'Sealing off the CNS': cellular and molecular regulation of blood-brain barriergenesis

•We review the multi-faceted process of blood-brain barriergenesis.•We outline the different properties of the BBB and temporal order of appearance.•Focus on cellular contribution to barriergenesis events, namely pericytes and astrocytes.•Review neural-derived signals, like Wnt ligands, that promote barrier properties.

From their initial ingression into the neural tube to the established, adult vascular plexus, blood vessels within the CNS are truly unique. Covered by a virtually continuous layer of perivascular cells and astrocytic endfeet and connected by specialized cell-cell junctional contacts, mature CNS blood vessels simultaneously provide nutritive blood flow and protect the neural milieu from potentially disruptive or harmful molecules and cells flowing through the vessel lumen. In this review we will discuss how the CNS vasculature acquires blood-brain barrier (BBB) properties with a specific focus on recent work identifying the cell types and molecular pathways that orchestrate barriergenesis.