Accumulating evidence points to a primary role for non-myelinating glia as principal mediators of homeostasis in the central nervous system (CNS). However, the origins of the basis for glial heterogeneity are not well understood. Our recent studies contribute to an emerging view that the extracellular matrix (ECM) provides clues to glia underling their specialized functions and, more importantly, the nature of how glia change in relation to neuropathology. In this review, we discuss how the dynamic mosaic of CNS ECM impacting CNS health and disease. Specifically, we focus on the roles of select extracellular matrix proteins, namely fibronectin (Fn), vitronectin (Vn), laminin (Ln) and tenascin-c (TnC), as prototypes for how ECM can modulate glial functions. We discuss the differences in expression patterns in the developing and adult CNS and relate these ECM molecules to specific changes in glial functions in neurological diseases. We also discuss how experiments have revealed the role of ECM molecules’ influence on CNS development and the response of glia to injury and inflammation. We provide a new model to explain the nature of glial diversity as an adaptive response to the extracellular milieu, and provide a different approach to understand the complex nature of glia heterogeneity.
Part of the book: Composition and Function of the Extracellular Matrix in the Human Body