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Related Experiment Videos

CNS angiogenesis and barriergenesis occur simultaneously.

Robyn A Umans1, Hannah E Henson1, Fangzhou Mu2

  • 1Department of Chemical Biology & Therapeutics, St. Jude Children's Research Hospital, Memphis, TN, USA; Integrated Program in Biomedical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA.

Developmental Biology
|April 3, 2017
PubMed
Summary

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Researchers visualized blood-brain barrier (BBB) development in real-time using zebrafish. They discovered that central nervous system (CNS) angiogenesis and barriergenesis occur simultaneously, identifying a key gene involved in this process.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • The blood-brain barrier (BBB) is crucial for central nervous system (CNS) function.
  • Observing brain endothelial cell (BEC) differentiation during BBB development in real-time has been challenging.

Purpose of the Study:

  • To develop in vivo reporters for visualizing BBB development.
  • To investigate the timing of BBB formation and CNS angiogenesis.
  • To identify genetic factors influencing BBB development.

Main Methods:

  • Generated transgenic zebrafish lines (Tg(glut1b:mCherry) and Tg(plvap:EGFP)) as BBB reporters.
  • Utilized a genetic screen with Tg(glut1b:mCherry) to identify mutants.
  • Observed BEC differentiation and BBB maturation in vivo.
Keywords:
AngiogenesisBarriergenesisBlood-brain barrier (BBB)Brain endothelial cell (BEC)Glucose transporter 1 (Glut1)Plasmalemma vesicle-associated protein (Plvap)

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Main Results:

  • Barriergenesis, the induction of BEC differentiation, occurs concurrently with endothelial tip cell migration into the brain.
  • Identified a zebrafish mutant with a gpr124 gene mutation, highlighting its role in CNS angiogenesis and BBB development.
  • The Tg(plvap:EGFP) reporter showed expression in immature brain endothelium, decreasing as the BBB matures.

Conclusions:

  • The study successfully visualized in vivo BEC differentiation into the BBB phenotype.
  • CNS angiogenesis and barriergenesis are simultaneous processes.
  • gpr124 is a key gene involved in CNS angiogenesis and BBB formation.