Notch4 and Jagged-1 induce microvessel differentiation of rat brain endothelial cells.
The mouse Notch4 gene is expressed specifically in endothelial cells. Notch4/int-3, a truncated form of Notch4, acts as a constitutive activated Notch receptor. We used rat brain microvessel endothelial cells (RBE4) to study the role of Notch4 and Jagged-1 in endothelial cell differentiation. Both Notch4/int-3 and Jagged-1 were able to induce microvessel-like structures with morphological and biochemical properties similar to brain endothelial microvessels. Ectopic expression of full-length Notch4 did not effect RBE4 cells. Activation of the Notch signal transduction pathway was measured by the induction of endogenous Notch4 and Jagged-1 genes and of Jagged-1 proteins. The observed morphological changes to RBE4 cells correlated with endogenous Notch4 and Jagged-1 gene activation. Our observations demonstrate that Notch signaling can promote endothelial cell differentiation and morphogenesis.
Uyttendaele
H
H
Department of Pathology and OB/GYN, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, New York, 10032, USA.
Closson
V
V
Wu
G
G
Roux
F
F
Weinmaster
G
G
Kitajewski
J
J
D000818:Animals; D001921:Brain / Q000098:blood supply; D002135:Calcium-Binding Proteins; D002196:Capillaries / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051379:Mice; D009024:Morphogenesis / Q000502:physiology; D018919:Neovascularization, Physiologic; D011506:Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C106075:NOTCH4 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins