Oxygen modifies artery differentiation and network morphogenesis in the retinal vasculature.
The mechanisms that control differentiation of immature blood vessels into either arteries or veins are not well understood. Because oxygen tension in arteries is higher than in veins, oxygen has the potential to be an instructive signal for artery/vein (AV) differentiation. We test this hypothesis by exposing newborn mice to moderate hypoxia (10% atmospheric oxygen) and studying AV differentiation in the developing retinal vasculature. Forming retinal arteries fail to express the artery-specific markers Delta-like 4 (Dll4) and EphrinB2 during hypoxia. However, other aspects of AV differentiation are retained such as high levels of alpha smooth muscle actin in arterial mural cells and vein-specific expression of the msr/apj gene. The capillary network between arteries and veins is denser, and capillaries expressing the venous marker msr/apj are found in territories normally occupied by arterial capillaries. Thus, it appears that high oxygen in arterial blood is required for arterial expression of Dll4 and EphrinB2, which could be involved in cell-cell repulsion pathways that dictate the normal segregation of arteries and veins.
Claxton
Suzanne
S
Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London, United Kingdom.
Fruttiger
Marcus
M
D000818:Animals; D000831:Animals, Newborn; D000075244:Apelin Receptors; D001272:Atmosphere / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects*; D042783:Endothelial Cells / Q000378:metabolism; D036388:Ephrin-B2 / Q000235:genetics / Q000378:metabolism; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D012161:Retinal Artery / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism
D000075244:Apelin Receptors; C491285:Aplnr protein, mouse; D036388:Ephrin-B2; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C064045:delta protein; D005287:Ferredoxin-NADP Reductase; D010100:Oxygen