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Gough, Chelsey Lynn

University of British Columbia

Cytokinesis is the final stage of cell division in which the dividing cell is physically separated in two through the function of the contractile ring. The contractile ring is a highly resilient molecular machine which can properly function even in the absence of some of structural components and regulators. Additionally, the function, position, and orientation of the contractile ring are spatially modified in developing animals to regulate morphogenesis. Although essential regulators of cytokinesis have been identified through previous forward genetic screenings, the molecular mechanisms underlying these spatial and robust controls of cytokinesis remain elusive. To identify novel cytokinesis regulators involved in these processes, we performed a high-throughput RNAi suppressor screening using a gain-of-function mutant of actin. We obtained a total of 483 early embryonic genes that suppress lethality in an act-2 mutant background. Two parallel secondary screenings were then performed using the identified candidate genes. The first screening aimed to identify regulators of spatial cytokinesis control such as asymmetric ring closure, asymmetric ring positioning, and contractile ring rotation during three early stages of embryogenesis. A total of 108 genes were found to regulate at least one of these three forms of spatially controlled cytokinesis. Secondly, we performed a screening in an act-2(or295) background to identify regulators of cytokinesis robustness. We identified twelve genes that resulted in moderate to severe cytokinetic defects, including two novel regulators, evl-20 and lpin-1. Our study will serve as a useful database for the development of future hypotheses and provide insights into the precise regulation of cytokinetic mechanisms in tissues. [An errata to this thesis was made available on 2024-06-24.]

Text

2024-04-15

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87830

Zoology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/