Final Report Summary - RESHAPE (Reverse engineering of vascular patterning through mosaic in vivo analysis of endothelial cell shape regulation)
The Reshape project set out to unravel vascular patterning by reverse engineering the shape and transitions of vascular networks by looking in detail at the individual building blocks that make up the vascular tubes, the endothelial cells. As a new vascular network forms, cells assemble first a primitive network through sprouting and branching, followed by a poorly understood remodelling process that ultimately shapes arteries, veins and all the vessels of different sizes. The Reshape project developed mosaic approaches to label and track individual cells within the network in order to characterise the complexity of cell shapes at the different locations and during the transitions from primitive to remodelled network. Furthermore, using these approaches in mouse and zebrafish, the project studied how endothelial cells shape is regulated by extrinsic signals or intrinsic mechanisms in order to understand how the different shapes are achieved. A combination of sophisticated imaging, genetic inducible manipulation, computational analysis and modelling established a series of novel principles of endothelial cell shape regulation, as well as a totally unexpected degree of cell movement within the vessels. The latter finding superseded the original hypothesis, and gave rise to new ideas of how genetic regulatory mechanisms and cell mechanosensing under blood flow orchestrate cell and vessel shape changes that form the network. More than 20 publications and additional reviews arose from the project, and new grants that follow the mechanisms of endothelial rearrangements under flow have been made possible. Three post-docs have established their own labs at prestigious Institutions in the US, Japan and Europe, signifying successful training of excellence in science.