Distinct cortical migrations from the medial and lateral ganglionic eminences

TLDR

Projection neurons arise from the cortical ventricular zone and migrate radially, whereas most interneurons originate in the basal telencephalon and migrate tangentially, with the medial and lateral ganglionic eminences serving as the two primary sources. The study aims to delineate the distinct contributions of the medial and lateral ganglionic eminences to cortical interneuron populations using fate‑mapping and genetic techniques. BrdU‑labeled MGE or LGE neuroepithelium was transplanted into unlabeled telencephalic slices to trace the fate of neurons derived from each primordium. Early in neurogenesis, GABAergic cells from the MGE migrate tangentially into the cortex via the intermediate zone while LGE‑derived cells do not; later, LGE cells migrate through the subventricular zone, some reaching the cortical plate and expressing GABA while others remain proliferative, indicating that MGE and LGE generate distinct interneuron subtypes.

Abstract

ABSTRACT 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.