Cell adhesion and signaling networks in brain neurovascular units

PURPOSE OF REVIEWCentral nervous system (CNS) neurovascular units are multicellular complexes consisting of neurons and astrocytes, vascular endothelial cells and pericytes, as well as an assortment of growth factors and extracellular matrix (ECM) proteins. Here, I will discuss the current knowledge of signaling networks essential for the development and physiology of CNS neurovascular units, particularly in the brain. RECENT FINDINGSMolecular genetic studies have identified various signaling proteins that regulate the formation and function of CNS neurovascular units. These include members of the integrin family of ECM adhesion receptors, ECM proteins such as Wnts and latent transforming growth factor βs, and various transcriptional regulators, including β-catenin and the inhibitors of DNA binding (Ids). SUMMARYNeurovascular units are the cellular and molecular interfaces between the circulatory system and the CNS. Recent molecular genetic analyses in mice and other model organisms have revealed the first mechanisms underlying bidirectional communication between neural and vascular components. In particular, ECM-mediated adhesion and signaling pathways have been identified as essential for neurovascular development and physiology. Understanding how these various gene products normally control neurovascular unit formation and function will lend new insights into the causes and possible treatments of debilitating neurovascular-related diseases such as birth defects, stroke, and age-related dementia.