Mechanisms of Schwann cell myelination and dedifferentiation: relevance to nerve repair and pathology. (360G-Wellcome-091119_Z_10_Z)

£1,284,915

In view of the importance of Schwann cell dedifferentiation for nerve pathology/repair, it is surprising how little is known about the relevant transcriptional programmes. Our identification of two transcriptional regulators in Schwann cells, Notch and c-Jun, that control this process is therefore a significant step forward. (A) We will test (i) whether c-Jun-dependent Schwann cell signals control neuronal survival/growth after injury and whether such signals promote neuropathic pain (ii) h ow Schwann cell c-Jun controls breakdown of axon-growth inhibitors and organises cell morphology to generate growth-substrate for axons (iii) the direct transcriptional regulation by c-Jun in Schwann cells of genes important for nerve repair. (B) We will analyse how (i) c-Jun and Notch pathways cross-talk in Schwann cells of injured nerves and (ii) Notch inhibits repair while c-Jun promotes it. (C) Lastly we will test whether, in principle, c-Jun and Notch signalling can be targeted to i mprove pathology in animal models of inherited and acquired demyelinating disease, and nerve regeneration following injury. We will use genetically modified mice, including mice with conditional inactivation of c-Jun, conditional activation of c-Jun, conditional inactivation of Notch, inactivation of the c-Jun/Notch ubiquitin ligase Fbw7 and the transcription factor Olig1, and genetic models of demyelinating disease.

Where is this data from?

This data was originally published by The Wellcome Trust. If you see something about your organisation or the funding it has received on this page that doesn't look right you can submit a grantee amendment request. You can hover over codes from standard codelists to see the user-friendly name provided by 360Giving.

Grant Details

Amount Awarded 1284915
Applicant Surname Jessen
Approval Committee Neurosciences And Mental Health
Award Date 2010-02-18T00:00:00+00:00
Financial Year 2009/10
Grant Programme: Title Programme Grant
Internal ID 091119/Z/10/Z
Lead Applicant Prof Kristjan Jessen
Other Applicant(s) Prof Rhona Mirsky
Partnership Value 1284915
Planned Dates: End Date 2017-05-31T00:00:00+00:00
Planned Dates: Start Date 2010-06-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London