Speaker: Saulius Sumanas, professor in the University of South Florida Department of Pathology and Cell Biology, USC Health Heart Institute and Morsani College of Medicine

Title: "Molecular mechanisms regulating blood vessel development and disease"

Abstract: Vascular endothelial cells (ECs) form endothelial lining of all blood vessels and play critical roles in maintaining vascular integrity and in repairing injured or ischemic tissues. However, the mechanisms involved in vascular development and regeneration are still incompletely understood. We are using zebrafish as a model system to study molecular mechanisms involved in vascular development. Our previous research has identified an evolutionarily conserved ETS transcription factor Etv2 / Etsrp, which functions as a master regulator of vasculogenesis. Etv2 function is required for the initial differentiation of vascular endothelial cells during embryonic vasculogenesis. More recently, we have identified a population of late-forming endothelial progenitor cells in zebrafish embryos (termed secondary vascular field, SVF), which emerge after 24 hpf stage, when blood circulation has been initiated, and show strong Etv2 expression. We demonstrate that SVF cells can uniquely incorporate into the functional vasculature. We have further investigated the molecular mechanisms that govern the emergence of these SVF cells and their contribution to vasculature. We identified that the Junctional Adhesion Molecule Jam2b is expressed in the SVF-forming region and is required for the emergence of SVF cells in zebrafish embryos. Time-lapse imaging and jam2b:Cre based lineage tracing showed that SVF cells serve as the major source of intestinal vasculature, which are subsequently remodeled to provide the blood flow to many internal organs. To analyze the functional role of Jam2b and a related Jam2a gene in vascular development, we generated double maternal-zygotic jam2a; jam2b mutants, which display a greatly reduced number of Etv2-positive SVF cells and show defects in the intestinal vasculature development. In summary, our results identify new roles for Jam2 signaling in the emergence organ-specific vascular progenitors. These results will be important to understand the mechanisms that regulate vascular development and promote the development of strategies aimed at vascular regeneration.

Hosts: Clyde Campbell, assistant professor in genetics, development and cell biology (GDCB), and Raquel Espin Palazon, GDCB assistant professor