The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system.
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.
Lu
Xiaowei
X
Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
Le Noble
Ferdinand
F
Yuan
Li
L
Jiang
Quingjan
Q
De Lafarge
Benjamin
B
Sugiyama
Daisuke
D
Bréant
Christiane
C
Claes
Filip
F
De Smet
Frederik
F
Thomas
Jean-Léon
JL
Autiero
Monica
M
Carmeliet
Peter
P
Tessier-Lavigne
Marc
M
Eichmann
Anne
A
D000818:Animals; D001808:Blood Vessels / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009154:Mutation / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D000075386:Netrin Receptors; D000075388:Netrin-1; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins
D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617353:Ntn1 protein, mouse; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; C000617355:ntn1a protein, zebrafish; D000075388:Netrin-1