Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination

Martha Zeger, Greg Popken, Jihui Zhang, Shouhong Xuan, Q. Richard Lu, Markus H. Schwab, Klaus Armin Nave, David Rowitch, A. Joseph D'Ercole, Ping Ye

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Insulin-like growth factor-I (IGF-I) has been shown to be a potent agent in promoting the growth and differentiation of oligodendrocyte precursors, and in stimulating myelination during development and following injury. To definitively determine whether IGF-I acts directly on the cells of oligodendrocyte lineage, we generated lines of mice in which the type 1 IGF receptor gene (igf1r) was conditionally ablated either in Olig1 or proteolipid protein expressing cells (termed IGF1Rpre-oligo-ko and IGF1Roligo-ko mice, respectively). Compared with wild type mice, IGF1Rpre-oligo-ko mice had a decreased volume (by 35-55%) and cell number (by 54-70%) in the corpus callosum (CC) and anterior commissure at 2 and 6 weeks of age, respectively. IGF1Roligo-ko mice by 25 weeks of age also showed reductions, albeit less marked, in CC volume and cell number. Unlike astrocytes, the percentage of NG2+ oligodendrocyte precursors was decreased by ∼13% in 2-week-old IGF1Rpre-oligo-ko mice, while the percentage of CC1 + mature oligodendrocytes was decreased by ∼24% in 6-week-old IGF1Rpre-oligo-ko mice and ∼25% in 25-week-old IGF1R oligo-ko mice. The reduction in these cells is apparently a result of decreased proliferation and increased apoptosis. These results indicate that IGF-I directly affects oligodendrocytes and myelination in vivo via IGF1R, and that IGF1R signaling in the cells of oligodendroeyte lineage is required for normal oligodendrocyte development and myelination. These data also provide a fundamental basis for developing strategies with the potential to target IGF-IGF1R signaling pathways in oligodendrocyte lineage cells for the treatment of demyelinating disorders.

Original languageEnglish (US)
Pages (from-to)400-411
Number of pages12
JournalGLIA
Volume55
Issue number4
DOIs
StatePublished - Mar 2007

Keywords

  • IGF-I
  • IGF1R
  • MBP
  • Mutant mice
  • Olig1
  • Oligodendrocyte precursors
  • PLP

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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    Zeger, M., Popken, G., Zhang, J., Xuan, S., Lu, Q. R., Schwab, M. H., Nave, K. A., Rowitch, D., D'Ercole, A. J., & Ye, P. (2007). Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination. GLIA, 55(4), 400-411. https://doi.org/10.1002/glia.20469