Rho signaling and mechanical control of vascular development

Abstract

To discuss how mechanical cues and Rho signaling contribute to control of vascular development and hematopoiesis. Rho guanine trinucleotide phosphatases are ubiquitious regulators of cytoskeletal structure and tension generation. Recent work shows that Rho-dependent mechanical interactions between cells and extracellular matrix regulate cell fate switching in capillary endothelial cells and megakaryocytes in vitro, as well as angiogenesis, vascular permeability, leukocyte migration and platelet formation in vivo. Signaling pathways that link integrins and tension-dependent changes in cytoskeletal structure to Rho have also begun to be delineated. Mechanical force generation by cells and simultaneous sensing of these physical forces play critical roles in vascular development by estimating whether individual cells will grow, differentiate, move or undergo apoptosis in the local tissue microenvironment. Future work in the vascular field therefore needs to incorporate physical control mechanisms into existing biochemical concepts of cell and tissue regulation.