Characterisation of Neogenin signalling pathways in polarised epithelial cells

Hayley Cox (2011). Characterisation of Neogenin signalling pathways in polarised epithelial cells MPhil Thesis, Queensland Brain Institute, The University of Queensland.

       
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Author Hayley Cox
Thesis Title Characterisation of Neogenin signalling pathways in polarised epithelial cells
School, Centre or Institute Queensland Brain Institute
Institution The University of Queensland
Publication date 2011
Thesis type MPhil Thesis
Supervisor Associate Professor Helen Cooper
Professor Alpha Yap
Total pages 83
Total colour pages 19
Total black and white pages 64
Language eng
Subjects 060106 Cellular Interactions (incl. Adhesion, Matrix, Cell Wall)
060103 Cell Development, Proliferation and Death
Abstract/Summary Neural tube formation in the early vertebrate embryo requires highly-tuned regulation of neuroepithelial cell-cell adhesion. The classical cadherins are key mediators of cell-cell adhesion in the neural tube, therefore, a mechanistic understanding of their regulation and dysregulation is paramount for gaining insight into their role in this developmental process. Compelling evidence in the literature identified Neogenin as a potential mediator of cadherin-based cell-cell adhesion, however, the nature of its interaction with the cadherins and its precise role in the regulation of cadherin signalling was largely unknown. The current investigation has used an in vitro epithelial cell model to reveal a number of potential proteins that may mediate co-operation between Neogenin and the cadherins in the early vertebrate brain. Immunofluorescence analysis revealed that Neogenin localised to the epithelial cell-cell junction of CaCo2 cells, where it colocalised with E-cadherin. This placed Neogenin in an ideal subcellular localisation to be able to interact with E-cadherin. The potential for a mutual co-operation between Neogenin and E-cadherin was identified, whereby E-cadherin depletion using siRNA resulted in a loss of Neogenin from the cell-cell junction, and conversely, Neogenin depletion resulted in a severe disruption to the integrity of the cell-cell junction basal to the zonula adherens. The current investigation also revealed that depletion of Neogenin disrupted the integrity of the microtubule cytoskeleton. More specifically, the disruption appeared to be restricted to the dynamic pool of microtubules within the cell, while the stable pool of acetylated microtubules appeared unaffected. Further, a marked increase in the number and length of dynamic microtubule plus-ends identified by the +TIP EB1/3 antibody reiterated that Neogenin may be required for the regulation of the dynamic pool of microtubules specifically. This mechanistic insight has provided a foundation for further investigation into the activity and regulation of Neogenin to determine how it may translate into more complex developmental processes, such as neurulation.
Keyword Adhesion
Caco-2
Cadherin
Epithelia
Microtubule
Neogenin
Neurulation
Additional Notes Pages to be printed in colour: 17, 20, 25, 36, 39, 45, 48, 49, 50, 53, 54, 63, 65, 72, 78, 79, 80, 81, 82.

 
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Created: Sat, 21 Apr 2012, 11:21:40 EST by Hayley Cox on behalf of Library - Information Access Service