Embryonic cortical neural stem cells migrate ventrally and persist as postnatal striatal stem cells

Abstract

Embryonic cortical neural stem cells apparently have a transient existence, as they do not persist in the adult cortex. We sought to determine the fate of embryonic cortical stem cells by following Emx1IREScre; LacZ/EGFP double-transgenic murine cells from midgestation into adulthood. Lineage tracing in combination with direct cell labeling and time-lapse video microscopy demonstrated that Emx1-lineage embryonic cortical stem cells migrate ventrally into the striatal germinal zone (GZ) perinatally and intermingle with striatal stem cells. Upon integration into the striatal GZ, cortical stem cells down-regulate Emx1 and up-regulate Dlx2, which is a homeobox gene characteristic of the developing striatum and striatal neural stem cells. This demonstrates the existence of a novel dorsal-to-ventral migration of neural stem cells in the perinatal forebrain.

Dorsal Radial Glia Generate Olfactory Bulb Interneurons in the Postnatal Murine Brain

“…In vivo fate mapping of the dorsal Emx1 lineage found some olfactory bulb cells, although these were not further described in terms of GABAergic expression (Gorski et al, 2002;Willaime-Morawek et al, 2006). In addition, Willaime-Morawek et al (2006) found that Emx1-derived stem cells migrate from dorsal to ventral regions and generate striatal interneurons, further bolstering the idea of an expanded capability of dorsal cells.…”

“…Whether diffusible factors important for the postnatal neurogenic niche, such as sonic hedgehog, are present in different levels along the dorsoventral axis is unclear. Willaime-Morawek et al (2006) document dorsal Emx1 derived cells migrating to more ventral regions of the SVZ, presumably where they are exposed to the ventral environment and gain competence to generate striatal interneurons. In contrast to their findings, we report that the astrocytic progeny of dorsal radial glia that come to reside at the SVZ border remain in register with their radial glial precursors, apparently not mixing with ventral cells or migrating extensively in a dorsoventral direction.…”

“…We next considered whether the progeny of the dorsal radial glial cells we infected with an adenovirus subsequently migrated to more ventral positions in the SVZ, as was reported for cells of the Emx1 lineage (Willaime-Morawek et al, 2006). We examined the distribution of cells within the SVZ at 3 weeks after infection.…”

“…However, the ability of cells of dorsal origin to upregulate ventral markers in vivo (Letinic et al, 2002;Willaime-Morawek et al, 2006) and in vitro (Hack et al, 2004) points toward difficulties in relying solely on genetic means for fate mapping. We thus used an anatomical fate-mapping strategy to label early postnatal dorsal radial glia and found that these cells retract to form astrocytes in the early postnatal and adult SVZ and generate periglomerular and granule cell interneurons in the olfactory bulb.…”

The Ontogeny of Somatic Stem Cells

“…There are certain somatic stem cell populations that might reasonably be considered stationary (e.g. gut epithelial stem cells) and are dependent on highly localized signaling from the niche (e.g., review S. Takashima and V. Hartenstein) [14], whereas others may have limited migratory behavior, such as cortical neural stem cells migrating ventrally to the subventricular zone along the lateral wall of the striatum [15]. Still, other examples of more dramatic migratory capacity come from studies of the hematopoietic stem cells that move throughout the circulatory system and lodge themselves into different tissues (e.g., review by W. Lensch) [16].…”