Mitotic control of endothelial cell identity

  • Sabrina Ghadaouia

Student thesis: Phd


Mitosis is a complex and tightly regulated mechanism that is absolutely essential to the growth and the development of an organism. Yet, the cell division process is highly disruptive, as it involves strong modification of cell morphology, as well as a complete reorganisation and redistribution of the cytoskeleton. As such, mitosis is often considered incompatible with other morphogenetic events, such as cell migration. Hence, deciphering the strategies used by cells to integrate cell division with cell migration would provide a better understanding of embryo morphogenesis. To study this integration, the formation of intersegmental blood vessels (ISVs) in the zebrafish embryo is a particularly well-suited model. This angiogenic process relies on the collective migration of a group of endothelial cells (ECs) from the first embryonic artery, the dorsal aorta, led by a tip cell, a highly motile EC that guides its neighbours the stalk cells into forming a new blood vessel. Notably, this highly dynamic tip cell undergoes mitosis whilst guiding collective migration, making ISV formation a perfect model to study the integration of mitosis with migration. Interestingly, tip cells have been shown to undergo an asymmetric division in this context, giving rise to daughter cells of different size and of different identity. This asymmetry seems crucial to maintain the tip-stalk hierarchy, ensuring coordinated collective migration and angiogenesis. However, the mechanisms involved in the establishment of this postmitotic asymmetry remain unclear. In this thesis, I use a combination of in vivo liveimaging and in vitro assays to define the regulation of post-mitotic daughter cell size asymmetry. I show that the microenvironment impacts cell morphology in mitosis, therefore determining post-mitotic asymmetry. I then reveal the key role of interphase geometry in driving asymmetric division. Finally, I investigate the role of the mitotic spindle in the establishment of post-mitotic daughter cell asymmetry during tip cell division.
Date of Award1 Aug 2021
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorChristoph Ballestrem (Supervisor) & Shane Herbert (Supervisor)


  • Mitosis
  • Asymmetric division
  • Cell shape
  • Spindle
  • Spindle positionning
  • Spindle movement
  • Micropatterning

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