PUBLICATION

Notch3 establishes brain vascular integrity by regulating pericyte number

Authors
Wang, Y., Pan, L., Moens, C.B., and Appel, B.
ID
ZDB-PUB-140127-7
Date
2014
Source
Development (Cambridge, England)   141(2): 307-317 (Journal)
Registered Authors
Appel, Bruce, Moens, Cecilia, Pan, Luyuan
Keywords
Blood-brain barrier, Intraventricular hemorrhage, Notch3, Pericytes, Vasculature
MeSH Terms
  • Receptor, Platelet-Derived Growth Factor beta/genetics
  • Receptor, Platelet-Derived Growth Factor beta/metabolism
  • Cell Count
  • Brain/blood supply
  • Brain/growth & development*
  • Brain/metabolism*
  • Humans
  • Gene Expression Regulation, Developmental
  • Cerebral Hemorrhage/etiology
  • Cerebral Hemorrhage/genetics
  • Cerebral Hemorrhage/metabolism
  • Cell Differentiation
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Signal Transduction
  • Cell Proliferation
  • Receptors, Notch/deficiency
  • Receptors, Notch/genetics
  • Receptors, Notch/metabolism*
  • Animals, Genetically Modified
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism*
  • Animals
  • Blood-Brain Barrier/growth & development
  • Blood-Brain Barrier/metabolism
  • Pericytes/cytology*
  • Pericytes/metabolism*
  • Mutation
(all 30)
PubMed
24306108 Full text @ Development
Abstract

Brain pericytes are important regulators of brain vascular integrity, permeability and blood flow. Deficiencies of brain pericytes are associated with neonatal intracranial hemorrhage in human fetuses, as well as stroke and neurodegeneration in adults. Despite the important functions of brain pericytes, the mechanisms underlying their development are not well understood and little is known about how pericyte density is regulated across the brain. The Notch signaling pathway has been implicated in pericyte development, but its exact roles remain ill defined. Here, we report an investigation of the Notch3 receptor using zebrafish as a model system. We show that zebrafish brain pericytes express notch3 and that notch3 mutant zebrafish have a deficit of brain pericytes and impaired blood-brain barrier function. Conditional loss- and gain-of-function experiments provide evidence that Notch3 signaling positively regulates brain pericyte proliferation. These findings establish a new role for Notch signaling in brain vascular development whereby Notch3 signaling promotes expansion of the brain pericyte population.

Genes / Markers
Figures
Figure Gallery (15 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
foxd3MO2-foxd3MRPHLNO
foxd3MO3-foxd3MRPHLNO
notch3MO1-notch3MRPHLNO
1 - 3 of 3
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Fish
Antibodies
Orthology
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
mCherryEFGmCherry
1 - 2 of 2
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Mapping
No data available