In this study, we used in utero electroporation (IUE) to fate-map GLAST+ and Nestin+ neocortical progenitor populations at the VZ surface. Similarly, it remains unclear when progenitors at the surface of the neocortical VZ transition from neuronal to astrocyte-generating progenitors, and whether subpopulations cohabit the same regions of the neocortical VZ. It is not currently known whether the Nestin+ and GLAST+ radial progenitor populations originating from the embryonic ventricular zone (VZ) in the neocortex differ in terms of the types of the astrocyte-generating mechanisms they display. 1993), and recently, it has been shown by 2-photon live-cell imaging that local proliferation of astrocytes within neocortical lamina contributes significantly to the generation of astrocytes ( Ge et al. The proliferation of astrocyte progenitors occurs both within the SVZ in prenatal and postnatal cortex ( Levison et al. 1983) and by the proliferation of astrocyte-generating progenitors and astrocytes away from the VZ surface ( Levison et al. The generation of the astrocyte in the neocortex occurs both by a direct transitioning of radial glia to astrocytes ( Levitt et al. Similarly, in vivo fate-mapping methods with Cre-recombinase (CRE) transgenes show that Nestin+ and glutamate and aspartate transpoter (GLAST+) radial glia populations in the forebrain generate significantly more neurons or more astrocytes, respectively, in mice ( Anthony et al. 2002 Kriegstein and Götz 2003 Costa et al. Birthdating and lineage analysis indicate that progenitors in the neocortex undergo a marked change over time in potential to generate neurons and then astrocytes ( Götz et al. Analysis of progenitors in the neocortical VZ by immunocytochemistry, retroviral lineage tracing, and live-cell imaging in rodents indicates that most, if not all, dividing cells in the VZ arise from, or are themselves, radial glial cells ( Noctor et al. Radial glia provide structural scaffolds for the migration of immature neurons ( Rakic 1972 Sidman and Rakic 1973) and are the major progenitor cell type producing neurons and astrocytes in the developing neocortex ( Noctor et al. This study provides in vivo evidence that by mid-corticogenesis (E15), VZ progenitor populations have significantly diversified in terms of their potential to generate astrocytes and neurons.Ĭre/loxP, fate specification, lineage tracing, neocortex, piggyBac transposon system Introduction Finally, we used a multicolor clonal labeling method to show that the GLAST+ population labeled at E15 generates astrocyte progenitors that produce larger, spatially restricted, clonal clusters than the Nestin+ population. By E18, birth-dated progeny of GLAST+ progenitors give rise to 2–3-fold more neocortical astrocytes than do Nestin+ progenitors. To determine when birth-dated progeny within GLAST+ and Nestin+ populations diverge, we used a Cre/loxP fate-mapping system in which plasmids are lost after a cell division. By E15, the GLAST+ progenitor population diverges significantly to produce lineages with 5–10-fold more astrocytes relative to neurons than generated by the Nestin+ population. GLAST+ and Nestin+ progenitors at embryonic day 13 (E13) produce lineages containing similar rations of neurons and astrocytes. We applied novel piggyBac transposase lineage tracking methods to fate-map progenitor populations positive for Nestin or glutamate and aspartate transpoter (GLAST) promoter activities in the rat neocortex. Progenitors within the neocortical ventricular zone (VZ) first generate pyramidal neurons and then astrocytes.
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