth M Nawaz Schanila Humml Christian Velanac Viktorija Radyushkin Konstantin Goebbels Sandra Fischer Tobias M Franklin Robin J Lai Cary Ehrenreich Hannelore Birchmeier Carmen Schwab Markus H Nave Klaus Armin |
| |
Institution: | Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen 37075, Germany. |
| |
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: | |
本文献已被 PubMed 等数据库收录! |
|