Please use this identifier to cite or link to this item: https://doi.org/10.1242/dev.049015
Title: Von Hippel-Lindau protein regulates transition from the fetal to the adult circulatory system in retina
Authors: Kurihara, T
Kubota, Y
Ozawa, Y
Takubo, K
Noda, K
Simon, M.C
Johnson, R.S
Suematsu, M
Tsubota, K
Ishida, S
Goda, N
Suda, T 
Okano, H
Keywords: oxygen
ubiquitin protein ligase E3
von Hippel Lindau protein
hypoxia inducible factor 1alpha
vasculotropin A
animal experiment
animal model
animal tissue
article
cardiovascular system
controlled study
disease course
down regulation
nonhuman
oxygen sensing
priority journal
protein expression
retina
retina blood vessel
retina degeneration
retina development
animal
blood vessel
C57BL mouse
confocal microscopy
cytology
gene expression regulation
genetics
growth, development and aging
immunohistochemistry
in situ hybridization
macrophage
metabolism
mouse
pathology
physiology
retina
reverse transcription polymerase chain reaction
Mus
Animals
Blood Vessels
Gene Expression Regulation, Developmental
Hypoxia-Inducible Factor 1, alpha Subunit
Immunohistochemistry
In Situ Hybridization
Macrophages
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Retina
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A
Von Hippel-Lindau Tumor Suppressor Protein
Issue Date: 2010
Citation: Kurihara, T, Kubota, Y, Ozawa, Y, Takubo, K, Noda, K, Simon, M.C, Johnson, R.S, Suematsu, M, Tsubota, K, Ishida, S, Goda, N, Suda, T, Okano, H (2010). Von Hippel-Lindau protein regulates transition from the fetal to the adult circulatory system in retina. Development 137 (9) : 1563-1571. ScholarBank@NUS Repository. https://doi.org/10.1242/dev.049015
Rights: Attribution 4.0 International
Abstract: In early neonates, the fetal circulatory system undergoes dramatic transition to the adult circulatory system. Normally, embryonic connecting vessels, such as the ductus arteriosus and the foramen ovale, close and regress. In the neonatal retina, hyaloid vessels maintaining blood flow in the embryonic retina regress, and retinal vessels take over to form the adult-type circulatory system. This process is regulated by a programmed cell death switch mediated by macrophages via Wnt and angiopoietin 2 pathways. In this study, we seek other mechanisms that regulate this process, and focus on the dramatic change in oxygen environment at the point of birth. The von Hippel-Lindau tumor suppressor protein (pVHL) is a substrate recognition component of an E3-ubiquitin ligase that rapidly destabilizes hypoxia-inducible factor as (HIF-?s) under normoxic, but not hypoxic, conditions. To examine the role of oxygen-sensing mechanisms in retinal circulatory system transition, we generated retina-specific conditional-knockout mice for VHL (Vhl ?-CreKO mice). These mice exhibit arrested transition from the fetal to the adult circulatory system, persistence of hyaloid vessels and poorly formed retinal vessels. These defects are suppressed by intraocular injection of FLT1-Fc protein [a vascular endothelial growth factor (VEGF) receptor-1 (FLT1)/Fc chimeric protein that can bind VEGF and inhibit its activity], or by inactivating the HIF-1a gene. Our results suggest that not only macrophages but also tissue oxygen-sensing mechanisms regulate the transition from the fetal to the adult circulatory system in the retina. © 2010. Published by The Company of Biologists Ltd.
Source Title: Development
URI: https://scholarbank.nus.edu.sg/handle/10635/180991
ISSN: 0950-1991
DOI: 10.1242/dev.049015
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1242_dev_049015.pdf2.54 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons