Notch expression patterns in the retina: An eye on receptor-ligand distribution during angiogenesis

The critical contribution of the Notch signaling pathway to vascular morphogenesis has been underscored by loss-of-function studies in mouse and zebrafish. Nonetheless, a comprehensive understanding as to how this signaling system influences the formation of blood vessels at the cellular and molecular level is far from reached. Here, we provide a detailed analysis of the distribution of active Notch1 in relation to its DSL (Delta, Serrate, Lag2) ligands, Jagged1, Delta-like1, and Delta-like4, during progressive stages of vascular morphogenesis and maturation. Important differences in the cellular distribution of Notch ligands were found. Jagged1 (Jag1) was detected in stalk cells of the leading vasculature and at arterial branch points, a site where Delta-like4 (D114) was clearly absent. D114 was the only ligand expressed in tip cells at the end of the growing vascular sprouts. It was also present in stalk cells, capillaries, arterial endothelium, and in mural cells of mature arteries in a homogenous manner. Delta-like 1 (D111) was observed in both arteries and veins of the developing network, but was also excluded from mature arterial branch points. These findings support alternative and distinct roles for Notch ligands (luring the angiogenic process. (c) 2006 Elsevier B.V. All rights reserved.