Fig. 8. Coronary arteries and veins represent distinct vascular lineages. (A) H&E stained section of an E12.5 heart, demonstrating that coronary veins (black arrowhead) contain both red blood cells and rosettes of undefined cells (white arrow), whereas coronary arteries (black arrow) contain only red blood cells. (B) High magnification of the outlined area in A. (C-E) Immunofluorescent staining of E12.5 hearts demonstrating that although both coronary veins (C, arrowhead) and coronary arteries (C, arrow) express PECAM, only coronary veins express CD45 (D, arrowhead) and SCA1 (E, arrowhead). Cells located within coronary veins express CD45 (D, arrow) indicating that they are of hematopoietic origin. Blue, PECAM; green, CD45; Red, SCA1. (F-H) Immunofluorescent staining of SCL/TAL1-CD4 knock-in E12.5 hearts, demonstrating that SCL/TAL1 is expressed in coronary veins (arrowhead) but not in coronary arteries (arrow). Red, PECAM; green, CD4 (SCL/TAL1). H, merge of fluorescent signals in F,G. (C-G) Immunofluorescent signals are superimposed on DIC images. (A,C-H) Taken at 400x magnification. (I) The developing coronary vascular plexus is composed of two distinct subsets of blood vessels: coronary arteries and veins. (J) Model describing the origins of the coronary arterial and venous lineages. Coronary veins are derived from hemangioblasts, whereas coronary arteries are probably derived from endothelial cells. (K) Model describing the signaling events that coordinately control coronary artery and vein development. Perivascular HH signaling controls coronary artery growth by regulating perivascular expression of VEGFA, VEGFB and VEGFC. Myocardial HH signaling controls myocardial VEGFA and VEGFB expression, which is required for coronary vein growth, and in combination with perivascular VEGF expression, positively regulates coronary artery growth.