Molecular mechanisms governing the plasticity of cellular boundaries in confluent epithelial monolayers are poorly characterised. In this thesis, we report a drastic reorganisation of cellular boundaries, provoked by the prolonged withdrawal of EGF from non-malignant mammary epithelial cells, MCF10A and HMT-3522 cells. EGF withdrawal induces actin-rich interdigitations that protrude into neighbouring cells and are enriched in desmosomes. These protrusions allow the cellular sheets to resist mechanical and osmotic perturbation. Mobility of the cells within monolayers is also restricted. Overexpression of constitutively active Rac opposes interdigitations and induces membrane ruffling. EGF application reverses the interdigitations rapidly in a process that requires actin polymerisation and actomyosin contraction. We report here a simple in vitro system that can be utilised as a visual readout to dissect novel signaling pathways specific to EGFR activation and mammary morphogenesis. This thesis focuses on the initial efforts to characterise this dramatic remodeling of cellular boundaries and will discuss the potential investigations that can be pursued further hereon.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:666697 |
| Date | January 2014 |
| Creators | Tang, Wai Ying Yvonne |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://livrepository.liverpool.ac.uk/2008147/ |
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