The orphan nuclear receptor COUP-TFII is required for angiogenesis and heart development

The embryonic expression of COUP-TFII, an orphan nuclear receptor, suggests that it may participate in mesenchymal-epithelial interactions required fo r organogenesis. Targeted deletion of the COUP-TFII gene results in embryon ic lethality with defects in angiogenesis and heart development. COUP-TFII mutants are defective in remodeling the primitive capillary plexus into lar ge and small microcapillaries. In the COUP-TFII mutant heart, the atria and sinus venosus fail to develop past the primitive tube stage. Reciprocal in teractions between the endothelium and the mesenchyme in the vascular syste m and heart are essential for normal development of these systems. In fact, the expression of Angiopoietin-1, a proangiogenic soluble factor thought t o mediate the mesenchymal-endothelial interactions during heart development and vascular remodeling, is down-regulated in COUP-TFII mutants. This down -regulation suggests that COUP-TFII may be required for bidirectional signa ling between the endothelial and mesenchymal compartments essential for pro per angiogenesis and heart development.