PUBLICATION

Pituicyte Cues Regulate the Development of Permeable Neuro-Vascular Interfaces

Authors
Anbalagan, S., Gordon, L., Blechman, J., Matsuoka, R.L., Rajamannar, P., Wircer, E., Biran, J., Reuveny, A., Leshkowitz, D., Stainier, D.Y.R., Levkowitz, G.
ID
ZDB-PUB-181127-2
Date
2018
Source
Developmental Cell   47(6): 711-726.e5 (Journal)
Registered Authors
Anbalagan, Savani, Biran, Jacob, Blechman, Janna, Levkowitz, Gil, Matsuoka, Ryota, Rajamannar, Preethi, Reuveny, Adriana, Stainier, Didier, Wircer, Einav
Keywords
Claudin, arginine-vasopressin, astroglia, blood-brain barrier, fenestrae, microglia, neuroendocrine, neurovascular unit, oxytocin, pituicyte, plvap, tight junction, vascular permeability, zebrafish
Datasets
GEO:GSE106371
MeSH Terms
  • Animals
  • Claudin-5
  • Endothelium, Vascular/metabolism
  • Up-Regulation
  • Permeability
  • Blood-Brain Barrier/metabolism
  • Pituitary Gland, Posterior/cytology
  • Pituitary Gland, Posterior/metabolism*
  • Pituitary Gland, Posterior/physiology
  • Neuroglia/metabolism*
  • Zebrafish
  • Pituitary Gland/metabolism
  • Astrocytes/metabolism
  • Brain/metabolism
  • Endothelial Cells/metabolism
  • Cues
  • Tight Junctions/metabolism
(all 17)
PubMed
30449506 Full text @ Dev. Cell
Abstract
The hypothalamo-neurohypophyseal system (HNS) regulates homeostasis through the passage of neurohormones and blood-borne proteins via permeable blood capillaries that lack the blood-brain barrier (BBB). Why neurohypophyseal capillaries become permeable while the neighboring vasculature of the brain forms BBB remains unclear. We show that pituicytes, the resident astroglial cells of the neurohypophysis, express genes that are associated with BBB breakdown during neuroinflammation. Pituicyte-enriched factors provide a local microenvironment that instructs a permeable neurovascular conduit. Thus, genetic and pharmacological perturbations of Vegfa and Tgfβ3 affected HNS vascular morphogenesis and permeability and impaired the expression of the fenestral marker plvap. The anti-inflammatory agent dexamethasone decreased HNS permeability and downregulated the pituicyte-specific cyp26b gene, encoding a retinoic acid catabolic enzyme. Inhibition of Cyp26b activity led to upregulation of tight junction protein Claudin-5 and decreased permeability. We conclude that pituicyte-derived factors regulate the "decision" of endothelial cells to adopt a permeable endothelial fate instead of forming a BBB.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
bns80TgTransgenic Insertion
    jh17TgTransgenic Insertion
      lri500TgTransgenic Insertion
        s843TgTransgenic Insertion
          wz01TgTransgenic Insertion
            wz05TgTransgenic Insertion
              wz06TgTransgenic Insertion
                y7TgTransgenic Insertion
                  y171TgTransgenic Insertion
                    zf44TgTransgenic Insertion
                      1 - 10 of 11
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      Name Type Antigen Genes Isotypes Host Organism
                      Ab1-cldn5monoclonalIgG1Mouse
                      Ab2-mmp9polyclonal
                        IgGRabbit
                        Ab2-mmp14polyclonalIgGRabbit
                        1 - 3 of 3
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                        Orthology
                        No data available
                        Engineered Foreign Genes
                        Marker Marker Type Name
                        CeruleanEFGCerulean
                        EGFPEFGEGFP
                        GAL4EFGGAL4
                        GFPEFGGFP
                        mCherryEFGmCherry
                        NTREFGNTR
                        1 - 6 of 6
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                        Mapping
                        No data available