Fate mapping by piggyBac transposase reveals that neocortical GLAST+ progenitors generate more astrocytes than Nestin+ progenitors in rat neocortex

• Published in: Cerebral cortex (New York, N.Y. 1991) Vol. 24; no. 2; pp. 508 - 520
• Main Authors: Siddiqi, Faez, Chen, Fuyi, Aron, Abraham W, Fiondella, Christopher G, Patel, Komal, LoTurco, Joseph J
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.02.2014
• Subjects: Animals; Astrocytes - physiology; Cell Lineage - physiology; Cells, Cultured; Electroporation; Excitatory Amino Acid Transporter 1 - metabolism; HEK293 Cells; Humans; Integrases - genetics; Integrases - metabolism; Neocortex - embryology; Neocortex - physiology; Nestin - metabolism; Neural Stem Cells - physiology; Neurogenesis - physiology; Neurons - physiology; Pyramidal Cells - physiology; Rats; Rats, Wistar; Transposases - genetics; Transposases - metabolism; piggyBac transposon system; neocortex; Cre/loxP; lineage tracing; fate specification
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhs332

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.