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The Journal of Neuroscience, December 26, 2007, 27(52):14375-14382; doi:10.1523/JNEUROSCI.4456-07.2007

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Cellular/Molecular
Olig1 and Sox10 Interact Synergistically to Drive Myelin Basic Protein Transcription in Oligodendrocytes

Huiliang Li,¹ Yan Lu,² Hazel K. Smith,¹ and William D. Richardson¹

¹Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6BT, United Kingdom, and ²Medical Research Council, Clinical Sciences Centre, Imperial College London, London W12 0NN, United Kingdom

Correspondence should be addressed to William D. Richardson, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK. Email: w.richardson{at}ucl.ac.uk

The oligodendrocyte lineage genes (Olig1/2), encoding basic helix-loop-helix transcription factors, were first identified in screens for master regulators of oligodendrocyte development. OLIG1 is important for differentiation of oligodendrocyte precursors into myelin-forming oligodendrocytes during development and is thought to play a crucial role in remyelination during multiple sclerosis. However, it is still unclear how OLIG1 interacts with its transcriptional cofactors and DNA targets. OLIG1 was reportedly restricted to mammals, but we demonstrate here that zebrafish and other teleosts also possess an OLIG1 homolog. In zebrafish, as in mammals, Olig1 is expressed in the oligodendrocyte lineage. Olig1 associates physically with another myelin-associated transcription factor, Sox10, and the Olig1/Sox10 complex activates mbp (myelin basic protein) transcription via conserved DNA sequence motifs in the mbp promoter region. In contrast, Olig2 does not bind to Sox10 in zebrafish, although both OLIG1 and OLIG2 bind SOX10 in mouse.

Key words: Olig1; Olig2; Sox10; Mbp; oligodendrocyte; myelin; zebrafish; mouse; evolution; development

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Received June 7, 2007; revised Nov. 11, 2007; accepted Nov. 15, 2007.

Correspondence should be addressed to William D. Richardson, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK. Email: w.richardson{at}ucl.ac.uk

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