Cazzagon, Giulia;
(2023)
Investigating the role of SCAR-Arp2/3 dependent cortical remodelling in asymmetrically dividing Drosophila neuroblasts.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Division is one of the most important events in the life of a cell, which ensures that the genetic material and the entire set of cellular components segregate in the correct way between the two daughter cells. To divide, cells have to undergo profound shape changes in a timely manner. While the actin cortex is known to control the changes in cell shape that accompany division, much remains to be discovered about the molecular and cellular mechanisms that control cortical remodelling and that coordinate asymmetric stem cell divisions. In this work, I identify the SCAR-Arp2/3 pathway as a potential new regulator of the polarised shape changes in anaphase that help drive asymmetric stem cell divisions in Drosophila melanogaster. I show that filopodia-like membrane protrusions are found at the apical cortex in metaphase and their organization is dependent on Arp2/3. Interestingly, SCAR localizes preferentially at the apical cortex of neural stem cells, and both SCAR and the membrane protrusions disappear from the apical cortex as cells undergo cortical expansion when they enter anaphase. Finally, cells depleted of SCAR or the Arp2/3 complex show a disorganized microtubule spindle and cortical defects at the end of mitosis, suggesting a role for Arp2/3 in stabilizing cortical shape and tension at the metaphase-anaphase transition. This is surprising as the branched actin network nucleated by Arp2/3 is known for its role in trafficking, motility of organelles and cell migration, rather than in cell division, which depends on Formin-based actin nucleation. Through this work I propose a role for the SCAR-Arp2/3 pathway in maintaining proper cortical organization in the dividing neuroblasts to aid proper asymmetric division, hence suggesting a new cellular mechanism that contributes to asymmetric cell division in the Drosophila neural stem cells.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the role of SCAR-Arp2/3 dependent cortical remodelling in asymmetrically dividing Drosophila neuroblasts |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. 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 > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10168217 |
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