Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination of the Peripheral and Central Nervous System
| Autor: | Christian Humml, Thomas Müller, Viktorija Velanac, Schanila Nawaz, Markus H. Schwab, Hannelore Ehrenreich, Michael W. Sereda, Sandra Goebbels, Bastian G. Brinkmann, Hagen Wende, Konstantin Radyushkin, Ruth M. Stassart, Cary Lai, Robin J.M. Franklin, Klaus-Armin Nave, Tobias M. Fischer, Alistair N. Garratt, Amit Agarwal, Carmen Birchmeier |
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| Rok vydání: | 2008 |
| Předmět: |
Central Nervous System
Receptor ErbB-4 Receptor ErbB-3 Neuroscience(all) Neuregulin-1 Gene Dosage DEVBIO Nerve Fibers Myelinated MOLNEURO Article Mice 03 medical and health sciences Myelin ErbB Receptors 0302 clinical medicine ErbB Peripheral Nervous System mental disorders medicine Animals Neuregulin 1 ERBB4 030304 developmental biology Mice Knockout Neurons 0303 health sciences biology General Neuroscience Gene Expression Regulation Developmental Mice Mutant Strains Oligodendroglia medicine.anatomical_structure nervous system biology.protein Neuregulin Schwann Cells Signal transduction Neuroscience Neural development 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neuron; Vol 59 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2008.06.028 |
| Popis: | SummaryUnderstanding 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. |
| Databáze: | OpenAIRE |
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