Neurogenesis of GABAergic neurons in the neocortex

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In the developing rodent neocortex, the glutamatergic neurons are supplied by proliferation of radial glias in the ventricular zone(VZ) of the pallium, while the GABAergic neurons are produced in the the ganglionic eminence(GE), a subpallial structure, and then come into the neocortex by tangential cell migration. However, cell lineage analyses with a retrovirus have often revealed clonally related GABAergic neuron pairs located closely within the neocortex. Following these reports, we speculated that some of the GABAergic neurons were produced in the rodent neocortex. In GAD67-GFP knock-in mice, we found colocalization of single-pulse (30 min) BrdU and GFP, or Ki-67 and GFP in the subventricular zone(SVZ)and the intermediate zone(IZ) of the neocortex at birth. One forth of GFP-positive cells in the SVZ and the IZ were positive for Ki-67. And one thirds of GFP-positive cells in the neocortex were positive for nestin. These data indicate that a portion of GAD67-positivecells are proliferative, suggesting these cells are the progenitorscommitted to GABAergic neurons. To assess whether the putative progenitors for GABAergic neurons were also supplied by tangential cellmigration from the GE, we injected an adenovirus or retrovirus witha construct (CA promoter-loxP-GFP-loxP) into the ventricle of Emx1-Cre knock-in mouse embryos : These viruses reveal the origin of the Emx1-negative cells in the neocortex. We found some of the putative GABAergic neuron progenitors in the neocortex were in Emx1-negativelineage and derived from the subpallial VZ. We conclude that the GABAergic neurons in the rodent neocortex are supplied not only by migration of postmitotic GABAergic neurons from the GE, but also by proliferation of their progenitors immigrated from the GE to the neocortex.