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 (Dll4) was clearly absent. Dll4 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-like1 (Dll1) 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 during the angiogenic process.
Hofmann
Jennifer J
JJ
Molecular Biology Institute, Boyer Hall 559, 611 Charles Young Drive East, UCLA, Los Angeles, CA 90095, USA.
Luisa Iruela-Arispe
M
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D018919:Neovascularization, Physiologic; D051881:Receptor, Notch1 / Q000096:biosynthesis / Q000235:genetics*; D012160:Retina / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D012171:Retinal Vessels / Q000166:cytology / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; C511877:Dll3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D029961:Zebrafish Proteins; C000606276:jag1a protein, zebrafish