Calcium signaling in chemorepellant Slit2-dependent regulation of neuronal migration

Migration of neuronal precursor cells in the developing brain is guided by extracellular cues, but intracellular signaling processes underlying the guidance of neuronal migration are largely unknown. By examining the migration of cerebellar granule neurons along the surface of cocultured astroglial cells, we found that an extracellular gradient of Slit2, a chemorepellant for neuronal migration in vivo, caused a reversal in the direction of migration without affecting the migration speed. A Slit2 gradient elevated the intracellular concentration of Ca²⁺, probably due to calcium release from the internal store, led to a reversal of the preexisting asymmetric intracellular Ca²⁺ distribution in the soma of migrating neurons, and this reversal was closely related with its action of reversing the migrating direction. Asymmetric Ca²⁺ distribution in the soma was both necessary and sufficient for directing neuronal migration. These results have demonstrated an important role for Ca²⁺ in mediating neuronal responses to Slit2 and suggest a general mechanism for neuronal guidance.