The molecular basis of the blood brain barrier differentiation and maintenance. Is it still a mystery?

Endothelial cells (ECs) differ in morphology and functional responses in the different regions of the vascular tree. During embryo development they acquire organ specific characteristics to respond to the needs of the perfused organs. The brain microvasculature is a striking example of this process. This particular vasculature develops unique properties to assure a tight control of permeability between blood and the underlying nervous system. To this end, these cells present well developed cell to cell junctions, tight basement membrane and express a series of transporters which support the passage of nutrients and toxic agents inside or outside the brain, respectively. This highly differentiated EC phenotype is induced and maintained by the cross-talk with the surrounding cells such as pericytes and astrocytes. Recent evidence highlights the molecular basis of this cross-talk (constituting the neurovascular unit) and opens new perspectives in the development of drugs which modulate blood-brain-barrier (BBB) permeability properties. In this review we describe the specific features of the BBB and we discuss recent data on the role of Wnt as a mediator of brain angiogenesis and BBB differentiation.