April 12 2007
12:00 LSB 2320

Saulius Sumanas

How To Make a Blood Vessel: Insights From the Zebrafish


Blood vessel formation is critical during embryogenesis, carcinogenesis and tissue growth during wound repair and regeneration. Mechanisms controlling blood vessel formation de novo, vasculogenesis and blood vessel sprouting from the existing vessels, angiogenesis are still poorly understood. Zebrafish has recently emerged as a superior model system to study vasculogenesis and angiogenesis. In vertebrates, hematopoietic and vascular endothelial cells are thought to originate from a common precursor, hemangioblast. To identify novel genes that may be involved in vasculogenesis and/or angiogenesis I performed microarray analysis of the zebrafish cloche mutant embryos, defective in both hematopoietic and vascular endothelial cell formation. A novel ETS1-related protein Etsrp, encoding an ETS domain transcription factor, was among the multiple novel genes, identified during the microarray analysis. Etsrp embryonic expression is only restricted to the vascular endothelial cells and their earliest precursors. Morpholino knockdown of Etsrp protein function resulted in the complete absence of circulation in zebrafish embryos. In the absence of Etsrp function blood vessel progenitors, angioblasts, did not migrate, differentiate, or express any vascular markers. Overexpression of etsrp was sufficient to induce vasculogenesis in a variety of tissue types. These experiments argue that etsrp functions as a key regulatory gene in initiating vascular development. In addition, etsrp is required and sufficient for the formation of the myeloid lineage, apparently functioning at the hemangioblast level. The choice of endothelial versus myeloid fate depends on the combinatorial effect of etsrp, scl and alk8 signaling pathways.