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Control of PAR polarity during early embryogenesis

Ng, KangBo; (2025) Control of PAR polarity during early embryogenesis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Cell polarity conferred by the highly conserved PAR polarity network underlies a myriad of developmental processes, including tissue patterning, cell migration, and asymmetric cell division. Consequently, the PAR network is continuously redeployed in a wide range of cell and tissue types during development. Yet, how the same network is able to adapt to changes in cellular contexts and developmental cues are poorly understood. Here, I sought to address this by taking advantage of the highly tractable early C. elegans embryo as a model. Specifically, by comparing and contrasting PAR polarisation between the zygote and P blastomeres, which have stark differences in how their polarity manifests, I aimed to uncover general design principles that help the network adapt during development. A variety of approaches, including chemical-/opto-genetics, biophysical manipulations, and mathematical modelling was used to explore this question. I found that despite overt differences in how polarity emerges between the zygote and P blastomeres, the pathways used to polarise are surprisingly conserved, suggesting that the network is intrinsically adapted to polarise in diverse contexts. Instead, to coordinate changes in polarity requirements during development, cells use distinct cues. I uncovered, to my knowledge, a new developmental cue which allows cells to coordinate cell division and cell polarity: cleavage-furrow flows. Finally, I found a potential role of CDK-1 in driving oscillations in the PAR network. These oscillations seem to optimise polarisation, by allowing the system to navigate differing requirements associated with either polarity establishment or maintenance. Disrupting these oscillations led to reduced robustness to dosage changes and sensitivity to ectopic cues, suggesting that oscillations confer developmental robustness.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Control of PAR polarity during early embryogenesis
Language: English
Additional information: Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/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 > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10204252
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