Nrarp Coordinates Endothelial Notch and Wnt Signaling to Control Vessel Density in Angiogenesis

When and where to make or break new blood vessel connections is the key to understanding guided vascular patterning. VEGF-A stimulation and Dll4/Notch signaling cooperatively control the number of new connections by regulating endothelial tip cell formation. Here, we show that the Notch-regulated an...

Full description

Saved in:
Bibliographic Details
Published in:Developmental cell 2009-01, Vol.16 (1), p.70-82
Main Authors: Phng, Li-Kun, Potente, Michael, Leslie, Jonathan D., Babbage, Jane, Nyqvist, Daniel, Lobov, Ivan, Ondr, Jennifer K., Rao, Sujata, Lang, Richard A., Thurston, Gavin, Gerhardt, Holger
Format: Article
Language:English
Subjects:
Animals
beta Catenin - genetics
beta Catenin - metabolism
Biological and medical sciences
Blood Vessels - abnormalities
Blood Vessels - anatomy & histology
Blood Vessels - physiology
Cell differentiation, maturation, development, hematopoiesis
Cell physiology
DEVBIO
Endothelial Cells - metabolism
Female
Fundamental and applied biological sciences. Psychology
Intracellular Signaling Peptides and Proteins
Lymphoid Enhancer-Binding Factor 1 - genetics
Lymphoid Enhancer-Binding Factor 1 - metabolism
Mice
Molecular and cellular biology
Morphogenesis
Neovascularization, Physiologic - physiology
Proteins - genetics
Proteins - metabolism
Receptors, Notch - genetics
Receptors, Notch - metabolism
Retina - anatomy & histology
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Sialomucins - metabolism
Signal transduction
Signal Transduction - physiology
Transcription Factors - genetics
Transcription Factors - metabolism
Wnt Proteins - genetics
Wnt Proteins - metabolism
Zebrafish - anatomy & histology
Zebrafish - physiology
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:When and where to make or break new blood vessel connections is the key to understanding guided vascular patterning. VEGF-A stimulation and Dll4/Notch signaling cooperatively control the number of new connections by regulating endothelial tip cell formation. Here, we show that the Notch-regulated ankyrin repeat protein (Nrarp) acts as a molecular link between Notch- and Lef1-dependent Wnt signaling in endothelial cells to control stability of new vessel connections in mouse and zebrafish. Dll4/Notch-induced expression of Nrarp limits Notch signaling and promotes Wnt/Ctnnb1 signaling in endothelial stalk cells through interactions with Lef1. BATgal-reporter expression confirms Wnt signaling activity in endothelial stalk cells. Ex vivo, combined Wnt3a and Dll4 stimulation of endothelial cells enhances Wnt-reporter activity, which is abrogated by loss of Nrarp. In vivo, loss of Nrarp, Lef1, or endothelial Ctnnb1 causes vessel regression. We suggest that the balance between Notch and Wnt signaling determines whether to make or break new vessel connections.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2008.12.009