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Title: Growth and development of the Drosophila abdominal epithelium
Author: Ainslie, Anna
ISNI:       0000 0004 7660 3625
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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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.
Supervisor: Tapon, N. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available