Fate Mapping by PiggyBac Transposase Reveals That Neocortical GLAST+ Progenitors Generate More Astrocytes Than Nestin+ Progenitors in Rat Neocortex

Progenitors within the neocortical ventricular zone (VZ) first generate pyramidal neurons and then 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. GLAST and Nestin progenitors at embryonic day 13 (E13) produce lineages containing similar rations of neurons and astrocytes. By E15, the GLAST progenitor population diverges significantly to produce lineages with 510-fold more astrocytes relative to neurons than generated by the Nestin population. 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 E18, birth-dated progeny of GLAST progenitors give rise to 23-fold more neocortical astrocytes than do Nestin progenitors. 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. 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.