Extracellular matrix functions during neuronal migration and lamination in the mammalian central nervous system

Abstract

Extracellular matrix (ECM) glycoproteins are expressed in the central nervous system (CNS) in complex and developmentally regulated patterns. The ECM provides a number of critical functions in the CNS, contributing both to the overall structural organization of the CNS and to control of individual cells. At the cellular level, the ECM effects its functions by a wide range of mechanisms, including providing structural support to cells, regulating the activity of second messenger systems, and controlling the distribution and local concentration of growth and differentiation factors. Perhaps the most well known role of the ECM is as a substrate on which motile cells can migrate. Genetic, cell biological and biochemical studies provide strong evidence that ECM glycoproteins such as laminins, tenascins and proteoglycans control neuronal migration and positioning in several regions of the developing and adult brain. Recent findings have also shed important new insights into the cellular and molecular mechanisms by which reelin regulates migration. Here we will summarize these findings, emphasizing the emerging concept that ECM glycoproteins promote different modes of neuronal migration such as radial, tangential and chain migration. We also discuss several studies demonstrating that mutations in ECM glycoproteins can alter neuronal positioning by cell non-autonomous mechanisms that secondarily affect migrating neurons.

Cas Adaptor Proteins Organize the Retinal Ganglion Cell Layer Downstream of Integrin Signaling

“…The stratification of cell bodies within developing laminar structures is a progressive event that occurs throughout the nervous system and is critical for the assembly of neural circuits (Franco and Müller, 2011). The process by which the single-cell retina GCL is generated provides a relatively simple example of how laminar organization within the nervous system arises.…”

Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia

“…Importantly, other PNN elements, namely Reelin and semaphorin 3A, have been shown to be involved in the pathophysiology of SZ, although not directly as PNN components (Abdolmaleky et al, 2005a; Carulli et al, 2013a; Costa et al, 2001; Dick et al, 2013; Eastwood et al, 2003; Fatemi, 2005; Impagnatiello et al, 1998; Vo et al, 2013b). In particular, Reelin has been extensively investigated for its role in brain development, synaptic regulation during adulthood and involvement in several brain disorders, including SZ and bipolar disorder; although some of these aspects will be mentioned in this review, we refer to comprehensive publications by other groups for details (Abdolmaleky et al, 2005a; Akbarian and Huang, 2006; Barros et al, 2011; Campo et al, 2009; Chen et al, 2005; Costa et al, 2001; Curran and D’Arcangelo, 1998; Dityatev et al, 2006; Eastwood and Harrison, 2006; Fatemi, 2001; Flashner et al, 2013; Folsom and Fatemi, 2013; Franco and Muller, 2011; Frotscher, 2010; Frotscher et al, 2009a, b; Guidotti et al, 2011; Guidotti et al, 2000; Honda et al, 2011; Impagnatiello et al, 1998; Lakatosova and Ostatnikova, 2012; Pesold et al, 1999; Sinagra et al, 2005; Stranahan et al, 2013). …”

Inhibitors of myelination: ECM changes, CSPGs and PTPs

“…Fibronectin is expressed in neuroepithelial cells of the ventricular zone and radial glial cells during development, as well as the vasculature (Jones et al, 1982; Pearlman and Sheppard, 1996). During development, the ECM regulates neuronal and glial migration and process outgrowth, with early matrix being loose and allowing extensive cell migration (Carbonetto, 1984; Franco and Müller, 2011; Rutka et al, 1988; Liu et al, 2006; Pearlman and Sheppard, 1996; Sanes, 1989; Schwartz and Domowicz, 2004; and many others). With CNS maturation, the ECM composition changes to form a firmer matrix (Zimmermann and Dours-Zimmermann, 2008).…”