The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis.
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IF: 66.850
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Cited by: 713
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Abstract

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.

Keywords

Spatial Gene Expression
PROCEDURE

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Blood Vessels
Calcium-Binding Proteins
Embryo, Mammalian
Endothelial Cells
Endothelium, Vascular
Female
Intercellular Signaling Peptides and Proteins
Intracellular Signaling Peptides and Proteins
Jagged-1 Protein
Male
Membrane Proteins
Mice
Mice, Transgenic
Mutation
Neovascularization, Physiologic
Receptors, Notch
Retina
Serrate-Jagged Proteins

Authors

Benedito, Rui
Roca, Cristina
Sörensen, Inga
Adams, Susanne
Gossler, Achim
Fruttiger, Marcus
Adams, Ralf H

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