Woodhoo, A;
(2007)
Signals that control embryonic Schwann cell development and myelination.
Doctoral thesis , UCL (University College London).
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Abstract
The generation of mature Schwann cells from their cells of origin, neural crest cells, proceeds through two transitional steps first neural crest cells are specified to form Schwann cell precursors, which then mature into immature Schwann cells. These then generate the myelinating and non-myelinating Schwann cells found in mature nerves. Each of these steps has been well characterised phenotypically in terms of antigenic profile, survival mechanisms and morphological changes. First of all, using adapted survival assays I found that there is a range of factors that supports the survival of crest-derived glial precursor populations that generate satellite cells and Schwann cells but not of crest cells themselves. I found also that satellite cells develop earlier than Schwann cells in a number of characteristics including survival mechanisms and antigenic profile. I then examined the role of the Notch signalling pathway in the Schwann cell lineage using different in vitro and in vivo studies. I found that only Schwann cell precursor maturation is regulated by Notch signalling during early Schwann cell development. Notch signalling is also important in regulating cell division in immature Schwann cells and it acts as a negative regulator of myelination. During normal development, Notch signalling is attenuated, by a mechanism likely to involve the transcription factor Krox-20, to allow myelination to occur. Finally, in collaboration with Professors W.F. Blakemore and R.J. Franklin (University of Cambridge), I made a comparative analysis of the transplant characteristics of Schwann cell precursors and Schwann cells in two animal models of Multiple Sclerosis. We found that Schwann cell precursors outperform Schwann cells in myelination potential, survival and migratory properties in these animal models.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Signals that control embryonic Schwann cell development and myelination |
| Identifier: | PQ ETD:593604 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1446266 |
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