PUBLICATION
CNS angiogenesis and barriergenesis occur simultaneously
- Authors
- Umans, R.A., Henson, H.E., Mu, F., Parupalli, C., Ju, B., Peters, J.L., Lanham, K.A., Plavicki, J.S., Taylor, M.R.
- ID
- ZDB-PUB-170404-17
- Date
- 2017
- Source
- Developmental Biology 425(2): 101-108 (Journal)
- Registered Authors
- Ju, Bensheng, Plavicki, Jessica, Taylor, Michael R.
- Keywords
- Angiogenesis, Barriergenesis, Blood-brain barrier (BBB), Brain endothelial cell (BEC), Glucose transporter 1 (Glut1), Plasmalemma vesicle-associated protein (Plvap)
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Blood-Brain Barrier/physiology*
- Cell Differentiation
- Endothelial Cells/metabolism
- Genes, Reporter
- Genetic Testing
- Green Fluorescent Proteins/metabolism
- Mutation/genetics
- Neovascularization, Physiologic*
- Promoter Regions, Genetic/genetics
- Receptors, G-Protein-Coupled/genetics
- Zebrafish/physiology*
- Zebrafish Proteins/genetics
- PubMed
- 28365243 Full text @ Dev. Biol.
Citation
Umans, R.A., Henson, H.E., Mu, F., Parupalli, C., Ju, B., Peters, J.L., Lanham, K.A., Plavicki, J.S., Taylor, M.R. (2017) CNS angiogenesis and barriergenesis occur simultaneously. Developmental Biology. 425(2):101-108.
Abstract
The blood-brain barrier (BBB) plays a vital role in the central nervous system (CNS). A comprehensive understanding of BBB development has been hampered by difficulties in observing the differentiation of brain endothelial cells (BECs) in real-time. Here, we generated two transgenic zebrafish line, Tg(glut1b:mCherry) and Tg(plvap:EGFP), to serve as in vivo reporters of BBB development. We showed that barriergenesis (i.e. the induction of BEC differentiation) occurs immediately as endothelial tips cells migrate into the brain parenchyma. Using the Tg(glut1b:mCherry) transgenic line, we performed a genetic screen and identified a zebrafish mutant with a nonsense mutation in gpr124, a gene known to play a role in CNS angiogenesis and BBB development. We also showed that our transgenic plvap:EGFP line, a reporter of immature brain endothelium, is initially expressed in newly formed brain endothelial cells, but subsides during BBB maturation. Our results demonstrate the ability to visualize the in vivo differentiation of brain endothelial cells into the BBB phenotype and establish that CNS angiogenesis and barriergenesis occur simultaneously.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping