Elsevier

Developmental Biology

Volume 425, Issue 2, 15 May 2017, Pages 101-108
Developmental Biology

Short Communication
CNS angiogenesis and barriergenesis occur simultaneously

https://doi.org/10.1016/j.ydbio.2017.03.017Get rights and content
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Highlights

  • Zebrafish glut1b:mCherry serves as an in vivo reporter of blood-brain barriergenesis.

  • Live imaging reveals that CNS angiogenesis and barriergenesis occur simultaneously.

  • Forward genetic screen using glut1b:mCherry identifies a zebrafish gpr124 mutant.

  • Zebrafish plvap:EGFP is an in vivo indicator of blood-brain barrier maturation.

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.

Keywords

Blood-brain barrier (BBB)
Brain endothelial cell (BEC)
Barriergenesis
Angiogenesis
Glucose transporter 1 (Glut1)
Plasmalemma vesicle-associated protein (Plvap)

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