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  • The vascular endothelial cell-expressed prion protein doppel promotes angiogenesis and blood-brain barrier development.

The vascular endothelial cell-expressed prion protein doppel promotes angiogenesis and blood-brain barrier development.

Development (Cambridge, England) (2020-09-09)
Zhihua Chen, John E Morales, Naze Avci, Paola A Guerrero, Ganesh Rao, Je Hoon Seo, Joseph H McCarty, Zhihua Chen, John E Morales, Naze Avci, Paola A Guerrero, Ganesh Rao, Je Hoon Seo, Joseph H McCarty
ABSTRACT

The central nervous system (CNS) contains a complex network of blood vessels that promote normal tissue development and physiology. Abnormal control of blood vessel morphogenesis and maturation is linked to the pathogenesis of various neurodevelopmental diseases. The CNS-specific genes that regulate blood vessel morphogenesis in development and disease remain largely unknown. Here, we have characterized functions for the gene encoding prion protein 2 (Prnd) in CNS blood vessel development and physiology. Prnd encodes the glycosylphosphatidylinositol (GPI)-linked protein doppel, which is expressed on the surface of angiogenic vascular endothelial cells, but is absent in quiescent endothelial cells of the adult CNS. During CNS vascular development, doppel interacts with receptor tyrosine kinases and activates cytoplasmic signaling pathways involved in endothelial cell survival, metabolism and migration. Analysis of mice genetically null for Prnd revealed impaired CNS blood vessel morphogenesis and associated endothelial cell sprouting defects. Prnd-/- mice also displayed defects in endothelial barrier integrity. Collectively, these data reveal novel mechanisms underlying doppel control of angiogenesis in the developing CNS, and may provide new insights about dysfunctional pathways that cause vascular-related CNS disorders.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Glial Fibrillary Acidic Protein Antibody, clone GA5, clone GA5, Chemicon®, from mouse
Sigma-Aldrich
Blasticidine S hydrochloride
Sigma-Aldrich
Anti-Laminin antibody produced in rabbit, 0.5 mg/mL, affinity isolated antibody, buffered aqueous solution