title: Structure-function integrity of the adult hippocampus depends on the transcription factor Bcl11b/Ctip2.
abstract: The dentate gyrus is one of the only two brain regions where adult neurogenesis occurs. Throughout life, cells of the neuronal stem cell niche undergo proliferation, differentiation and integration into the hippocampal neural circuitry. Ongoing adult neurogenesis is a prerequisite for the maintenance of adult hippocampal functionality. Bcl11b, a zinc finger transcription factor, is expressed by postmitotic granule cells in the developing as well as adult dentate gyrus. We previously showed a critical role of Bcl11b for hippocampal development. Whether Bcl11b is also required for adult hippocampal functions has not been investigated. Using a tetracycline-dependent inducible mouse model under the control of the forebrain-specific CaMKIIα promoter, we show here that the adult expression of Bcl11b is essential for survival, differentiation and functional integration of adult-born granule cell neurons. In addition, Bcl11b is required for survival of pre-existing mature neurons. Consequently, loss of Bcl11b expression selectively in the adult hippocampus results in impaired spatial working memory. Together, our data uncover for the first time a specific role of Bcl11b in adult hippocampal neurogenesis and function.
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Ulm.
authors.forename: R
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Ulm.|Institute of Pathology and Neuropathology, University of Tübingen, Tübingen.
authors.forename: L
authors.initials: L
authors.lastname: Baumann
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Ulm.
authors.forename: J
authors.initials: J
authors.lastname: Fischer
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Ulm.|Institute of Biochemistry and Molecular Biology, Ulm University, Ulm, Germany.
authors.forename: F A
authors.initials: FA
authors.lastname: Seigfried
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Ulm.
authors.forename: E
authors.initials: E
authors.lastname: De Bruyckere
authors.affiliation: Wellcome Trust Sanger Institute, Cambridge, UK.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.affiliation: Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
authors.affiliation: Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.affiliation: Institute of Anatomy, Otto-von-Guericke-University, Magdeburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Schwegler
authors.affiliation: Institute of Molecular and Cellular Anatomy, Ulm University, Ulm.
authors.forename: S
authors.initials: S
authors.lastname: Britsch
mesh_terms: D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D018891:Dentate Gyrus / Q000378:metabolism; D015870:Gene Expression; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013329:Structure-Activity Relationship; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: C511143:Bcl11b protein, mouse; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins
keywords: Adult neurogenesis; Bcl11b; dentate gyrus; hippocampus; spatial memory