title: NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche.
abstract: Transcription factors of the nuclear factor one (NFI) family play a pivotal role in the development of the nervous system. One member, NFIX, regulates the development of the neocortex, hippocampus, and cerebellum. Postnatal Nfix(-/-) mice also display abnormalities within the subventricular zone (SVZ) lining the lateral ventricles, a region of the brain comprising a neurogenic niche that provides ongoing neurogenesis throughout life. Specifically, Nfix(-/-) mice exhibit more PAX6-expressing progenitor cells within the SVZ. However, the mechanism underlying the development of this phenotype remains undefined. Here, we reveal that NFIX contributes to multiple facets of SVZ development. Postnatal Nfix(-/-) mice exhibit increased levels of proliferation within the SVZ, both in vivo and in vitro as assessed by a neurosphere assay. Furthermore, we show that the migration of SVZ-derived neuroblasts to the olfactory bulb is impaired, and that the olfactory bulbs of postnatal Nfix(-/-) mice are smaller. We also demonstrate that gliogenesis within the rostral migratory stream is delayed in the absence of Nfix, and reveal that Gdnf (glial-derived neurotrophic factor), a known attractant for SVZ-derived neuroblasts, is a target for transcriptional activation by NFIX. Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche.
authors.affiliation: The School of Biomedical Sciences.
authors.forename: Yee Hsieh Evelyn
authors.initials: YH
authors.lastname: Heng
authors.affiliation: Department of Biochemistry, Programs in Neuroscience and Genetics, Genomics & Bioinformatics, Developmental Genomics Group, New York State Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: The School of Biomedical Sciences.
authors.forename: Lachlan
authors.initials: L
authors.lastname: Harris
authors.affiliation: The School of Biomedical Sciences.
authors.forename: Tracey
authors.initials: T
authors.lastname: Harvey
authors.affiliation: The School of Biomedical Sciences.
authors.forename: Aaron
authors.initials: A
authors.lastname: Smith
authors.affiliation: The School of Biomedical Sciences.
authors.forename: Elise
authors.initials: E
authors.lastname: Horne
authors.affiliation: Division of Molecular Neurobiology, MRC-National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Ben
authors.initials: B
authors.lastname: Martynoga
authors.affiliation: Division of Molecular Neurobiology, MRC-National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Jimena
authors.initials: J
authors.lastname: Andersen
authors.affiliation: Division of Molecular Neurobiology, MRC-National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: Angeliki
authors.initials: A
authors.lastname: Achimastou
authors.affiliation: The School of Biomedical Sciences.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cato
authors.affiliation: The School of Biomedical Sciences Queensland Brain Institute.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.affiliation: Department of Biochemistry, Programs in Neuroscience and Genetics, Genomics & Bioinformatics, Developmental Genomics Group, New York State 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: MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Giles S
authors.initials: GS
authors.lastname: Yeo
authors.affiliation: Division of Molecular Neurobiology, MRC-National Institute for Medical Research, London NW7 1AA, UK.
authors.forename: François
authors.initials: F
authors.lastname: Guillemot
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Bailey
authors.affiliation: The School of Biomedical Sciences Queensland Brain Institute.
authors.forename: Michael
authors.initials: M
authors.lastname: Piper
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D007395:Interneurons / Q000502:physiology; D020547:Lateral Ventricles / Q000196:embryology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051839:NFI Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis; D009457:Neuroglia / Q000502:physiology; D009830:Olfactory Bulb / Q000196:embryology / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D051839:NFI Transcription Factors; C497650:Nfix protein, mouse
keywords: neuroblast; nuclear factor one X; olfactory bulb; rostral migratory stream; subventricular zone