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GGF/neuregulin induces a phenotypic reversion of oligodendrocytes
P D Canoll1, R Kraemer, K K Teng
1Department of Pharmacology, New York University Medical School, 550 First Avenue, New York, New York 10016, USA.
Abstract:
We have previously shown that glial growth factor (GGF), a member of the neuregulin (NRG) family of growth factors, is a mitogen and survival factor for oligodendrocyte progenitors in cell culture and blocks their differentiation at the pro-oligodendrocyte stage (P. D. Canoll et al., 1996, Neuron 17, 229-243). We now show that GGF is able to induce differentiated oligodendrocytes to undergo a phenotypic reversion characterized by loss of MBP expression, reexpression of the intermediate filament protein nestin, reorganization of the actin cytoskeleton, and a dramatic reduction in the number of processes per cell. TUNEL analysis demonstrates that GGF is not cytotoxic for mature oligodendrocytes, but rather enhances their survival. GGF also induces the rapid activation of the PI 3-kinase and MAP kinase signaling pathways. These results further support a role for the NRGs in promoting the proliferation and survival of and inhibiting the differentiation of cells in the oligodendrocyte lineage and demonstrate that oligodendrocytes that differentiate in culture retain a substantial degree of phenotypic plasticity.
Insights
Glial growth factor (GGF) promotes oligodendrocyte progenitor proliferation and survival. Mature oligodendrocytes can revert to an immature phenotype when exposed to GGF, demonstrating significant cellular plasticity.
Area of Science:
- Neuroscience
- Cell Biology
- Developmental Biology
Background:
- Glial growth factor (GGF), a neuregulin (NRG), is known to affect oligodendrocyte progenitors.
- Previous studies showed GGF promotes proliferation and survival, while inhibiting differentiation of oligodendrocyte progenitors.
Purpose of the Study:
- To investigate the effect of GGF on mature, differentiated oligodendrocytes.
- To explore the potential for phenotypic plasticity in mature oligodendrocytes.
Main Methods:
- Treatment of differentiated oligodendrocytes with GGF.
- Analysis of myelin basic protein (MBP) expression.
- Assessment of nestin reexpression.
- Evaluation of cellular morphology and process number.
- TUNEL assay for cell viability.
- Analysis of PI 3-kinase and MAP kinase signaling pathways.
Main Results:
- GGF induced phenotypic reversion in differentiated oligodendrocytes, including loss of MBP and reexpression of nestin.
- Mature oligodendrocytes showed reduced processes per cell and cytoskeletal reorganization.
- GGF enhanced oligodendrocyte survival, with no cytotoxic effects observed.
- Rapid activation of PI 3-kinase and MAP kinase pathways was noted.
Conclusions:
- GGF plays a significant role in regulating oligodendrocyte lineage cells, promoting proliferation, survival, and inhibiting differentiation.
- Differentiated oligodendrocytes exhibit remarkable phenotypic plasticity, capable of reverting to a less differentiated state.
- NRGs are key regulators of oligodendrocyte development and plasticity.