In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain

TLDR

Neurons generated in the developing basal forebrain are thought to migrate long distances perpendicular to radial glia, but their in‑vivo origins, pathways, and ultimate destinations remain poorly characterized. We used ultrasound‑guided in‑utero transplantation to trace the migratory routes and fates of lateral and medial ganglionic eminence cells in 13.5‑day‑old mouse embryos. Our results show that LGE cells travel ventrally and anteriorly to populate the striatum, nucleus accumbens, olfactory tubercle, and olfactory bulb, whereas MGE cells migrate dorsally into the neocortex via the subventricular zone, giving rise to transient subpial granule neurons and stable GABAergic interneurons.

Abstract

Recent studies suggest that neurons born in the developing basal forebrain migrate long distances perpendicularly to radial glia and that many of these cells reach the developing neocortex. This form of tangential migration, however, has not been demonstrated in vivo, and the sites of origin, pathways of migration and final destinations of these neurons in the postnatal brain are not fully understood. Using ultrasound-guided transplantation in utero, we have mapped the migratory pathways and fates of cells born in the lateral and medial ganglionic eminences (LGE and MGE) in 13.5-day-old mouse embryos. We demonstrate that LGE and MGE cells migrate along different routes to populate distinct regions in the developing brain. We show that LGE cells migrate ventrally and anteriorly, and give rise to the projecting medium spiny neurons in the striatum, nucleus accumbens and olfactory tubercle, and to granule and periglomerular cells in the olfactory bulb. By contrast, we show that the MGE is a major source of neurons migrating dorsally and invading the developing neocortex. MGE cells migrate into the neocortex via the neocortical subventricular zone and differentiate into the transient subpial granule neurons in the marginal zone and into a stable population of GABA-, parvalbumin- or somatostatin-expressing interneurons throughout the cortical plate.