MTUB-ANGIO · Microtubule Dynamics during angiogenesis

Microtubule Dynamics during angiogenesis

Angiogenesis is a decisive process through which new blood vessels emerge and develop from a pre-existing vasculature. This dynamic process requires that the endothelial cells, the cells that line our blood vessels, undergo profound shape changes and reorganize their scaffolding cytoskeleton. The microtubule network is precisely one of the main cytoskeletal elements of eukaryotic cells, but surprisingly the role of microtubules during angiogenesis remains poorly characterized. As angiogenesis is a process that plays crucial roles in physiology and pathology, especially during cancer development because tumor progression crucially need blood vessel recruitment, a better understanding of the regulation of angiogenesis constitutes an important health research area. Microtubules are particularly interesting to study in this context because targeting them is one of most frequently used anticancer treatment. In order to extend our knowledge on the cellular mechanisms underlying microtubule regulation and function during angiogenesis, we wanted to address the role of microtubule regulatory proteins using advanced live imaging of 3D culture of endothelial cells mimicking angiogenesis. Very interestingly, by setting-up such an approach, we found that microtubule organization and dynamics are crucial for the endothelial cells to sprout properly and build a functional vessel network. We particularly studied two aspects of microtubule: their processive growth and the symmetry of the network they are building. We assessed the role of these microtubule properties by identifying important regulators and showing their decisive angiogenic role after interfering with their function. By validating some results in vivo using zebrafish, we established a previously unexpected role for the organisation of the microtubule network in the regulation of angiogenesis.

Data: CORDIS, © European Union