Neuregulin-1/ErbB signaling serves distinct functions in myelination of the peripheral and central nervous system.
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.
Brinkmann
Bastian G
BG
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen 37075, Germany.
Agarwal
Amit
A
Sereda
Michael W
MW
Garratt
Alistair N
AN
Müller
Thomas
T
Wende
Hagen
H
Stassart
Ruth M
RM
Nawaz
Schanila
S
Humml
Christian
C
Velanac
Viktorija
V
Radyushkin
Konstantin
K
Goebbels
Sandra
S
Fischer
Tobias M
TM
Franklin
Robin J
RJ
Lai
Cary
C
Ehrenreich
Hannelore
H
Birchmeier
Carmen
C
Schwab
Markus H
MH
Nave
Klaus Armin
KA