The Role of ErbB2 Signaling in the Onset of Terminal Differentiation of OligodendrocytesIn Vivo
Open Access
- 2 July 2003
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 23 (13), 5561-5571
- https://doi.org/10.1523/jneurosci.23-13-05561.2003
Abstract
The knock-out analyses of neuregulin and its receptors have indicated that they play essential roles in Schwann cell development. However, the role they play in oligodendrocyte developmentin vivohas remained unclear, because such knock-out animals die before CNS myelination begins. We examined the role of neuregulin signaling in the CNS by generating transgenic mice that express a dominant-negative mutant of the ErbB2 receptor among oligodendrocytes, using an MBP promoter. The transgenic mice exhibited widespread hypomyelination, resulting from a reduction in oligodendrocyte differentiation. The number of progenitors was conversely increased in the transgenic mice. We report that a reduction in oligodendrocyte differentiation is attributed in part to apoptosis of oligodendrocyte progenitors as they exit the cell cycle. A significant reduction in the number of p27+oligodendrocyte precursors in the transgenic mice supports this conclusion. Taken together, these data suggest that for oligodendrocyte progenitors, ErbB2 signaling plays a role in governing a properly timed exit from the cell cycle during development into myelinating oligodendrocytes.This publication has 52 references indexed in Scilit:
- Erratum: HER2/Neu: mechanisms of dimerization/oligomerizationOncogene, 2002
- Domain-specific Interactions between the p185neu and Epidermal Growth Factor Receptor Kinases Determine Differential Signaling OutcomesOnline Journal of Public Health Informatics, 1999
- Reduced Size of Retinal Ganglion Cell Axons and Hypomyelination in Mice Lacking Brain-Derived Neurotrophic FactorMolecular and Cellular Neuroscience, 1997
- ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signalingThe EMBO Journal, 1997
- Requirement for neuregulin receptor erbB2 in neural and cardiac developmentNature, 1995
- Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptorNature, 1995
- Multiple essential functions of neuregulin in developmentNature, 1995
- Does oligodendrocyte survival depend on axons?Current Biology, 1993
- Myelin basic protein gene contains separate enhancers for oligodendrocyte and Schwann cell expression.The Journal of cell biology, 1992
- Cell that are O4 antigen-positive and O1 antigen-negative differentiate into O1 antigen-positive oligodendrocytesNeuroscience Letters, 1982