title: Ablation of BAF170 in Developing and Postnatal Dentate Gyrus Affects Neural Stem Cell Proliferation, Differentiation, and Learning.
abstract: The BAF chromatin remodeling complex plays an essential role in brain development. However its function in postnatal neurogenesis in hippocampus is still unknown. Here, we show that in postnatal dentate gyrus (DG), the BAF170 subunit of the complex is expressed in radial glial-like (RGL) progenitors and in cell types involved in subsequent steps of adult neurogenesis including mature astrocytes. Conditional deletion of BAF170 during cortical late neurogenesis as well as during adult brain neurogenesis depletes the pool of RGL cells in DG, and promotes terminal astrocyte differentiation. These derangements are accompanied by distinct behavioral deficits, as reflected by an impaired accuracy of place responding in the Morris water maze test, during both hidden platform as well as reversal learning. Inducible deletion of BAF170 in DG during adult brain neurogenesis resulted in mild spatial learning deficits, having a more pronounced effect on spatial learning during the reversal test. These findings demonstrate involvement of BAF170-dependent chromatin remodeling in hippocampal neurogenesis and cognition and suggest a specific role of adult neurogenesis in DG in adaptive behavior.
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August University Göttingen, Göttingen, Germany. tran.tuoc@med.uni-goettingen.de.|Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany. tran.tuoc@med.uni-goettingen.de.|DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. tran.tuoc@med.uni-goettingen.de.
authors.forename: Tran
authors.initials: T
authors.lastname: Tuoc
authors.affiliation: DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. dere@em.mpg.de.|Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany. dere@em.mpg.de.
authors.forename: Ekrem
authors.initials: E
authors.lastname: Dere
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Radyushkin
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August University Göttingen, Göttingen, Germany.
authors.forename: Linh
authors.initials: L
authors.lastname: Pham
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August University Göttingen, Göttingen, Germany.
authors.forename: Huong
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.|Department of Anatomy, Histology and Embryology, Medical University of Varna, Varna, Bulgaria.
authors.forename: Anton B
authors.initials: AB
authors.lastname: Tonchev
authors.affiliation: Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Ronnenberg
authors.affiliation: Division of Stem Cell Biology Research, Department of Developmental and Stem Cell Biology, Cancer Center, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA, 91010, USA.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institute of Neuroanatomy, University Medical Center, Georg-August University Göttingen, Göttingen, Germany.|DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Jochen F
authors.initials: JF
authors.lastname: Staiger
authors.affiliation: DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.|Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Hannelore
authors.initials: H
authors.lastname: Ehrenreich
authors.affiliation: Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany. astoyko@gwdg.de.|DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. astoyko@gwdg.de.
authors.forename: Anastassia
authors.initials: A
authors.lastname: Stoykova
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency* / Q000378:metabolism; D004268:DNA-Binding Proteins; D018891:Dentate Gyrus / Q000166:cytology* / Q000254:growth & development*; D019426:Integrases / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology; D014157:Transcription Factors
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D064231:Nestin; C587872:Smarcc2 protein, mouse; D014157:Transcription Factors; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases
keywords: Adult neuronal stem cells neurogenesis; Astrogenesis; BAF170; Hippocampus; Learning and memory; SWI/SNF complex