UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Schwann cell/axonal interactions in peripheral nerve

Wingfield Digby, KPM; (2013) Schwann cell/axonal interactions in peripheral nerve. Doctoral thesis (PhD), UCL (University College London). Green open access

[thumbnail of Wingfield Digby_Thesis_sig_removed.pdf]
Preview
Text
Wingfield Digby_Thesis_sig_removed.pdf

Download (35MB) | Preview

Abstract

Schwann cells are found in close proximity with axons from an early developmental stage, where, in adult nerve, they exist as either myelinating or non-myelinating Schwann cells. Reciprocal, contact-dependent signalling, between Schwann cells and axons, is central to the regulation of Schwann cell proliferation, survival and differentiation, as well as axonal survival. Cell adhesion molecules (CAMs) mediate homotypic and heterotypic interactions. They are required during development, in homeostatic nerve and in nerve repair following injury. Dysregulation of signal pathways and resulting aberrant CAM expression, can lead to irreversible Schwann cell/axonal dissociation, which is a hallmark of various peripheral neuropathies and nerve sheath tumours, e.g. neurofibromas in NF1 patients. In this thesis, I conducted a microarray screen to identify early mediators of Schwann cell/axonal interaction, using a Large-T (LT)-expressing Schwann cell that had spontaneously lost the ability to interact with axons, termed LT-derived (LTD) cells. This analysis revealed that multiple cell adhesion genes had become dysregulated including N-cadherin, Semaphorin-4F, Necl-4, NCAM and L1-CAM. This shift in adhesion profile suggested that a transcription factor, for example Sox2, might be the genetic lesion responsible; however, Sox2 was found not to be responsible for the LTD phenotype, although over-expression of Sox2 altered N-cadherin localisation at Schwann cell-cell junctions. Further study showed that N-cadherin was required for homotypic interactions and was an important mediator of heterotypic interactions, where heterologous N-cadherin expression in fibroblasts was sufficient to induce fibroblasts to recognise and partially associate with axons. In addition, N-cadherin was implicated in the regulation of the cell cycle; while N-cadherin silencing, in Schwann cells prior to axonal contact, was found to impede myelination in vitro. Finally, this work showed that N-cadherin and Semaphorin-4F operate at distinct stages of the interaction process, with N-cadherin mediating axonal recognition and Semaphorin-4F involved in stabilising the Schwann cell/axonal association.

Type: Thesis (Doctoral)
Qualification: PhD
Title: Schwann cell/axonal interactions in peripheral nerve
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/1419154
Downloads since deposit
241Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item