The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system

Xiaowei Lu; Ferdinand Le Noble; Li Yuan; Quingjan Jiang; Benjamin De Lafarge; Daisuke Sugiyama; Christiane Bréant; Filip Claes; Frederik De Smet; Jean-Léon Thomas; Monica Autiero; Peter Carmeliet; Marc Tessier-Lavigne; Anne Eichmann

doi:10.1038/nature03080

The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system

Nature. 2004 Nov 11;432(7014):179-86. doi: 10.1038/nature03080. Epub 2004 Oct 27.

Authors

Xiaowei Lu¹, Ferdinand Le Noble, Li Yuan, Quingjan Jiang, Benjamin De Lafarge, Daisuke Sugiyama, Christiane Bréant, Filip Claes, Frederik De Smet, Jean-Léon Thomas, Monica Autiero, Peter Carmeliet, Marc Tessier-Lavigne, Anne Eichmann

Affiliation

¹ Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.

PMID: 15510105
DOI: 10.1038/nature03080

Abstract

Blood vessels and nerves are complex, branched structures that share a high degree of anatomical similarity. Guidance of vessels and nerves has to be exquisitely regulated to ensure proper wiring of both systems. Several regulators of axon guidance have been identified and some of these are also expressed in endothelial cells; however, the extent to which their guidance functions are conserved in the vascular system is still incompletely understood. We show here that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin-1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia, excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Blood Vessels / abnormalities
Blood Vessels / cytology
Blood Vessels / embryology*
Blood Vessels / metabolism*
Cell Movement / drug effects
Cell Size / drug effects
Endothelial Cells / cytology
Endothelial Cells / drug effects
Endothelial Cells / metabolism
Endothelium, Vascular / cytology
Endothelium, Vascular / drug effects
Endothelium, Vascular / metabolism
Mice
Molecular Sequence Data
Morphogenesis*
Mutation / genetics
Nerve Growth Factors / genetics
Nerve Growth Factors / metabolism
Nerve Growth Factors / pharmacology
Netrin Receptors
Netrin-1
Pseudopodia / drug effects
Pseudopodia / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Cell Surface / genetics
Receptors, Cell Surface / metabolism*
Tumor Suppressor Proteins
Zebrafish / embryology
Zebrafish / genetics
Zebrafish / metabolism
Zebrafish Proteins

Substances

Nerve Growth Factors
Netrin Receptors
Ntn1 protein, mouse
RNA, Messenger
Receptors, Cell Surface
Tumor Suppressor Proteins
Zebrafish Proteins
ntn1a protein, zebrafish
Netrin-1

Associated data

GENBANK/AY764274