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Myosin dynamics during asymmetric stem cell division

Tsankova, Anna. Myosin dynamics during asymmetric stem cell division. 2016, Doctoral Thesis, University of Basel, Faculty of Science.

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Official URL: http://edoc.unibas.ch/diss/DissB_12905

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Abstract

Cell and tissue morphogenesis depend on the correct regulation of non-muscle Myosin 2 (NM2) but how this motor protein is spatiotemporally controlled is not fully understood. Using live cell imaging and a genetically encoded Myosin activity sensor, we found that in asymmetrically dividing Drosophila stem cells, called neuroblasts, Myosin’s biased activity depends both on cell cycle and polarity cues. During early prophase of asymmetric cell division (ACD) Myosin is recruited to the cortex prior to nuclear envelope breakdown (NEB) through the Drosophila Rho Kinase (Drok). Later, the polarity protein Partner of Inscuteable (Pins) enriches Drok at the apical cortex, where Drok phosphorylates and activates Myosin. During late metaphase Pins recruits another kinase, Protein Kinase N (PKN) specifically to the apical neuroblast cortex, which is required for the correct temporal relocalization of activated Myosin. Our results strongly suggest that the sequential activity of PKN and Drok is essential for the correct spatiotemporal regulation of apical Myosin activation and subsequent relocalization.
Furthermore, we used green-to-red photoconversion of Myosin in wild type neuroblasts to address the question about the underlying mechanism of Myosin distribution. In the current work we show that the apical and basal Myosin molecules accumulate at the cleavage furrow through two distinct spatiotemporally regulated cortical flows – a basally directed Myosin flow starting after anaphase onset followed by an opposing apical-to-basal cortical flow. Furthermore, live imaging of neuroblasts expressing constitutively active forms of Myosin showed that misregulated Myosin activity targeted to the apical or the basal cortex without being relocalized, leads to cortical deformations, ectopic furrowing and cleavage furrow mispositioning. I propose that the spatiotemporal regulation of biased Myosin activity, relocalization and thus of both cortical flows are key determinants ensuring correct cortical expansion, cleavage furrow positioning and establishment of physical asymmetry of the dividing Drosophila neuroblasts.
Advisors:Cabernard, Clemens and Affolter, Markus
UniBasel Contributors:Cabernard, Clemens and Affolter, Markus
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:12905
Thesis status:Complete
Bibsysno:Link to catalogue
Number of Pages:1 Online-Ressource (171 Seiten)
Language:English
Identification Number:
Last Modified:24 Jul 2019 12:41
Deposited On:28 Dec 2018 09:21

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