News from the brain: the GPR124 orphan receptor directs brain-specific angiogenesis

During development, microvessels acquire specialized functions to meet the requirements of different tissues and organs. The vasculature of the brain constitutes one of the best examples of an organ-specific and highly specialized microvasculature, in which the endothelial cells that line blood vessels form an active permeability barrier and transport system called the blood-brain barrier (BBB); little is known, however, about the molecular mechanisms that instruct endothelial cells toward a BBB phenotype. Now Kuhnert et al. reveal that the orphan heterotrimeric GTP-binding protein-coupled receptor GPR124/TEM5 acts as an organ-specific regulator of brain angiogenesis, required for normal endothelial cell sprouting, migration, and expression of the BBB marker Glut-1 in the forebrain and neural tube. These findings add to our knowledge of brain vascularization and may open up possibilities for new therapeutic regimes to treat several diseases, including stroke, brain tumors, and vascular malformations.