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  Paracrine control of oligodendrocyte differentiation by SRF-directed neuronal gene expression.

Stritt, C., Stern, S., Harting, K., Manke, T., Sinske, D., Schwarz, H., et al. (2009). Paracrine control of oligodendrocyte differentiation by SRF-directed neuronal gene expression. Nature Neuroscience, 12(4), 418-427. doi:10.1038/nn.2280.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7DF9-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7DFA-7
Genre: Journal Article
Alternative Title : Nat. Neurosci.

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 Creators:
Stritt, Christine, Author
Stern, Sina, Author
Harting, Kai, Author
Manke, Thomas1, Author              
Sinske, Daniela, Author
Schwarz, Heinz2, Author
Vingron, Martin3, Author              
Nordheim, Alfred, Author
Knöll, Bernd, Author
Affiliations:
1Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433547              
2Max Planck Society, ou_persistent13              
3Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 Abstract: In neurons, serum response factor (SRF)-directed transcription regulates migration, axon pathfinding and synapse function. We found that forebrain-specific, neuron-restricted SRF ablation in mice elevated oligodendrocyte precursors while inhibiting terminal oligodendrocyte differentiation. Myelin gene and protein expression were downregulated and we observed a lack of oligodendrocytes in mixed neuron/glia and oligodendrocyte-enriched cultures derived from Srf-/- mutants. Ultrastructural inspection revealed myelination defects and axonal degeneration in Srf-/- mutants. Consistent with our finding that neuronal SRF depletion impaired oligodendrocyte fate in a non–cell autonomous manner, neuron-restricted expression of constitutively active SRF-VP16 affected neighboring oligodendrocyte maturation. Genome-wide transcriptomics identified candidate genes for paracrine regulation of oligodendrocyte development, including connective tissue growth factor (CTGF), whose expression is repressed by SRF. Adenovirus-mediated CTGF expression in vivo revealed that CTGF blocks excessive oligodendrocyte differentiation. In vitro, CTGF-mediated inhibition of oligodendrocyte maturation involved sequestration and thereby counteraction of insulin growth factor 1–stimulated oligodendrocyte differentiation.

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Language(s): eng - English
 Dates: 2009-03-08
 Publication Status: Published in print
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Title: Nature Neuroscience
  Alternative Title : Nat. Neurosci.
Source Genre: Journal
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Pages: - Volume / Issue: 12 (4) Sequence Number: - Start / End Page: 418 - 427 Identifier: ISSN: 1097-6256