Article

Suppression of Notch signalling by the COUP-TFII transcription factor regulates vein identity.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nature (impact factor: 36.28). 06/2005; 435(7038):98-104. DOI:10.1038/nature03511 pp.98-104
Source: PubMed

ABSTRACT Arteries and veins are anatomically, functionally and molecularly distinct. The current model of arterial-venous identity proposes that binding of vascular endothelial growth factor to its heterodimeric receptor--Flk1 and neuropilin 1 (NP-1; also called Nrp1)--activates the Notch signalling pathway in the endothelium, causing induction of ephrin B2 expression and suppression of ephrin receptor B4 expression to establish arterial identity. Little is known about vein identity except that it involves ephrin receptor B4 expression, because Notch signalling is not activated in veins; an unresolved question is how vein identity is regulated. Here, we show that COUP-TFII (also known as Nr2f2), a member of the orphan nuclear receptor superfamily, is specifically expressed in venous but not arterial endothelium. Ablation of COUP-TFII in endothelial cells enables veins to acquire arterial characteristics, including the expression of arterial markers NP-1 and Notch signalling molecules, and the generation of haematopoietic cell clusters. Furthermore, ectopic expression of COUP-TFII in endothelial cells results in the fusion of veins and arteries in transgenic mouse embryos. Thus, COUP-TFII has a critical role in repressing Notch signalling to maintain vein identity, which suggests that vein identity is under genetic control and is not derived by a default pathway.

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Keywords

arterial characteristics
 
arterial endothelium
 
arterial identity
 
arterial markers NP-1
 
arterial-venous identity
 
current model
 
ectopic expression
 
endothelial cells enables veins
 
endothelial cells results
 
endothelium
 
ephrin receptor B4 expression
 
genetic control
 
molecularly distinct
 
neuropilin 1
 
Notch signalling molecules
 
orphan nuclear receptor superfamily
 
repressing Notch signalling
 
transgenic mouse embryos
 
unresolved question
 
vascular endothelial growth factor
 

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