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

被引：13

作者：

Chen, Zhihua ^{[1
]}

Morales, John E. ^{[1
]}

Avci, Naze ^{[1
]}

Guerrero, Paola A. ^{[1
]}

Rao, Ganesh ^{[1
]}

Seo, Je Hoon ^{[2
]}

McCarty, Joseph H. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA

[2] Chungbuk Natl Univ, Dept Anat, Coll Med, Chungbuk 28644, South Korea

来源：

DEVELOPMENT | 2020年 / 147卷 / 18期

基金：

美国国家卫生研究院;

关键词：

Vascular basement membrane; Microenvironment; Neurovascular unit; Extracellular matrix; Astrocyte; Barriergenesis; RECEPTOR ENDOCYTOSIS; CEREBRAL-HEMORRHAGE; NERVOUS-SYSTEM; GENE; DEGENERATION; MECHANISMS; NOTCH;

D O I：

10.1242/dev.193094

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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