Davis, C.M.;
(2009)
Signalling pathways regulating Schwann cell survival and differentiation.
Doctoral thesis , UCL (University College London).
Abstract
The generation of mature Schwann cells from the neural crest occurs by a transition through two intermediate cell types, namely the Schwann cell precursor and the immature Schwann cell. Immature Schwann cells mature into the myelinating and non-myelinaling Schwann cells present in the adult nerve. These cell types are well characterised and can be readily distinguished from one another by their distinct antigenic profile, survival responses, and morphological changes. In this study I investigated the effects of BMP in the Schwann cell lineage in vitro. I found that BMP2/4 acts to maintain the immature Schwann cell type by promoting its differentiation from the Schwann cell precursor and inhibiting the upregulation of myelin proteins. I also found that survival responses to BMP2/4 differ between embryonic and postnatal Schwann cell. I examined the role of STAT3 in Schwann cells both in vitro and in vivo using mice with a conditional mutation of STAT3 specifically in Schwann cells. I found that STAT3 is activated by, and supports survival following stimulation by autocrine factors secreted by Schwann cells both in vitro and following nerve injury in vivo. I also discovered that STAT3 promotes the expression of myelin proteins in vitro and that it is involved in the timing of demyelination following sciatic nerve injury. I also investigated the repression of the transcription factor c-Jun, by itself and by Krox-20, in immature Schwann cells and found that this occurs mainly at the protein, rather than the transcriptional level.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Signalling pathways regulating Schwann cell survival and differentiation |
| Language: | English |
| Additional information: | Authorisation for digitisation not received |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/17978 |
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