Morphogens and blood-brain barrier function in health and disease

The microvasculature of the brain forms a protective blood-brain barrier (BBB) that ensures a homeostatic environment for the central nervous system (CNS), which is essential for optimal brain functioning. The barrier properties of the brain endothelial cells are maintained by cells surrounding the capillaries, such as astrocytes and pericytes. Together with the endothelium and a basement membrane, these supporting cells form the neurovascular unit (NVU). Accumulating evidence indicates that the supporting cells of the NVU release a wide variety of soluble factors that induce and control barrier properties in a concentration-dependent manner. The current review provides a comprehensive overview of how such factors, called morphogens, influence BBB integrity and functioning. Since impaired BBB function is apparent in numerous CNS disorders and is often associated with disease severity, we also discuss the potential therapeutic value of these morphogens, as they may represent promising therapies for a wide variety of CNS disorders.