Development of the blood–brain barrier

The blood-brain barrier (BBB) is a term used to describe the specialized properties of vasculature in the central nervous system (CNS) that regulate the exchange of ions, molecules and cells, thereby maintaining CNS homeostasis. These BBB properties are largely possessed by vascular endothelial cells, which exhibit molecular specializations that distinguish them from endothelial cells in other organs. BBB development - orchestrated by complex interactions between endothelial cells, neural progenitor cells, pericytes, astrocytes, neurons and other cell types that form the neurovascular unit - is initiated concurrently with CNS angiogenesis and continues during expansion and maturation of the vasculature. Importantly, the Wnt/β-catenin signaling pathway plays a central role in barriergenesis, the initial acquisition of BBB phenotype in endothelial cells. In this Review, we summarize current understanding of BBB development, including timing and underlying cellular and molecular mechanisms. We also discuss established and emerging techniques for studying BBB development and highlight important unanswered questions in the field.