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Title: Role of actomyosin-mediated tension in a tissue on spindle positioning during mitosis
Author: Lam, M. S. Y.
ISNI:       0000 0004 8498 4704
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Almost all animal cells construct a mechanically rigid and contractile actomyosin cortex as they enter mitosis. The process is best understood in isolated cells, where this cortex helps drive mitotic cell rounding - generating space for spindle morphogenesis. The actomyosin cortex has also been suggested to play a role in spindle orientation, by regulating cell shape and by polarizing canonical spindle-orienting proteins. Furthermore, extrinsic force via actin-based retraction fibers in isolated cells has been proposed to reposition the spindle - implying that the process is mechanosensitive. However, cells in a tissue sit in much more complex biochemical and mechanical landscapes, where the role of the actomyosin cortex is unclear. To shed light on this, I investigate the role of the mitotic actomyosin cortex and mechanical tension in spindle positioning within an epithelium - the Drosophila notum. I find that i) mitotic rounding occurs in a crowded tissue even when levels of actin and myosin activity are compromised; ii) actin and myosin have cell-autonomous roles in centrosome movement and spindle centering; and iii) mechanical tension appears to play a non-autonomous role in orienting the spindle. Although spindle alignment has been shown to be along the cell long axis in many systems, I find that this is not always the case. Cells under isotropic tension actively orient their spindles along the long axis, while this is less efficient in cells under lower tension due to crowding of the tissue or reduced myosin activity, despite having a well-defined long axis. Finally, I suggest a model of dynamic spindle positioning in an epithelium, where the mitotic actomyosin cortex provides mechanical rigidity to facilitate efficient and balanced pulling forces on the centrosomes by astral microtubules, and where extracellular tension through actomyosin activity and cell-cell adhesion provides external cues for spindle orientation to cell long axis.
Supervisor: B. A. U. M., B. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available