| First Author | Stritt C | Year | 2009 |
| Journal | Nat Neurosci | Volume | 12 |
| Issue | 4 | Pages | 418-27 |
| PubMed ID | 19270689 | Mgi Jnum | J:150528 |
| Mgi Id | MGI:3850914 | Doi | 10.1038/nn.2280 |
| Citation | Stritt C, et al. (2009) Paracrine control of oligodendrocyte differentiation by SRF-directed neuronal gene expression. Nat Neurosci 12(4):418-27 |
| abstractText | 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. |
