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Title: The role of integrins in oligodendrocyte differentiation
Author: Buttery, P.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1999
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Oligodendrocytes and their precursors express a defined repertoire of integrin receptors, consisting of the heterodimers αvβ1, αvβ3, αvβ5, αvβ8 and a6β1. A role for the αvβ1 receptor has recently been defined in the migratory behaviour of oligodendrocyte precursors, and this project describes and extension of such work to examine the involvement of integrins in cellular differentiation and survival in this lineage. Using enriched populations of rodent oligodendrocyte precursors in simplified in vitro cell culture system several observations have been apparent: Firstly, there is evidence that β1 integrins are involved not only in migration of the precursors, but also in survival of the cells at all stages. In addition, morphological differentiation of the cells, which involves the elaboration of a complex meshwork of processes and subsequent myelin sheet formation, also turns out to be enhanced by a substrate of laminin-2, which is a potential ligand for the α6β1 integrin; correspondingly, it is shown that β1 integrins are also required for optimal morphological differentiation of the cells. Cellular differentiation is marked by a switch between an immature pattern of integrin expression (αvβ1, αvβ8 and α6β1) and a mature pattern of expression (αvβ3, αvβ5, αvβ8 and α6β1), and this switch is shown to be inhibited by the fibroblast growth factor, FGF-2. Upon withdrawal of FGF-2 therefore, the cells differentiate, exhibiting a burst of tyrosine phosphorylation; a group of tyrosine phosphorylated proteins are demonstrated to be associated with the β3 integrin subunit at this state, a subunit whose expression was inhibited by FGF-2. Finally, the different subunits β1, α6 and β5 show distinct spatial patterns of expression in differentiating cells, and evidence is presented to suggest the presence of an additional β1-associated α subunit, that is thus far unidentified.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available