Regulation of endothelial cell morphogenesis, including collective migration, is a critical factor for building functional vessels. Accordingly, many angiogenesis-related diseases such as cancer are associated with perturbed EC polarity and vessel morphology, even though the involved molecular players are largely unknown. The role of microtubules has been deeply overlooked in the field although they are increasingly considered as crucial players in differentiation and development programs. By using a physiologically relevant environment, recent studies, including from our lab, have progressively shifted the longstanding view of a dominating role of actin towards an active function for microtubules in 3D cell migration and morphogenesis.
MT targeting agents, including anti-cancer drugs, are well-known anti-angiogenic molecules, pointing towards the relevance of microtubules in supporting vessel formation and calling for a better mechanistic understanding of their function in angiogenesis. By using 3D cultures of primary endothelial cells that balance physiological relevance with ease of manipulation and imaging, and zebrafish models, our lab wants to address in detail the previously underappreciated role of microtubules during vascular bed-specific angiogenesis. We are performing functional screens, detailed cell biology based on up-to-date microscopy techniques as well as unbiased interatomic analyses to establish an unprecedented understanding of MT function during endothelial morphogenesis.