1. Academic Validation
  2. Pituicyte Cues Regulate the Development of Permeable Neuro-Vascular Interfaces

Pituicyte Cues Regulate the Development of Permeable Neuro-Vascular Interfaces

  • Dev Cell. 2018 Dec 17;47(6):711-726.e5. doi: 10.1016/j.devcel.2018.10.017.
Savani Anbalagan 1 Ludmila Gordon 1 Janna Blechman 1 Ryota L Matsuoka 2 Preethi Rajamannar 1 Einav Wircer 1 Jakob Biran 3 Adriana Reuveny 1 Dena Leshkowitz 4 Didier Y R Stainier 2 Gil Levkowitz 5
Affiliations

Affiliations

  • 1 Department of Molecular Cell Biology, Weizmann Institute of Science, PO Box 26, Rehovot 7610001, Israel.
  • 2 Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
  • 3 Department of Poultry and Aquaculture, Agricultural Research Organization, Rishon Letziyon 7528809, Israel.
  • 4 Bioinformatics Unit, LSCF Weizmann Institute of Science, PO Box 26, Rehovot 7610001, Israel.
  • 5 Department of Molecular Cell Biology, Weizmann Institute of Science, PO Box 26, Rehovot 7610001, Israel. Electronic address: gil.levkowitz@weizmann.ac.il.
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.

Keywords

Claudin; arginine-vasopressin; astroglia; blood-brain barrier; fenestrae; microglia; neuroendocrine; neurovascular unit; oxytocin; pituicyte; plvap; tight junction; vascular permeability; zebrafish.

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