Stewart A. Anderson

Although previous analyses indicate that neocortical neurons originate from the cortical proliferative zone, evidence suggests that a subpopulation of neocortical interneurons originates within the subcortical telencephalon. For example, gamma-aminobutyric acid (GABA)-expressing cells migrate in vitro from the subcortical telencephalon into the neocortex. The number of GABA-expressing cells in neocortical slices is reduced by separating the neocortex from the subcortical telencephalon. Finally, mice lacking the homeodomain proteins DLX-1 and DLX-2 show no detectable cell migration from the subcortical telencephalon to the neocortex and also have few GABA-expressing cells in the neocortex.

Recent evidence suggests that projection neurons and interneurons of the cerebral cortex are generally derived from distinct proliferative zones. Cortical projection neurons originate from the cortical ventricular zone (VZ), and then migrate radially into the cortical mantle, whereas most cortical interneurons originate from the basal telencephalon and migrate tangentially into the developing cortex. Previous studies using methods that label both proliferative and postmitotic cells have found that cortical interneurons migrate from two major subdivisions of the developing basal telencephalon: the medial and lateral ganglionic eminences (MGE and LGE). Since these studies labeled cells by methods that do not distinguish between the proliferating cells and those that may have originated elsewhere, we have studied the contribution of the MGE and LGE to cortical interneurons using fate mapping and genetic methods. Transplantation of BrdU-labeled MGE or LGE neuroepithelium into the basal telencephalon of unlabeled telencephalic slices enabled us to follow the fate of neurons derived from each of these primordia. We have determined that early in neurogenesis GABA-expressing cells from the MGE tangentially migrate into the cerebral cortex, primarily via the intermediate zone, whereas cells from the LGE do not. Later in neurogenesis, LGE-derived cells also migrate into the cortex, although this migration occurs primarily through the subventricular zone. Some of these LGE-derived cells invade the cortical plate and express GABA, while others remain within the cortical proliferative zone and appear to become mitotically active late in gestation. In addition, by comparing the phenotypes of mouse mutants with differential effects on MGE and LGE migration, we provide evidence that the MGE and LGE may give rise to different subtypes of cortical interneurons.