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Investigating the role of mechanical forces in heterogeneous tissue patterning

Blackie, Laura; (2018) Investigating the role of mechanical forces in heterogeneous tissue patterning. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Epithelial cells do not develop in isolation but are mechanically-coupled to their neighbours through their adherens junctions. Consequently, the mechanical forces associated with cell morphogenesis are transmitted across the tissue. Many epithelial tissues can be considered as heterogeneous in that they contain multiple cell types of distinct morphologies. In such tissues, the forces exerted on an individual cell by its neighbours might vary both spatially and temporally during morphogenesis. How the mechanical forces produced during morphogenesis are coordinated across a heterogeneous tissue is unknown. Furthermore, whether the individual cells can sense and respond to mechanical force is unclear, as are the mechanisms that might mediate this. During my PhD, I used the Drosophila retina as a model tissue to investigate the role of mechanical forces during heterogeneous tissue morphogenesis. My work revealed that the Notch signalling pathway and differential adhesion through Nephrin-like adhesion molecules regulate a stereotyped step of cell intercalation between four glial cells that occurs during retinal development. Although in this context cell intercalation is driven by an intrinsic mechanism, it also requires insulation from the high extrinsic forces generated by the neighbouring cells. My work indicates that the properties of a cell’s cytosolic medial myosin meshwork vary dependent on cell fate or shape. Importantly, my results highlight a function for the cytosolic actomyosin meshwork in determining heterogeneous cell shapes. Additionally, my work shows that the medial meshwork is mechano-sensitive and that it can drive cell type-specific responses to mechanical force. Finally, my results show that the sensory photoreceptor neurons require spatial confinement by the glial cone cells in order to undergo morphogenesis. Altogether, my PhD work provides new insights into how different cell types interact through and respond to mechanical forces to bring about coherent tissue patterning.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Investigating the role of mechanical forces in heterogeneous tissue patterning
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
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.ucl.ac.uk/id/eprint/10054496
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