title: Transcriptional regulation of intermediate progenitor cell generation during hippocampal development.
abstract: During forebrain development, radial glia generate neurons through the production of intermediate progenitor cells (IPCs). The production of IPCs is a central tenet underlying the generation of the appropriate number of cortical neurons, but the transcriptional logic underpinning this process remains poorly defined. Here, we examined IPC production using mice lacking the transcription factor nuclear factor I/X (Nfix). We show that Nfix deficiency delays IPC production and prolongs the neurogenic window, resulting in an increased number of neurons in the postnatal forebrain. Loss of additional Nfi alleles (Nfib) resulted in a severe delay in IPC generation while, conversely, overexpression of NFIX led to precocious IPC generation. Mechanistically, analyses of microarray and ChIP-seq datasets, coupled with the investigation of spindle orientation during radial glial cell division, revealed that NFIX promotes the generation of IPCs via the transcriptional upregulation of inscuteable (Insc). These data thereby provide novel insights into the mechanisms controlling the timely transition of radial glia into IPCs during forebrain development.
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Harris
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.|Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Oressia
authors.initials: O
authors.lastname: Zalucki
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Ilan
authors.initials: I
authors.lastname: Gobius
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Hannah
authors.initials: H
authors.lastname: McDonald
authors.affiliation: Department of Biochemistry, Program in Genetics, Genomics and Bioinformatics, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Osinki
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Harvey
authors.affiliation: The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Essebier
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Diana
authors.initials: D
authors.lastname: Vidovic
authors.affiliation: The Harry Perkins Institute of Medical Research, Crawley, Western Australia 6009, Australia.|The Centre for Medical Research, Crawley, Western Australia 6009, Australia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gladwyn-Ng
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.|Queensland Centre for Mental Health Research, Wacol 4076, Australia.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Burne
authors.affiliation: The Harry Perkins Institute of Medical Research, Crawley, Western Australia 6009, Australia.|The Centre for Medical Research, Crawley, Western Australia 6009, Australia.
authors.forename: Julian I
authors.initials: JI
authors.lastname: Heng
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia.|Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.affiliation: Department of Biochemistry, Program in Genetics, Genomics and Bioinformatics, Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane 4072, Australia m.piper@uq.edu.au.|Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia.
authors.forename: Michael
authors.identifier: 0000-0002-6759-2560
authors.initials: M
authors.lastname: Piper
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D051839:NFI Transcription Factors / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D051839:NFI Transcription Factors; C484683:Nfib protein, mouse; C497650:Nfix protein, mouse; C561632:inscuteable protein, mouse
keywords: Hippocampus; Intermediate progenitor cell; Mouse; NFIX