Multidirectional and multizonal tangential migration of GABAergic interneurons in the developing cerebral cortex

Most GABAergic interneurons originate from the basal forebrain and migrate tangentially into the cortex. The migratory pathways and mode of interneuron migration within the developing cerebral cortex, however, previously was largely unknown. Time-lapse imaging and in vivo labelling with glutamate decarboxylase ( GAD) 67-green fluorescence protein ( GFP) knock-in embryonic mice with expression of GFP in gamma-aminobutyric acid ( GABA) ergic neurons indicated that multidirectional tangential ( MDT) migration of interneurons takes place in both the marginal zone ( MZ) and the ventricular zone ( VZ) of the cortex. Quantitative analysis of migrating interneurons showed that rostrocaudally migrating neurons outnumber those migrating mediolaterally in both of these zones. In vivo labelling with a lipophilic dye showed that the MDT migration in the MZ occurs throughout the cortex over distances of up to 3 mm during a period of a few days. These results indicate that MZ cortical interneurons undergo a second phase of tangential migration in all directions and over long distances, after reaching the cortex by dorsomedial tangential migration. The MDT migration in the MZ may disperse and intermix interneurons within the cortex, resulting in a balanced distribution of interneuron subtypes.