Stage-specific effects of bone morphogenetic proteins on the oligodendrocyte lineage

Judith Grinspan, Eric Edell, David F. Carpio, Jacqueline S. Beesley, LeaAnn Lavy, David E Pleasure, Jeffrey A. Golden

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Oligodendrocyte maturation is regulated by multiple secreted factors present in the brain during critical stages of development. Whereas most of these factors promote oligodendrocyte proliferation and survival, members of the bone morphogenetic protein family (BMPs) recently have been shown to inhibit oligodendrocyte differentiation in vitro. Oligodendrocyte precursors treated with BMPs differentiate to the astrocyte lineage. Given that cells at various stages of the oligodendrocyte lineage have distinct responses to growth factors, we hypothesized that the response to BMP would be stage- specific. Using highly purified, stage-specific cultures, we found that BMP has distinct effects on cultured oligodendrocyte preprogenitors, precursors, and mature oligodendrocytes. Oligodendrocyte preprogenitors (PSA-NCAM+, A2B5- ) treated with BMP2 or BMP4 developed a novel astrocyte phenotype characterized by a morphological change and expression of glial fibrillary acidic protein (GFAP) but little glutamine synthetase expression and no labeling with A2B5 antibody. In contrast, treating oligodendrocyte precursors with BMPs resulted in the accumulation of cells with the traditional type 2 astrocyte phenotype (GFAP+, A2B5+). However, many of the cells with an astrocytic morphology did not express GFAP or glutamine synthetase unless thyroid hormone was present in the medium. The addition of fibroblast growth factor along with BMP to either oligodendrocyte preprogenitor or the oligodendrocyte precursor cells inhibited the switch to the astrocyte lineage, whereas platelet-derived growth factor addition had no effect. Treatment of mature oligodendrocytes with BMP elicited no change in morphology or expression of GFAP. These data suggest that as cells progress through the oligodendrocyte lineage, they show developmentally restricted responses to the BMPs.

Original languageEnglish (US)
Pages (from-to)1-17
Number of pages17
JournalJournal of Neurobiology
Volume43
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Bone Morphogenetic Proteins
Oligodendroglia
Glial Fibrillary Acidic Protein
Astrocytes
Glutamate-Ammonia Ligase
Phenotype
Fibroblast Growth Factors
Platelet-Derived Growth Factor
Thyroid Hormones
Intercellular Signaling Peptides and Proteins

Keywords

  • Bone morphogenetic protein
  • Glial fibrillary acidic protein
  • Glutamine synthetase
  • Oligodendrocytes
  • Thyroid hormone

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Stage-specific effects of bone morphogenetic proteins on the oligodendrocyte lineage. / Grinspan, Judith; Edell, Eric; Carpio, David F.; Beesley, Jacqueline S.; Lavy, LeaAnn; Pleasure, David E; Golden, Jeffrey A.

In: Journal of Neurobiology, Vol. 43, No. 1, 2000, p. 1-17.

Research output: Contribution to journalArticle

Grinspan, Judith ; Edell, Eric ; Carpio, David F. ; Beesley, Jacqueline S. ; Lavy, LeaAnn ; Pleasure, David E ; Golden, Jeffrey A. / Stage-specific effects of bone morphogenetic proteins on the oligodendrocyte lineage. In: Journal of Neurobiology. 2000 ; Vol. 43, No. 1. pp. 1-17.
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