Pitsidianaki, Ioanna; (2025) Investigating the structure and function of the microtubule network in amoeboid swimming migration of Drosophila adipocytes. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Cell migration is crucial for many normal developmental and pathological processes. Migrating cells adopt various modes of motility, depending in different ways on the cytoskeletal components. Adhesiondependent migration is well known to rely on actin polymerization and traction forces. In this process, microtubules (MTs) transport secretory vesicles containing integrins and other components to facilitate cell adhesion. Additionally, MTs play a critical role in cell polarization and organization of intracellular organelles. In contrast, the role of MTs in adhesion-independent migration—often referred to as “amoeboid” migration—remains poorly understood. UsingDrosophila pupal adipocytes, called fat body cells (FBCs), as an in vivo model for studying adhesion-independent, swimming migration, I demonstrate that the MT network is essential for this mode of locomotion. MTs provide mechanical support and regulate FBC migration through EB1 signalling. Furthermore, I show that the nucleus in FBCs is positioned at the cell front, and this positioning correlates with both the speed and directional persistence of migration. Lastly, I investigate the role of endocytosis as part of the ”molecular paddling” mechanism of migration. I reveal that endocytosis is required for migration, impacting cortical actin distribution in FBCs. These findings highlight the critical role of the MT network in regulating swimming migration and expand our understanding of adhesion-independent motility.

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