MoD Special Issue on interactions at the neurovascular interface

Both the vasculature and the nervous system form extensively branched networks in the vertebrate body, interact with very different tissue environments and establish connections over long distances. Although there are many obviousmorphological, functional andmolecular differences between blood vessels and nerve fibers, striking conceptual similarities in the assembly of these networks through guided growth and branching processes are undeniable. This resemblance is not just superficial, but based on overlapping sets of mechanistic principles and molecular regulators. Growing nerve fibers extend with the help of distal, filopodia-extending structures termed growth cones. In an analogous manner, blood vessel sprouting involves the coordinated action of multiple endothelial cells, one of which extends long filopodia, leads the extending sprout as its tip in a growth cone-like fashion and, finally, establishes new connections with other sprouts or vessels. Growing nerve fibers and vessels also respond to overlapping sets of guidance systems and molecular cues. Certain vessels and nerves form in a highly aligned fashion, which can bemediated by nerve-derived signals that act on endothelial cells or, conversely, the formation of nerve fibers along a preformed vessel template. Vascular and neural cells work together to form a number of functional tissue compartments. Endothelial cells, supporting cells of the vessel wall (i.e., pericytes) and astrocytes assemble the neurovascular unit, which establishes the blood–brain-barrier and thereby separates the circulation from the central nervous system. This separation prevents the entry of potentially harmful molecules and immune cells into the brain tissue. Similar blood–retina and blood–nerve barriers protect the eye and nerve fibers.