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A role for TGF-beta in oligodendrocyte differentiation
R D McKinnon1, G Piras, J A Ida
1Division of Neurosurgery, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.
The Journal of Cell Biology
|June 1, 1993
Summary
Oligodendrocyte progenitor cells secrete a TGF-beta inhibitor that limits their proliferation. This finding suggests TGF-beta (transforming growth factor-beta) is key to oligodendrocyte development and CNS myelin formation.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Oligodendrocyte-type-2 astrocyte (O-2A) glial progenitor cells proliferate in response to PDGF.
- Proliferation is limited before differentiation into oligodendrocytes, the CNS myelin-forming cells.
Purpose of the Study:
- To investigate the mechanism limiting O-2A progenitor cell proliferation.
- To determine the role of TGF-beta in O-2A cell proliferation and oligodendrocyte differentiation.
Main Methods:
- Cultured O-2A progenitor cells and oligodendrocytes.
- Assessed cell proliferation in response to PDGF and bFGF.
- Analyzed TGF-beta isoform expression (TGF-beta 1, beta-2, beta-3).
- Utilized recombinant TGF-beta 1 and O-2A conditioned medium.
- Employed TGF-beta neutralizing antibodies.
Main Results:
- O-2A cells secrete a TGF-beta-neutralizable inhibitor of proliferation.
- O-2A cells also produce an uncharacterized inhibitory activity.
- TGF-beta 1 is expressed in progenitor cells; TGF-beta 1, beta-2, and beta-3 in oligodendrocytes.
- Recombinant TGF-beta 1 and O-2A conditioned medium inhibit PDGF-driven proliferation.
- bFGF reduces TGF-beta's inhibitory effect, suggesting interference with TGF-beta signaling.
Conclusions:
- TGF-beta produced by O-2A lineage cells likely limits PDGF-stimulated mitosis.
- TGF-beta may promote oligodendrocyte differentiation and CNS myelin formation.
- Distinct signaling pathways of PDGF and bFGF involve TGF-beta.