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dc.contributor.supervisor Namaka, Michael (Pharmacy) en_US
dc.contributor.author Vora, Parvez Firoz
dc.date.accessioned 2012-08-23T16:53:40Z
dc.date.available 2012-08-23T16:53:40Z
dc.date.issued 2012-08 en_US
dc.date.issued 2011-04 en_US
dc.date.issued 2010-10 en_US
dc.identifier.citation Vora, P., Pillai, P., Mustapha, J., Kowal, C., Shaffer, S., Bose, R., Namaka, M., Frost, E.E. (2012) “CXCL1 does not regulate Oligodendrocyte progenitor cells via calcium signaling” Experimental Neurology 236(2), 258-267. en_US
dc.identifier.citation Vora, P., Pillai, P.P, Zhu, W., Mustapha, J., Namaka, M. and Frost, E.E. (2011) “Differential effects of growth factors on Oligodendrocyte progenitor migration” Eur. Journal of Cell Biology 90(8), 649-656. en_US
dc.identifier.citation Vora, P., Mina, R., Namaka, M., and Frost, E. E. (2010) “A novel transcriptional regulator of myelin gene expression: implications for neurodevelopmental disorders” Neuroreport 21, 917-921. en_US
dc.identifier.uri http://hdl.handle.net/1993/8463
dc.description.abstract Oligodendrocytes (OL) are the myelinating cells of the central nervous system (CNS). A series of complex cell signaling events in the CNS ensures successful myelination. Various molecular cues including growth factors, transcription factors and cytokines regulate myelination by inducing OL migration, proliferation and differentiation. Plateletderived growth factor A (PDGF-A) and fibroblast growth factor 2 (FGF2) are two of the most well characterized regulators of OP migration. The current study hypothesizes that PDGF-A and FGF2 regulate the migration of OP through transient activation of the extracellular signal-regulated protein kinase (ERK) signaling pathway. The results show that activation of ERK is required for OP migration. It also demonstrates the significance of threshold levels of growth factors and temporal regulation for OP migration. Furthermore, the chemokine CXCL1 has been shown to play a critical role in regulating the dispersal of OP during development, although the mechanisms underlying this regulation are unknown. Previous studies have shown that calcium flux is required for OP migration. CXCL1 induces calcium flux in cells; therefore we hypothesized that CXCL1 inhibition of OP migration was regulated via changes in intracellular calcium flux. However, our results show that CXCL1 inhibition of OP migration is independent of calcium signaling. In addition, we show that CXCL1 inhibition of OP migration is specific to PDGF-A induced migration. Lastly, the current study identifies a transcriptional regulator, methyl-CpG-binding protein 2 (MeCP2) as regulating the expression of myelin specific genes in a transgenic mouse. Interestingly, gene expression of myelin associated proteins myelin basic protein (MBP), myelin associated glycoprotein (MAG)and proteolipid protein (PLP), which play an important role in regulation of OL differentiation and subsequent formation of myelin of the myelin sheath, where found to be dysregulated. Overall, these findings reveal previously unknown roles of various intrinsic factors in successive phases of OL development. It aims to provide a better understanding of complexity to myelin development, function and disease. en_US
dc.publisher Experimental Neurology (Elsevier) en_US
dc.publisher European Journal of Cell Biology (Elsevier) en_US
dc.publisher Neuroreport (Wolters Kluwer Health) en_US
dc.rights info:eu-repo/semantics/openAccess
dc.subject oligodendrocyte en_US
dc.subject CXCL1 en_US
dc.subject MeCP2 en_US
dc.subject cell migration en_US
dc.subject PDGF en_US
dc.subject FGF en_US
dc.title Molecular regulation of myelination by Oligodendrocyte Progenitor cells en_US
dc.type info:eu-repo/semantics/doctoralThesis
dc.degree.discipline Pharmacy en_US
dc.contributor.examiningcommittee Eisenstat, David (Biochemistry) Ivanco, Tammy (Psychology) Alessi-Severini, Silvia (Pharmacy) Davis, Christine (Pharmacy) Kennedy, Timothy (McGill University) en_US
dc.degree.level Doctor of Philosophy (Ph.D.) en_US
dc.description.note October 2012 en_US


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