Distinct cortical migrations from the medial and lateral ganglionic eminences

Recent evidence suggests that projection neurons and interneurons of the ce rebral cortex are generally derived from distinct proliferative zones. Cort ical projection neurons originate from the cortical ventricular zone (VZ), and then migrate radially into the cortical mantle, whereas most cortical i nterneurons 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 stud ies labeled cells by methods that do not distinguish between the proliferat ing cells and those that may have originated elsewhere, we have studied the contribution of the MGE and LGE to cortical interneurons using fate mappin g and genetic methods. Transplantation of BrdU-labeled MGE or LGE neuroepit helium into the basal telencephalon of unlabeled telencephalic slices enabl ed us to follow the fate of neurons derived from each of these primordia, W e have determined that early in neurogenesis GABA-expressing cells from the MGE tangentially migrate into the cerebral cortex, primarily via the inter mediate 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 i n gestation. In addition, by comparing the phenotypes of mouse mutants with differential effects on MGE and LGE migration, we provide evidence that th e MGE and LGE may give rise to different subtypes of cortical interneurons.