| First Author | Kuhnert F | Year | 2010 |
| Journal | Science | Volume | 330 |
| Issue | 6006 | Pages | 985-9 |
| PubMed ID | 21071672 | Mgi Jnum | J:166127 |
| Mgi Id | MGI:4839817 | Doi | 10.1126/science.1196554 |
| Citation | Kuhnert F, et al. (2010) Essential regulation of CNS angiogenesis by the orphan G protein-coupled receptor GPR124. Science 330(6006):985-9 |
| abstractText | The orphan G protein-coupled receptor (GPCR) GPR124/tumor endothelial marker 5 is highly expressed in central nervous system (CNS) endothelium. Here, we show that complete null or endothelial-specific GPR124 deletion resulted in embryonic lethality from CNS-specific angiogenesis arrest in forebrain and neural tube. Conversely, GPR124 overexpression throughout all adult vascular beds produced CNS-specific hyperproliferative vascular malformations. In vivo, GPR124 functioned cell-autonomously in endothelium to regulate sprouting, migration, and developmental expression of the blood-brain barrier marker Glut1, whereas in vitro, GPR124 mediated Cdc42-dependent directional migration to forebrain-derived, vascular endothelial growth factor-independent cues. Our results demonstrate CNS-specific angiogenesis regulation by an endothelial receptor and illuminate functions of the poorly understood adhesion GPCR subfamily. Further, the functional tropism of GPR124 marks this receptor as a therapeutic target for CNS-related vascular pathologies. |
