Polarized increase of calcium and nucleokinesis in tangentially migrating neurons

Cortical interneurons originate from the ganglionic eminences and reach their final position in the cortex via tangential migratory routes. The mechanisms of this migration are poorly understood. Here we have performed confocal time-lapse analysis of cell movement in the intermediate zone of embryonic mouse cortical slices in order to directly visualize their mode of migration. Tangentially migrating neurons moved by nucleokinesis, characterized by active phases of discontinuous advances of the nucleus followed by periods of quiescence. Dissociated cells from the ganglionic eminences also showed nucleokinesis associated with an increase of intracellular calcium, [Ca(2+)](i) Calcium elevation was greatest in the proximal region of the leading process, a zone with a wide distribution of gamma-tubulin. General increases in [Ca(2+)](i) elicited by microperfussion with neurotransmitters did not elicit nucleokinesis. These results show that tangential migration uses nucleokinesis, a cell-intrinsic process in which calcium signalling is local, directional and highly regulated.