Blood-brain barrier regulation: Environmental cues controlling the onset of barrier properties

The existence of a barrier between the central nervous system (CNS) and the systemic circulation has been described over one hundred years ago. Since the discovery that this barrier was instigated by the barrier properties of the brain endothelial cells, research has focused on the identification of pathways how the brain endothelial cells are instructed to form the highly specialized blood-brain barrier (BBB). Even though our current understanding of BBB development is far from complete, recent literature shows a rise in knowledge of CNS-specific cues that can drive BBB development.   In this commentary, we will provide a brief overview of brain selective factors that are critical in the development of barrier properties in the brain endothelium; in particular the role of retinoic acid will be discussed.