Functional role of a glycolipid in directional movements of neurons

Abstract

Migration of neurons from their site of origin to their final destination is a critical and universal step in the formation of the complex structure of the nervous system. The migratory process is thought to be governed in part by genetically and epigenetically defined sequences of signals which are interpreted by migrating cells. The molecular mechanisms that underlie neuronal migration have been the subject of intense investigation. As in other developmental processes, many molecules must participate in neuronal migration. Some molecules, such as cell adhesion molecules and motor proteins, may contribute to discrete steps in the migration act; others, like extracellular signaling molecules, may regulate the activation and/or termination of the migration program. In this article we review findings from our group that demonstrate the functional role(s) of a specific glycolipid in neuronal migration and neurite outgrowth in the developing and adult nervous system.

Immunoblockage of 9-O-Acetyl GD3 Ganglioside Arrests theIn VivoMigration of Cerebellar Granule Neurons

“…In addition, it has been shown that ␣3␤1 integrin plays a key role in the control of glial-guided neuronal migration during the formation of the cerebral cortex layers (Dulabon et al, 2000), and ␤1 integrin expression has been described in the cerebellum during development (Husmann and Sievers, 1985). These results combined with results described in this paper and previous reports from our group (for review, see Mendez-Otero and Santiago, 2001) support the assumption that 9-O-acetyl GD3 may interact with integrin receptors and therefore be involved in the control and/or modulation of the neuron-glia interactions and, consenquently, in the neuronal migration program during cerebellar development. Because gangliosides have been associated with glycosynapses in non-neuronal cells, it would be interesting to verify whether such structures are also present in the developing cerebellum and their role in the gliophilic migration of granule cells.…”

“…In these regions, cells are found with migratory profiles. The observation that labeling with Jones mAb is restricted to regions of cell migration is consistent with previous reports that have suggested that the ganglioside 9-O-acetyl GD3 is a marker for neuronal migration in the developing Schlosshauer et al, 1988;Mendez-Otero and Ramon-Cueto, 1994;Miyakoshi et al, 2001;Santiago et al, 2001) (for review, see Mendez-Otero and Santiago, 2001) and adult (Mendez-Otero and Cavalcante, 1996) nervous system. We also show that the antibody against 9-Oacetyl GD3 arrests granule cells in the external granular cell layer and diminishes the number of BrdU-positive granule cells in the internal granular cell layer by 57%.…”

Cell migration in the postnatal subventricular zone

“…Infusion of clustered soluble EphB2 and ephrin-B2 disrupted chain migration in the SVZ/RMS. However, this result may be due to a direct effect on proliferation (22) It may not be surprising that ganglioside 9-O-acGD3 is involved in RMS cell migration since it is expressed in a spatiotemporally regulated manner in regions in which cell migration and process outgrowth occur in the developing CNS and peripheral nervous system (48). This glycolipid has been directly implicated in external granule cell radial migration in the cerebellum (48,49).…”

“…However, this result may be due to a direct effect on proliferation (22) It may not be surprising that ganglioside 9-O-acGD3 is involved in RMS cell migration since it is expressed in a spatiotemporally regulated manner in regions in which cell migration and process outgrowth occur in the developing CNS and peripheral nervous system (48). This glycolipid has been directly implicated in external granule cell radial migration in the cerebellum (48,49). Initially it was thought to mediate only gliophilic migration via a homophilic interaction of this ganglioside on the surface of migrating neuronal precursors and radial glial cells (48).…”

“…This glycolipid has been directly implicated in external granule cell radial migration in the cerebellum (48,49). Initially it was thought to mediate only gliophilic migration via a homophilic interaction of this ganglioside on the surface of migrating neuronal precursors and radial glial cells (48). However, 9-O-acGD3 molecules were also shown to be expressed in the developing and adult SVZ/RMS labeling migratory profiles (41).…”