In this thesis, I test the hypothesis that a group of adhesion molecules, known as integrins, regulates the behaviour of neuroepithelial precursors. Integrins are a major group of receptors for extracellular matrix proteins and cell surface adhesion molecules. An enriched population of neuroepithelial precursors can be grown <I>in vitro</I> as free floating aggregates of cells under the influence of epidermal growth factor (EGF). I have used these aggregates, known as 'neurospheres', to model <I>in vitro</I> the development of neuroepithelial precursors <I>in vivo</I>. Neurosphere cells <I>in vitro</I> will undergo cell death, division, differentiation and migration in a similar manner to neuroepithelial precursors <I>in vivo</I>. I have characterised the integrins expressed by neurosphere cells and using integrin ligands from the extracellular matrix and integrin antagonists I have determined the role of these integrins in regulating neuroepithelial precursor migration and division. I found that neurosphere cells express a specific and limited set of integrins in culture. Specifically they express α5β1, α6Aβ1, α6Bβ1, αvβ1, αvβ5 and αvβ8 but do not express α1β1, α2β1, α3β1, α4β1, αvβ3. Furthermore, different integrins on these cells regulated cell division and migration. Specifically, α6β1 regulated cell migration but did not regulate cell division. In contrast, a second as yet uncharacterised, β1 integrin did regulate the division of these cells. These <I>in vitro</I> results emphasise the important role of integrin-extracellular matrix interactions in the development of neuroepithelial precursors. Finally, I discuss the role of an extracellular matrix molecule, tenascin-C, in the development of neuroepithelial cells <I>in vivo</I>. Taken together, these results support the idea that signalling through integrins is important in controlling the development of neuroepithelial precursors.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:605014 |
| Date | January 1997 |
| Creators | Jacques, T. S. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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