Death Receptors DR6 and TROY Regulate Brain Vascular Development
- Authors
- Tam, S.J., Richmond, D.L., Kaminker, J.S., Modrusan, Z., Martin-McNulty, B., Cao, T.C., Weimer, R.M., Carano, R.A., van Bruggen, N., and Watts, R.J.
- ID
- ZDB-PUB-120223-2
- Date
- 2012
- Source
- Developmental Cell 22(2): 403-417 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Biomarkers/metabolism
- Blood-Brain Barrier/metabolism*
- Blotting, Western
- Cell Communication
- Cells, Cultured
- Central Nervous System/blood supply*
- Central Nervous System/metabolism*
- Embryo, Mammalian/cytology
- Embryo, Mammalian/metabolism
- Endothelium, Vascular/cytology
- Endothelium, Vascular/metabolism
- Gene Expression Profiling
- Gene Expression Regulation, Developmental
- Humans
- Immunoprecipitation
- MAP Kinase Kinase 4/antagonists & inhibitors
- MAP Kinase Kinase 4/genetics
- MAP Kinase Kinase 4/metabolism
- Mice
- Neovascularization, Physiologic*
- Oligonucleotide Array Sequence Analysis
- RNA, Messenger/genetics
- RNA, Small Interfering/genetics
- Real-Time Polymerase Chain Reaction
- Receptors, Tumor Necrosis Factor/genetics
- Receptors, Tumor Necrosis Factor/metabolism*
- Signal Transduction
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Zebrafish/growth & development
- Zebrafish/metabolism
- beta Catenin/genetics
- beta Catenin/metabolism
- PubMed
- 22340501 Full text @ Dev. Cell
Signaling events that regulate central nervous system (CNS) angiogenesis and blood-brain barrier (BBB) formation are only beginning to be elucidated. By evaluating the gene expression profile of mouse vasculature, we identified DR6/TNFRSF21 and TROY/TNFRSF19 as regulators of CNS-specific angiogenesis in both zebrafish and mice. Furthermore, these two death receptors interact both genetically and physically and are required for vascular endothelial growth factor (VEGF)-mediated JNK activation and subsequent human brain endothelial sprouting in vitro. Increasing beta-catenin levels in brain endothelium upregulate DR6 and TROY, indicating that these death receptors are downstream target genes of Wnt/beta-catenin signaling, which has been shown to be required for BBB development. These findings define a role for death receptors DR6 and TROY in CNS-specific vascular development.