Interactions of developing neurons with the extracellular matrix

Abstract

The differentiation and morphogenesis of neural tissues involves a diversity of interactions between neural cells and their environment. Many potentially important interactions occur with the extracellular matrix (ECM), a complex association of extracellular glycoproteins organized into aggregates and polymers. In this article, we discuss recent findings on neuronal interactions with the ECM and their roles in neural cell migration and neurite growth. First, we examine the expression and putative functions of the molecules of the neural ECM. Second, we discuss cell surface molecules that mediate neural interactions with ECM components. Last, we address proteoglycans (PGs), a diverse class of glycoproteins, present both as ECM components and as cell surface molecules, which may mediate neural interactions with their environment. The best-understood cellular interactions with the ECM are adhesive, mediated by binding between specific cell surface molecules and cell binding domains of ECM components (Strittmater and Fishman, 199 1; Damsky and Werb, 1992). Cellsubstratum adhesion is necessary for major cell movements of neuron morphogenesis, that is, the migrations of neural cells and their precursors and the migratory behavior ofgrowth cones at the extending tips of axons and dendrites. As cells move, adhesive molecules at the surface of the leading edge of a migrating cell or growth cone bind to ligands on other cell surfaces or ECM components. These bonds stabilize filopodia and lamellipodia, and, in some cases, provide anchorage against which cytoskeletal filaments, associated with the plasma membrane, exert forces to pull the cell or growth cone forward. Thus, ECM has been primarily viewed as an adhesive substratum to provide traction for migrating cells and to stabilize the position and, perhaps, the state of differentiation of nonmotile cells. However, the interactions between neural cells and the ECM are not longer regarded as only adhesive or mechanical. Two points are now clear. First, some of these interactions are definitely not adhesive, but, rather, they may even be antiadhesive (Chiquet-Ehrismann, 199 1). Second, evidence has accumulated to indicate that the cell surface molecules that mediate cell-cell and cell-ECM interactions (immunoglobulin superfamily, cad-Preparation of this review was supported by NIH Grants HDI 9950 and NS28807

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