| In order to overcome the limitations of diffusion, complex organisms depend on a circulatory system to deliver oxygen and nutrients and remove wastes from systemic tissues. Among the principal components of the circulatory system are the endothelial cells (ECs) which line the interior of the vasculature, effectively preventing circulating blood cells and proteins from interacting with surrounding tissues. Beyond their function as a barrier, however, ECs continuously remodel the vascular circuitry to provide tissues throughout the body with adequate access to the circulation. These dynamic processes take place during development and in the adult, and require that ECs react to various signals by modifying their behavior. Here, I report that the Bone Morphogenic Protein (BMP) signaling axis plays a significant role in the instruction of EC function. Furthermore, I present data that suggests that the extracellular matrix (ECM) protein Tenascin-C (TnC), may stimulate quiescent ECs to invade intravascular thrombi and promote neovascularization. Each of these topics will be addressed independently.;BMPs, which are members of the TGFbeta superfamily of diffusible growth factors, are important regulators of a number of cellular processes during development and in the adult. However, BMP's role during the initial formation of the vascular system has remained unclear. Here, I demonstrate that BMP antagonists inhibit the differentiation of ECs from mesodermal precursors in the avian embryo and suppress the ability of ECs to assemble into vascular networks. These findings suggest that the interplay between BMPs and their antagonists has a significant role in initial pattering of the embryonic vascular tree.;TnC is a large ECM protein, highly conserved in vertebrates. TnC null mice display no overt development phenotype and are viable (Saga, Yagi et al. 1992), however these animals have a decreased capacity to cope with injury (Koyama, Kusubata et al. 1998) and thrombosis (Ballard, Sharma et al. 2006). Here, I demonstrate that the interaction between ECs and TnC causes ECs to form multicellular clusters, and when these EC clusters are presented with a three dimensional fibrin matrix, they invade and rapidly form structures resembling vessels and capillary plexi. This data suggests that TnC may activate ECs in response to vascular insult. |
