About the talk: Our blood vessel system is an extremely complex network consisting of distinct vessel types including arteries, capillaries and veins. These different vessel beds also experience local environmental cues that drive tissue specific vascular network through organotypic differentiation. Transmembrane integrin heterodimers formed by a-and β-subunits are the major adhesion receptors that reside at the endothelial cell-matrix interface and interpretenvironmental cues. Upon ligand binding integrins undergo a conformational change and reorganise into activated clusters called Focal Adhesions (FAs) that provide a physical connection between the intracellular acto-myosin machinery and the ECM. The connection to acto-myosin is established by integrin adaptor molecules, including talins. By utilising the live imaging capacity of the zebrafish we have examined how FAs, controlendothelial cell (EC) dynamics in live flow pressured vasculature. To do this, we generated a zebrafish mutant, deficient for the integrin adaptor protein Talin1. Loss of FAs in talin1 mutants, leads to compromised F-actin rearrangements, which perturb EC elongation and cell-cell junction linearisation during vessel remodelling.Chemical induction of actin polymerisation can restore these cellular phenotypes, suggesting a recovery of actinrearrangements that are sufficient to allow cell and junction shape changes. We have further explored how tissue specific ECM signals can underlie susceptibility to a vascular disease called Cerebral Cavernous Malformations (CCM, cavernoma). CCM is a disease whereby focal clones of defective ECs give rise to distinctive bulging vascular lesions. Underlying the formation of these expanded and fragile lesions are a discrete set of cellular defects, including reduced cell-cell adhesion, cellular thinning and cells spreading. It is currently not understood why CCMs develop specifically in brain vasculature. To study this, we utilised our model of 3D bioengineered vasculature and identified that in the CCM microenvironment HyaluronicAcid homeostasis is perturbed. By growing 3D tubes in ECMs containing distinct forms of HA we further showed that modifying HA content alters CCM outcome.