Lim, Shu En;
(2025)
3D Cell Shape Dynamics in Drosophila Wound Repair.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Epithelial tissues must repair wounds quickly and accurately to minimise damage and preserve organ function. Wound healing requires complex coordination of internal cell behaviours and their external environment, the basement membrane (BM), to close the gap. While the mechanisms behind wound healing in 2D epithelial sheets are well-studied, how cells change shape in 3D, particularly along the apicobasal axis, is less known. The Drosophila wing disc is composed of approximately 50µm tall cells encased by BM offers an ideal wound healing model to investigate 3D cell behaviours. This thesis aims to investigate 3D cell behaviours driving wound repair. My work builds on previous experiments in the lab that proposed a new 3D wound healing mechanism in which cell shortening accelerates wound closure by allowing cells to expand into the wound gap. We hypothesise that contractile lateral actomyosin cables in wound edge cells drive cell shortening. Using laser ablation, live imaging and quantitative analysis, I investigate how lateral cables form and their possible roles in Drosophila wing disc wound repair. I further quantified wound edge cell shape changes during repair and explored improvements to image the 3D molecular structure of lateral cables. Next, I examined the use of FRET-based tension sensors to measure forces during wound repair. I encountered experimental and technical challenges suggesting that these sensors are unsuitable to measure apicobasal forces in wounded ex vivo wing discs. Then, I genetically perturbed a variety of actomyosin-associated regulators to identify molecular regulators of lateral cable assembly. Finally, I removed BM at the wound site before wounding which appeared to alter cell shape in healing cells around the wound. Altogether, my work provides new insights into the possible molecular and mechanical mechanisms, both intracellular and extracellular, behind 3D cell shape changes during wound repair.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | 3D Cell Shape Dynamics in Drosophila Wound Repair |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212486 |
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