BLOCKAGE OF 9-O-ACETYL GANGLIOSIDES INDUCES MICROTUBULE DEPOLYMERIZATION IN GROWTH CONES AND NEURITES

Gangliosides have been implicated in numerous cellular functions in th e developing nervous system. The expression of 9-O-acetyl gangliosides recognized by the JONES mAb correlates with periods of cell migration and axonal pathfinding. In vitro, addition of JONES induces growth co ne collapse of dorsal root ganglion neurons. This suggests a modulator y activity of 9-O-acetyl gangliosides on growth cone motility and/or a dhesion. In this study we have investigated the effect of JONES mAb ad dition on the cytoskeleton of dorsal root ganglion neurons in vitro. W e have shown that blockage of 9-O-acetyl gangliosides induces the appe arance of lateral spikes along the neurites in addition to the effect on the growth cone. Microfilament and microtubular rearrangements acco mpany these structural modifications. We present evidence that the mai n effect of JONES mAb is to induce microtubule depolymerization both i n growth cones and neurites. Together with the analysis on the spatial distribution of these gangliosides along the cell surface, our result s suggest that 9-O-acetyl gangliosides recognized by JONES mAb might s erve a concerted action, modulating growth cone motility and axonal br anch formation.