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