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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.

Pubmed ID: 18760695

Authors

  • 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
  • Franklin RJ
  • Lai C
  • Ehrenreich H
  • Birchmeier C
  • Schwab MH
  • Nave KA

Journal

Neuron

Publication Data

August 28, 2008

Associated Grants

  • Agency: Medical Research Council, Id: G0701476
  • Agency: NINDS NIH HHS, Id: NS32367
  • Agency: NIMH NIH HHS, Id: R21 MH073127-01

Mesh Terms

  • Animals
  • Central Nervous System
  • Gene Dosage
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Nerve Fibers, Myelinated
  • Neuregulin-1
  • Neurons
  • Oligodendroglia
  • Peripheral Nervous System
  • Receptor, Epidermal Growth Factor
  • Receptor, ErbB-3
  • Receptor, ErbB-4
  • Schwann Cells
  • Signal Transduction