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PMID: 8509457 Published · ppublish English Journal Article

A role for TGF-beta in oligodendrocyte differentiation.

The Journal of cell biology ·Vol. 121 ·No. 6 ·1993-06-00 ·Pages 1397-407

McKinnon RD, Piras G, Ida JA, Dubois-Dalcq M

Abstract

Oligodendrocyte-type-2 astrocyte (O-2A) glial progenitor cells undergo a limited number of mitotic divisions in response to PDGF before differentiating into oligodendrocytes, the myelin-forming cell of the CNS. We examined the mechanism limiting O-2A proliferation, and demonstrate that these cells secrete an inhibitor of cell proliferation that can be neutralized with antibodies to TGF-beta. O-2A cells also secrete an inhibitory activity that cannot be neutralized with TGF-beta antibodies. O-2A progenitor cultures express TGF-beta 1 isoform and its transcript, while oligodendrocyte cultures express TGF-beta 1, beta-2, and beta-3 isoforms. Both recombinant TGF-beta 1 and O-2A conditioned medium inhibit the proliferation of O-2A progenitor cells cultured in the presence of PDGF, and this inhibition can be partially neutralized with polyclonal TGF-beta antibodies. Thus, TGF-beta produced by O-2A cells may limit PDGF-driven mitosis and promote oligodendrocyte development. TGF-beta is a less potent inhibitor of O-2A proliferation when these cells are cultured in the presence of bFGF, suggesting that bFGF interferes with TGF-beta signaling. Thus, the production of TGF-beta by cells in the O-2A lineage may account for the distinct effects of PDGF and bFGF on O-2A progenitor cell proliferation. Moreover, our results suggest that TGF-beta may be an important mediator of oligodendrocyte differentiation.

MeSH Terms
Amino Acid Sequence Animals Antibodies Base Sequence Cell Differentiation/physiology Cell Division Cells, Cultured Immunohistochemistry Molecular Sequence Data Oligodendroglia/cytology RNA, Messenger/metabolism Rats Rats, Sprague-Dawley Transforming Growth Factor beta/immunology,metabolism,physiology
Chemicals
Antibodies RNA, Messenger Transforming Growth Factor beta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
McKinnon R D
Division of Neurosurgery, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.
Piras G
Ida J A
Dubois-Dalcq M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1993-06-00
Pages
1397-407
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119703
Subset
IM
Databases
GENBANK
X71903, X71904
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