title: Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via β-catenin.
abstract: Breast carcinoma amplified sequence 2 (BCAS2) is a core component of the hPrP19 complex that controls RNA splicing. Here, we performed an exon array assay and showed that β-catenin is a target of BCAS2 splicing regulation. The regulation of dendrite growth and morphology by β-catenin is well documented. Therefore, we generated conditional knockout (cKO) mice to eliminate the BCAS2 expression in the forebrain to investigate the role of BCAS2 in dendrite growth. BCAS2 cKO mice showed a microcephaly-like phenotype with a reduced volume in the dentate gyrus (DG) and low levels of learning and memory, as evaluated using Morris water maze analysis and passive avoidance, respectively. Golgi staining revealed shorter dendrites, less dendritic complexity and decreased spine density in the DG of BCAS2 cKO mice. Moreover, the cKO mice displayed a short dendrite length in newborn neurons labeled by DCX, a marker of immature neurons, and BrdU incorporation. To further examine the mechanism underlying BCAS2-mediated dendritic malformation, we overexpressed β-catenin in BCAS2-depleted primary neurons and found that the dendritic growth was restored. In summary, BCAS2 is an upstream regulator of β-catenin gene expression and plays a role in dendrite growth at least partly through β-catenin.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Chu-Wei
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Yi-Rou
authors.initials: YR
authors.lastname: Lin
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Po-Han
authors.initials: PH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Chou
authors.affiliation: Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Lee
authors.affiliation: Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.|Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: June-Tai
authors.initials: JT
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D060825:Cognitive Dysfunction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000378:metabolism* / Q000473:pathology*; D000089662:Doublecortin Protein; D005091:Exons; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D018345:Mice, Knockout; D008831:Microcephaly / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016548:Prosencephalon / Q000002:abnormalities* / Q000378:metabolism*; D012326:RNA Splicing; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C000605455:BCAS2 protein, mouse; C495267:CTNNB1 protein, mouse; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D009363:Neoplasm Proteins; D051176:beta Catenin