title: Usp9x-deficiency disrupts the morphological development of the postnatal hippocampal dentate gyrus.
abstract: Within the adult mammalian brain, neurogenesis persists within two main discrete locations, the subventricular zone lining the lateral ventricles, and the hippocampal dentate gyrus. Neurogenesis within the adult dentate gyrus contributes to learning and memory, and deficiencies in neurogenesis have been linked to cognitive decline. Neural stem cells within the adult dentate gyrus reside within the subgranular zone (SGZ), and proteins intrinsic to stem cells, and factors within the niche microenvironment, are critical determinants for development and maintenance of this structure. Our understanding of the repertoire of these factors, however, remains limited. The deubiquitylating enzyme USP9X has recently emerged as a mediator of neural stem cell identity. Furthermore, mice lacking Usp9x exhibit a striking reduction in the overall size of the adult dentate gyrus. Here we reveal that the development of the postnatal SGZ is abnormal in mice lacking Usp9x. Usp9x conditional knockout mice exhibit a smaller hippocampus and shortened dentate gyrus blades from as early as P7. Moreover, the analysis of cellular populations within the dentate gyrus revealed reduced stem cell, neuroblast and neuronal numbers and abnormal neuroblast morphology. Collectively, these findings highlight the critical role played by USP9X in the normal morphological development of the postnatal dentate gyrus.
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Oishi
authors.affiliation: The Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD, 4111, Australia.
authors.forename: Susitha
authors.initials: S
authors.lastname: Premarathne
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Tracey J
authors.initials: TJ
authors.lastname: Harvey
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Swati
authors.initials: S
authors.lastname: Iyer
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Chantelle
authors.initials: C
authors.lastname: Dixon
authors.affiliation: Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, QLD, 4077, Australia.|Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Alexander
authors.affiliation: Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, QLD, 4077, Australia.|Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Thomas H J
authors.initials: TH
authors.lastname: Burne
authors.affiliation: The Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD, 4111, Australia.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wood
authors.affiliation: The School of Biomedical Sciences, The University of Queensland, Brisbane, QLD, 4072, Australia.|Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 4072, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Piper
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D002454:Cell Differentiation; D018891:Dentate Gyrus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D010450:Endopeptidases / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D019426:Integrases / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D009929:Organ Size; D043222:Ubiquitin Thiolesterase
chemical_list: C045073:Cre recombinase; D019426:Integrases; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; C404328:Usp9x protein, mouse