title: NFIX regulates neural progenitor cell differentiation during hippocampal morphogenesis.
abstract: Neural progenitor cells have the ability to give rise to neurons and glia in the embryonic, postnatal and adult brain. During development, the program regulating whether these cells divide and self-renew or exit the cell cycle and differentiate is tightly controlled, and imbalances to the normal trajectory of this process can lead to severe functional consequences. However, our understanding of the molecular regulation of these fundamental events remains limited. Moreover, processes underpinning development of the postnatal neurogenic niches within the cortex remain poorly defined. Here, we demonstrate that Nuclear factor one X (NFIX) is expressed by neural progenitor cells within the embryonic hippocampus, and that progenitor cell differentiation is delayed within Nfix(-/-) mice. Moreover, we reveal that the morphology of the dentate gyrus in postnatal Nfix(-/-) mice is abnormal, with fewer subgranular zone neural progenitor cells being generated in the absence of this transcription factor. Mechanistically, we demonstrate that the progenitor cell maintenance factor Sry-related HMG box 9 (SOX9) is upregulated in the hippocampus of Nfix(-/-) mice and demonstrate that NFIX can repress Sox9 promoter-driven transcription. Collectively, our findings demonstrate that NFIX plays a central role in hippocampal morphogenesis, regulating the formation of neuronal and glial populations within this structure.
authors.affiliation: The School of Biomedical Sciences.
authors.forename: Yee Hsieh Evelyn
authors.initials: YH
authors.lastname: Heng
authors.forename: Robert C
authors.initials: RC
authors.lastname: McLeay
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Harvey
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Smith
authors.forename: Guy
authors.initials: G
authors.lastname: Barry
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cato
authors.forename: Céline
authors.initials: C
authors.lastname: Plachez
authors.forename: Erica
authors.initials: E
authors.lastname: Little
authors.forename: Sharon
authors.initials: S
authors.lastname: Mason
authors.forename: Chantelle
authors.initials: C
authors.lastname: Dixon
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Bailey
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Richards
authors.forename: Michael
authors.initials: M
authors.lastname: Piper
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D004396:Coloring Agents; D019295:Computational Biology; D018891:Dentate Gyrus / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D018274:Electroporation; D005260:Female; D006416:Hematoxylin; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D051839:NFI Transcription Factors / Q000235:genetics / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D016612:Paraffin Embedding; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D004396:Coloring Agents; D051839:NFI Transcription Factors; C497650:Nfix protein, mouse; D008156:Luciferases; D006416:Hematoxylin