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

Abstract

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 5-10-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 2-3-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.