title: PAX6 does not regulate Nfia and Nfib expression during neocortical development.
abstract: The Nuclear factor I (NFI) family of transcription factors regulates proliferation and differentiation throughout the developing central nervous system. In the developing telencephalon of humans and mice, reduced Nfi expression is associated with agenesis of the corpus callosum and other neurodevelopmental defects. Currently, little is known about how Nfi expression is regulated during early telencephalic development. PAX6, a transcription factor important for telencephalic development, has been proposed as an upstream regulator of Nfi expression in the neocortex. Here we demonstrate that, in the developing neocortex of mice, NFIA and NFIB are endogenously expressed in gradients with high caudo-medial to low rostro-lateral expression and are most highly expressed in the cortical plate. We found that this expression pattern deviates from that of PAX6, suggesting that PAX6 does not drive Nfi expression. This is supported by in vitro reporter assays showing that PAX6 over-expression does not regulate Nfi promoter activity. Similarly, we also found that in the Pax6 Small Eye mutant, no changes in Nfi mRNA or protein expression are observed in the neocortical ventricular zone where PAX6 and the NFIs are expressed. Together these data demonstrate that in mice, PAX6 is not a transcriptional activator of Nfi expression during neocortical development.
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia.
authors.forename: Jens
authors.initials: J
authors.lastname: Bunt
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia.
authors.forename: Jonathan W C
authors.initials: JW
authors.lastname: Lim
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia.
authors.forename: Sharon
authors.initials: S
authors.lastname: Mason
authors.affiliation: 1] Queensland Brain Institute, The University of Queensland, Brisbane, 4072, Australia [2] The School of Biomedical Sciences, The University of Queensland, Brisbane, 4072, Australia.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D051839:NFI Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D019579:Neocortex / Q000254:growth & development*; D009457:Neuroglia / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D051839:NFI Transcription Factors; C497646:Nfia protein, mouse; C484683:Nfib protein, mouse; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins