Sustained Pax6 Expression Generates Primate-like Basal Radial Glia in Developing Mouse Neocortex

• Published in: PLoS biology 2015-08, Vol.13 (8), p.e1002217-e1002217
• Main Authors: Wong, Fong Kuan, Fei, Ji-Feng, Mora-Bermúdez, Felipe, Taverna, Elena, Haffner, Christiane, Fu, Jun, Anastassiadis, Konstantinos, Stewart, A Francis, Huttner, Wieland B
• Format: Article
• Language: English
• Subjects: Animals; Biological Evolution; Biology; Brain; Cell cycle; Cell division; Eye Proteins - metabolism; Female; Fluorescent Antibody Technique; Gene expression; Genetic aspects; Homeodomain Proteins - metabolism; Identification and classification; Male; Mammals; Mice; Mice, Inbred C57BL; Mice, Transgenic; Monkeys & apes; Neocortex; Neocortex - cytology; Neocortex - embryology; Neocortex - metabolism; Neural Stem Cells - metabolism; Neuroglia; Neuroglia - metabolism; Neurons; Neurons - metabolism; Paired Box Transcription Factors - metabolism; PAX6 Transcription Factor; Primates; Repressor Proteins - metabolism; Rodents; Transcription factors
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1002217

The evolutionary expansion of the neocortex in mammals has been linked to enlargement of the subventricular zone (SVZ) and increased proliferative capacity of basal progenitors (BPs), notably basal radial glia (bRG). The transcription factor Pax6 is known to be highly expressed in primate, but not mouse, BPs. Here, we demonstrate that sustaining Pax6 expression selectively in BP-genic apical radial glia (aRG) and their BP progeny of embryonic mouse neocortex suffices to induce primate-like progenitor behaviour. Specifically, we conditionally expressed Pax6 by in utero electroporation using a novel, Tis21-CreERT2 mouse line. This expression altered aRG cleavage plane orientation to promote bRG generation, increased cell-cycle re-entry of BPs, and ultimately increased upper-layer neuron production. Upper-layer neuron production was also increased in double-transgenic mouse embryos with sustained Pax6 expression in the neurogenic lineage. Strikingly, increased BPs existed not only in the SVZ but also in the intermediate zone of the neocortex of these double-transgenic mouse embryos. In mutant mouse embryos lacking functional Pax6, the proportion of bRG among BPs was reduced. Our data identify specific Pax6 effects in BPs and imply that sustaining this Pax6 function in BPs could be a key aspect of SVZ enlargement and, consequently, the evolutionary expansion of the neocortex.