Development of blood-brain barrier endothelial cells

The vascular system of the central nervous system is derived from capillary endothelial cells, which have invaded the early embryonic neuroectoderm. This process is called angiogenesis and is probably regulated by brain-derived factors. Vascular endothelial cell growth factor (VEGF) is an angiogenic growth factor whose expression correlated with embryonic brain angiogenesis, i.e. expression is high in the embryonic brain when angiogenesis occurs and low in the adult brain when angiogenesis is shut off under normal physiological conditions. VEGF receptors 1 and 2 (flt-1 and flk-l) as well as another pair of receptors (tie-1 and tie-2) are receptor tyrosine kinases specifically expressed in endothelial cells. Expression of these receptors is high during brain angiogenesis but low in adult blood-brain barrier endothelium. Signal transduction by these or other receptors involved in endothelial cell growth and differentiatian may be mediated by lyn, a nonreceptor tyrosine kinase expressed in brain endothelium. Induction and maintenance of blood-brain barrier endothelial cell characteristics (complex tight junctions, low number of vesicles, specialized transport systems) are regulated by the local brain environment; e.g. astrocytes. Tight junctions between brain endothelial cells are the structural basis for the paracellular impermeability and high electrical resistance of blood-brain barrier endothelium. Association of tight junction particles with the P-face along with the intercellular adhesion forces rather than the number or branching frequency of tight junction strands correlated with BBB development and function suggesting that the cytoplasmic anchoring of the tight junctions plays an important role.