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

被引：298

作者：

Brinkmann, Bastian G. ^{[1
]}

Agarwal, Amit ^{[1
]}

Sereda, Michael W. ^{[1
,2
,3
]}

Garratt, Alistair N. ^{[4
]}

Mueller, Thomas ^{[4
]}

Wende, Hagen ^{[4
]}

Stassart, Ruth M. ^{[1
]}

Nawaz, Schanila ^{[1
]}

Humml, Christian ^{[1
]}

Velanac, Viktorija ^{[1
]}

Radyushkin, Konstantin ^{[5
]}

Goebbels, Sandra ^{[1
]}

Fischer, Tobias M. ^{[1
]}

Franklin, Robin J. ^{[6
]}

Lai, Cary ^{[7
]}

Ehrenreich, Hannelore ^{[5
]}

Birchmeier, Carmen ^{[4
]}

Schwab, Markus H. ^{[1
]}

Nave, Klaus Armin ^{[1
,8
]}

机构：

[1] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany

[2] Univ Gottingen, Dept Neurol, D-37075 Gottingen, Germany

[3] Univ Gottingen, Dept Clin Neurophysiol, D-37075 Gottingen, Germany

[4] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

[5] Max Planck Inst Expt Med, Div Clin Neurosci, D-37075 Gottingen, Germany

[6] Univ Cambridge, Dept Vet Med, Cambridge Ctr Brain Repair, Cambridge CB3 0ES, England

[7] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA

[8] Hertie Inst Multiple Sclerosis Res, D-37073 Gottingen, Germany

来源：

NEURON | 2008年 / 59卷 / 04期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1016/j.neuron.2008.06.028

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 oligo-dendroglial 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.

引用

页码：581 / 595

页数：15

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