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Title: Investigating how mechanical perturbation and tissue architecture affect cell behaviours in pseudostratified epithelia of Drosophila melanogaster
Author: Kirkland, Natalie Jayne
ISNI:       0000 0004 7660 4249
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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It is increasingly evident that mechanical forces play a vital role in regulating tissue development and homeostasis. During development, epithelia undergo complex morphogenesis, shaping organs by generating and responding to forces. The shape, organisation and numbers of epithelial cells are essential for overall tissue morphology. Furthermore, mature epithelia are continually subjected to stresses that may disrupt organisation of an organ. These epithelia must therefore respond to mechanical forces to maintain tissue integrity. I have used the pseudostratified epithelium (PSE) of the Drosophila wing disc to study the role of mechanical forces in regulating growth and form. PSE are found in organ precursors of many organisms due to their ability to confine the cell density required for morphogenesis. PSE tightly regulate the movement of nuclei to the apical surface prior to mitosis. This process is termed interkinetic nuclear migration (IKNM) and is essential for tissue organisation. In this thesis, I present potential mechanical regulation of IKNM dynamics through developmental increases in cell density. Such regulation may be important for regulating tissue growth. I find a role for the force generating machinery and lateral cell-cell adhesions in driving nuclear movement. These molecular effectors have differential effects on IKNM through development, suggesting that the dependency on these effectors changes in line with tissue architecture. In the second part of this thesis, I characterise a stretch-sensitive polarisation of Myosin that is downstream of Rho-mediated actin polymerisation, via Diaphanous. Cortical actomyosin is enriched at stretched junctions, in order to resist cell shape deformations and maintain epithelial integrity. I find that upon sustained stretch, actin remodelling is vital to stabilise new cell shapes. This likely enables cells to endure forces generated during morphogenesis, and subsequently stabilise new tissue structures. Overall, these findings exemplify the ability of epithelia to respond to the mechanical environment to regulate organ development.
Supervisor: Mao, Y. ; Paluch, E. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available