The ErbB4 neuregulin receptor mediates suppression of oligodendrocyte maturation

Caroline R. Sussman, Timothy Vartanian, Robert H. Miller

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Neuregulin is required for proper oligodendrocyte development, but which receptors are involved and whether neuregulin promotes or inhibits maturation remain controversial. To assess the roles of the neuregulin receptor ErbB4 in oligodendrocyte development, we examined oligodendrocyte initiation and maturation in cultures derived from erbB4 knock-out mice and rat spinal cord in the presence of neutralizing erbB4 antibodies. No differences in the development of O4+ oligodendrocytes were detected in the presence or absence of erbB4 signaling. All four epidermal growth factor receptor family members were detected in the ventral neural tube at approximately the time of initial oligodendrocyte development, consistent with redundancy in neuregulin receptor signaling at the onset of oligodendrocyte development. In contrast, greater numbers of differentiated (monoclonal antibody O1+) oligodendrocytes developed in neural tube explants from erbB4-/- mice than either erbB4+/+ or erbB4+/- littermates as well as in cultures treated with anti-erbB4. These data indicate that ErbB4 is not required for oligodendrocyte development and, in fact, inhibits oligodendrocyte lineage maturation. Together with previous studies, these data suggest a model in which early oligodendrocyte lineage development is regulated by promiscuous neuregulin receptor signaling, but subsequent lineage progression occurs through a balance of receptor-specific promotion or inhibition of maturation.

Original languageEnglish (US)
Pages (from-to)5757-5762
Number of pages6
JournalJournal of Neuroscience
Volume25
Issue number24
DOIs
StatePublished - Jun 15 2005

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Keywords

  • CNS
  • Differentiation
  • Embryo
  • Growth factor
  • Immunohistochemistry
  • Knock-out
  • Neural tube
  • Neuregulin
  • Oligodendrocyte
  • Receptor
  • Spinal cord
  • erbB4

ASJC Scopus subject areas

  • Neuroscience(all)

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