Oligodendrocyte lineage (Olig) genes in development and disease. (360G-Wellcome-084299_Z_07_Z)

£525,692

We will investigate the functions and regulation of the transcription factors Olig1 and Olig2. Olig1/2 are important for oligodendrocyte (OL) development and regeneration; Olig2 is also required for specification of spinal motor neurons (MNs) and other types of neurons in the brain. Olig proteins interact with a diverse set of transcriptional co-factors including SoxE proteins, nuclear hormone receptors and homeodomain proteins. We will investigate whether Olig proteins switch binding partner s during successive stages of MN and OL development and whether this contributes to lineage progression. We have evidence that phosphorylation of Olig2 by PKA is required for Olig2 dimer formation and its ability to specify MNs in chick electroporation experiments. We will build on this finding to discover whether and how PKA phosphorylation is involved in MN/OL development. In parallel, we will investigate mechanisms of nuclear translocation of Olig1, which is crucial for generation of new O Ls during demyelinating disease. We have evidence that FGF signalling regulates nuclear accumulation of Olig1 and we will build on this observation. This series of experiments combines biochemical, cellular and transgenic approaches and will provide insights into the biology of Olig proteins and their roles in development and disease.

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Grant Details

Amount Awarded 525692
Applicant Surname Richardson
Approval Committee Molecular and Cellular Neuroscience Funding Committee
Award Date 2008-02-11T00:00:00+00:00
Financial Year 2007/08
Grant Programme: Title Project Grant
Internal ID 084299/Z/07/Z
Lead Applicant Prof William Richardson
Other Applicant(s) Dr Huiliang Li
Partnership Value 525692
Planned Dates: End Date 2011-09-30T00:00:00+00:00
Planned Dates: Start Date 2008-04-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London