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Early Unguided Human Brain Organoid Neurovascular Niche Modeling into the Permissive Chick Embryo Chorioallantoic Membrane
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Death receptors DR6 and TROY regulate brain vascular development.

Stephen J Tam1, David L Richmond, Joshua S Kaminker

  • 1Neurodegeneration Labs, Department of Neuroscience, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.

Developmental Cell
|February 21, 2012
PubMed
Summary

Death receptors DR6 and TROY regulate central nervous system (CNS) angiogenesis and blood-brain barrier (BBB) development. These receptors are downstream targets of Wnt/beta-catenin signaling, crucial for CNS vascularization.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Vascular Biology

Background:

  • Central nervous system (CNS) angiogenesis and blood-brain barrier (BBB) formation are complex processes involving intricate signaling pathways.
  • Understanding the molecular mechanisms regulating CNS vascular development is crucial for addressing neurological disorders.

Purpose of the Study:

  • To identify novel regulators of CNS-specific angiogenesis and blood-brain barrier (BBB) formation.
  • To elucidate the role of death receptors DR6 (TNFRSF21) and TROY (TNFRSF19) in CNS vascular development.

Main Methods:

  • Gene expression profiling of mouse vasculature.
  • Functional studies in zebrafish and mice models.
  • In vitro assays using human brain endothelial cells.
  • Analysis of Wnt/beta-catenin signaling pathway interactions.

Main Results:

  • DR6 and TROY were identified as key regulators of CNS-specific angiogenesis in both zebrafish and mice.
  • DR6 and TROY physically and genetically interact and are essential for VEGF-mediated JNK activation.
  • DR6 and TROY are downstream targets of Wnt/beta-catenin signaling in brain endothelium.
  • Upregulation of DR6 and TROY is linked to increased beta-catenin levels.

Conclusions:

  • Death receptors DR6 and TROY play a critical role in CNS-specific vascular development.
  • These findings reveal a novel link between death receptor signaling and Wnt/beta-catenin pathway in BBB formation.
  • DR6 and TROY represent potential therapeutic targets for modulating CNS angiogenesis and BBB integrity.