Abstract
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.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain / blood supply
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Calcium-Binding Proteins
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Capillaries / cytology*
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Capillaries / physiology*
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Cell Differentiation / physiology
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Cerebrovascular Circulation
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Endothelium, Vascular / cytology*
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Endothelium, Vascular / physiology*
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Intercellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Membrane Proteins
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Mice
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Morphogenesis / physiology
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Neovascularization, Physiologic
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Proteins / physiology*
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Proto-Oncogene Proteins / physiology*
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Rats
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Receptor, Notch4
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Receptors, Cell Surface*
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Receptors, Notch
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Serrate-Jagged Proteins
Substances
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Calcium-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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JAG1 protein, human
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Jag1 protein, mouse
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Jag1 protein, rat
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Jagged-1 Protein
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Membrane Proteins
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NOTCH4 protein, human
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Proteins
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Proto-Oncogene Proteins
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Receptor, Notch4
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Receptors, Cell Surface
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Receptors, Notch
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Serrate-Jagged Proteins