PMID- 19524514 OWN - NLM STAT- MEDLINE VI - 137 IP - 6 TI - The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. PG - 1124-35 LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cell JT - Cell JID - 0413066 IS - 1097-4172 (Electronic) LID - 10.1016/j.cell.2009.03.025 [doi] FAU - Benedito, Rui AU - Benedito R AD - Cancer Research UK London Research Institute, Vascular Development Laboratory, London, UK. FAU - Roca, Cristina AU - Roca C FAU - Sörensen, Inga AU - Sörensen I FAU - Adams, Susanne AU - Adams S FAU - Gossler, Achim AU - Gossler A FAU - Fruttiger, Marcus AU - Fruttiger M FAU - Adams, Ralf H AU - Adams RH IS - 0092-8674 (Linking) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Calcium-Binding Proteins) RN - 0 (DLL4 protein, mouse) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Jag1 protein, mouse) RN - 0 (Jagged-1 Protein) RN - 0 (Membrane Proteins) RN - 0 (Receptors, Notch) RN - 0 (Serrate-Jagged Proteins) SB - IM MH - Adaptor Proteins, Signal Transducing MH - Animals MH - Blood Vessels/cytology/*embryology MH - Calcium-Binding Proteins/genetics/*metabolism MH - Embryo, Mammalian/metabolism MH - Endothelial Cells/metabolism MH - Endothelium, Vascular/metabolism MH - Female MH - Intercellular Signaling Peptides and Proteins/genetics/*metabolism MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Jagged-1 Protein MH - Male MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Mice, Transgenic MH - Mutation MH - *Neovascularization, Physiologic MH - Receptors, Notch/metabolism MH - Retina/embryology MH - Serrate-Jagged Proteins DCOM- 20090713 LR - 20211028 DP - 2009 Jun 12 AB - The Notch pathway is a highly conserved signaling system that controls a diversity of growth, differentiation, and patterning processes. In growing blood vessels, sprouting of endothelial tip cells is inhibited by Notch signaling, which is activated by binding of the Notch receptor to its ligand Delta-like 4 (Dll4). Here, we show that the Notch ligand Jagged1 is a potent proangiogenic regulator in mice that antagonizes Dll4-Notch signaling in cells expressing Fringe family glycosyltransferases. Upon glycosylation of Notch, Dll4-Notch signaling is enhanced, whereas Jagged1 has weak signaling capacity and competes with Dll4. Our findings establish that the equilibrium between two Notch ligands with distinct spatial expression patterns and opposing functional roles regulates angiogenesis, a mechanism that might also apply to other Notch-controlled biological processes.