Netrin-1 inhibits sprouting angiogenesis in developing avian embryos.
Netrin-1 is a bifunctional axonal guidance cue, capable of attracting or repelling developing axons via activation of receptors of the deleted in colorectal cancer (DCC) and uncoordinated 5 (UNC5) families, respectively. In addition to its role in axon guidance, Netrin-1 has been implicated in angiogenesis, where it may also act as a bifunctional cue. Attractive effects of Netrin-1 on endothelial cells appear to be mediated by an as yet unknown receptor, while repulsion of developing blood vessels in mouse embryos is mediated by the UNC5B receptor. To explore evolutionary conservation of vascular UNC5B expression and function, we have cloned the chick unc5b homologue. Chick and quail embryos showed unc5b expression in arterial EC and sprouting angiogenic capillaries. To test if Netrin-1 displayed pro- or anti-angiogenic activities in the avian embryo, we grafted cell lines expressing recombinant chick or human Netrin-1 at different stages of development. Netrin-1 expressing cells inhibited angiogenic sprouting of unc5b expressing blood vessels, but had no pro-angiogenic activity at any stage of development examined. Netrin-1 also had no effect on the recruitment of circulating endothelial precursor cells. Taken together, these data indicate that vascular unc5b expression and function is conserved between chick and mice.
Bouvrée
Karine
K
Inserm, U833, F-75005 Paris, France; Collège de France, 11, Place Marcelin Berthelot, F-75005 Paris, France.
Larrivée
Bruno
B
Lv
Xiang
X
Yuan
Li
L
DeLafarge
Benjamin
B
Freitas
Catarina
C
Mathivet
Thomas
T
Bréant
Christiane
C
Tessier-Lavigne
Marc
M
Bikfalvi
Andreas
A
Eichmann
Anne
A
Pardanaud
Luc
L
D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075386:Netrin Receptors; D000075388:Netrin-1; D011784:Quail / Q000196:embryology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617353:Ntn1 protein, mouse; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000075388:Netrin-1