Schmid, Daniela. Functional role of the overexpression of the myelin and lymphocyte protein MAL in Schwann cells. 2013, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_10673
To elucidate a functional link between MAL overexpression and retarded myelination, primary mouse Schwann cell cultures were investigated. We could show that the induction of the CREB signaling pathway is functional, indicating that Schwann cells overexpressing MAL are not less responsive to axonal signals. Despite functional activation of the cAMP signaling pathway, significantly reduced mRNA expression levels of P0 and p75NTR were detected in untreated Schwann cells overexpressing MAL. This study revealed that most transcription factors known to modulate P0 expression were not altered in Schwann cells overexpressing MAL. During development, Schwann cells depend on accurate levels of different growth factors. To determine whether the delayed onset of myelination might be caused by a deficient downstream signaling of a particular growth factor, Schwann cells were treated with neuregulin1, nerve growth factor or fibroblast growth factor 1. However, none of the investigated growth factors could ameliorate the reduced expression of P0 and p75NTR in MAL-overexpressing Schwann cells.
MAL-overexpressing Schwann cells were further investigated using a whole genome expression analysis. Most transcripts of genes implicated in Schwann cell development, differentiation and maintenance were not affected by MAL-overexpression. However, we identified a number of genes associated with cytoskeleton organization and components of the basal lamina that are regulated in a MAL-dependent manner. Especially during development and differentiation of Schwann cells, major changes in cellular processes and architecture are crucial for accurate radial sorting and myelination, proposing them as novel candidates for influencing myelination.
|Committee Members:||Kampfhammer, J.|
|Faculties and Departments:||03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neurobiology (Schaeren-Wiemers)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||138 Bl.|
|Last Modified:||30 Jun 2016 10:55|
|Deposited On:||26 Mar 2014 13:30|
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