Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination of the Peri

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Neuron. 2008 Aug 28;59(4):581-595.

Neuregulin-1/ErbB Signaling Serves Distinct Functions in Myelination

of the Peripheral and Central Nervous System.

Brinkmann BG, Agarwal A, Sereda MW, Garratt AN, Müller T, Wende H,

Stassart RM, Nawaz S, Humml C, Velanac V, Radyushkin K, Goebbels S,

Fischer TM, lin RJ, Lai C, Ehrenreich H, Birchmeier C, Schwab

MH, Nave KA.

Department of Neurogenetics, Max Planck Institute of Experimental

Medicine, Goettingen 37075, Germany.

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.