PUBLICATION

The netrin receptor UNC5B promotes angiogenesis in specific vascular beds

Authors
Navankasattusas, S., Whitehead, K.J., Suli, A., Sorensen, L.K., Lim, A.H., Zhao, J., Park, K.W., Wythe, J.D., Thomas, K.R., Chien, C.B., and Li, D.Y.
ID
ZDB-PUB-080226-21
Date
2008
Source
Development (Cambridge, England)   135(4): 659-667 (Journal)
Registered Authors
Chien, Chi-Bin, Lim, Amy, Suli, Arminda, Wythe, Joshua
Keywords
Angiogenesis, Netrin, Placenta, UNC5B, Zebrafish, Mouse
MeSH Terms
  • Animals
  • Arterioles/abnormalities
  • Arterioles/pathology
  • Blood Vessels/embryology*
  • Blood Vessels/metabolism
  • Embryo Loss
  • Embryo, Mammalian/abnormalities
  • Embryo, Mammalian/blood supply
  • Embryo, Mammalian/pathology
  • Embryo, Nonmammalian/cytology
  • Endothelium/embryology
  • Female
  • Gene Expression Regulation, Developmental
  • Hypoxia
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic*
  • Organ Specificity
  • Phenotype
  • Placenta/metabolism
  • Receptors, Cell Surface/deficiency
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/metabolism*
  • Regional Blood Flow
  • Signal Transduction
  • Umbilical Cord/blood supply
  • Zebrafish/embryology
PubMed
18223200 Full text @ Development
Abstract
There is emerging evidence that the canonical neural guidance factor netrin can also direct the growth of blood vessels. We deleted the gene encoding UNC5B, a receptor for the netrin family of guidance molecules, specifically within the embryonic endothelium of mice. The result is a profound structural and functional deficiency in the arterioles of the placental labyrinth, which leads first to flow reversal in the umbilical artery and ultimately to embryonic death. As this is the only detectable site of vascular abnormality in the mutant embryos, and because the phenotype cannot be rescued by a wild-type trophectoderm, we propose that UNC5B-mediated signaling is a specific and autonomous component of fetal-placental angiogenesis. Disruption of UNC5B represents a unique example of a mutation that acts solely within the fetal-placental vasculature and one that faithfully recapitulates the structural and physiological characteristics of clinical uteroplacental insufficiency. This pro-angiogenic, but spatially restricted requirement for UNC5B is not unique to murine development, as the knock-down of the Unc5b ortholog in zebrafish similarly results in the specific and highly penetrant absence of the parachordal vessel, the precursor to the lymphatic system.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes