Ainslie, Anna;
(2019)
Growth and development of the Drosophila abdominal epithelium.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The growth of multicellular organisms and their organs is a tightly regulated process, ensuring that each animal of a given species grows to its characteristic size and shape. A key regulator of organ size during development is Hippo signalling, a highly conserved tumour-suppressor pathway, which controls the activity of pro-growth transcriptional co-activator Yorkie (Yki). Multiple upstream cues regulate the activity of the Hippo pathway, including cell-cell contacts and mechanical strain. In this project I studied growth control in the Drosophila histoblasts, the precursor cells that give rise to the adult abdominal epidermis during pupal development. Histoblasts are specified during embryogenesis, however they remain quiescent until pupariation. During the early pupal stages, histoblasts undergo extensive proliferation, replacing the surrounding larval epithelial cells (LECS), which extrude from the epithelial layer and undergo apoptosis. Once histoblasts have covered the surface of the pupal abdomen, they undergo tissue growth arrest. Histoblast nests provide a highly genetically tractable model system that enables live imaging of cell proliferation and arrest of a developing tissue in vivo. A bespoke image analysis pipeline was created to segment and track histoblasts, with which I performed a detailed analysis of temporal and spatial changes of morphogenesis over an extensive developmental period. Furthermore, the histoblast model allows investigation of mechanical forces on tissue growth in a live, developing tissue. This was done through alteration of the mechanical environment of the histoblasts by genetically interfering with the surrounding LECs. I found that proliferation rate was unaffected by stretching or constraint, whereas changing the state of the basal extracellular matrix (ECM) has an impact on Yki activity and proliferation rates. Finally, I looked at possible biochemical mechanisms of Yki regulation by screening members of the Hippo signalling network, and I identified several candidates for further investigation.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Growth and development of the Drosophila abdominal epithelium |
| Event: | UCL (University College London) |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2019. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/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 UCL > Provost and Vice Provost Offices 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 |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10065643 |
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