Vascular expression of Notch pathway receptors and ligands is restricted to arterial vessels.
Mice with targeted mutations in genes required for Notch signal transduction die during embryogenesis, displaying overt signs of hemorrhage due to defects in their vascular development. Surprisingly, directed expression of a constitutively active form of Notch4 within mouse endothelial cells produces a similar vascular embryonic lethality. Moreover, patients with mutations in Notch3 exhibit the cerebral vascular disorder, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). These findings underscore the importance of Notch signaling in vascular development; however, they do not identify the specific functional defect. Here, we report that Notch1, Notch3, Notch4, Delta4, Jagged1 and Jagged2 are all expressed in arteries, but are not expressed by veins. These findings identify an aspect of Notch signaling that could contribute to the mechanism by which this pathway modulates vascular morphogenesis.
Villa
N
N
Department of Biological Chemistry, UCLA, Los Angeles, CA 90095-1737, USA.
Walker
L
L
Lindsell
C E
CE
Gasson
J
J
Iruela-Arispe
M L
ML
Weinmaster
G
G
D000818:Animals; D001158:Arteries / Q000002:abnormalities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D009154:Mutation; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology*; D051880:Receptors, Notch; D015398:Signal Transduction
D008024:Ligands; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D051880:Receptors, Notch