title: Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.
abstract: Adult neurogenesis occurs throughout life in discrete regions of the adult mammalian brain. Little is known about the mechanism governing the sequential developmental process that leads to integration of new neurons from adult neural stem cells into the existing circuitry. Here, we investigated roles of Disrupted-In-Schizophrenia 1 (DISC1), a schizophrenia susceptibility gene, in adult hippocampal neurogenesis. Unexpectedly, downregulation of DISC1 leads to accelerated neuronal integration, resulting in aberrant morphological development and mispositioning of new dentate granule cells in a cell-autonomous fashion. Functionally, newborn neurons with DISC1 knockdown exhibit enhanced excitability and accelerated dendritic development and synapse formation. Furthermore, DISC1 cooperates with its binding partner NDEL1 in regulating adult neurogenesis. Taken together, our study identifies DISC1 as a key regulator that orchestrates the tempo of functional neuronal integration in the adult brain and demonstrates essential roles of a susceptibility gene for major mental illness in neuronal development, including adult neurogenesis.
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.forename: Jay H
authors.initials: JH
authors.lastname: Chang
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Ge
authors.forename: Regina L
authors.initials: RL
authors.lastname: Faulkner
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Kitabatake
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Liu
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Yang
authors.forename: J Dedrick
authors.initials: JD
authors.lastname: Jordan
authors.forename: Dengke K
authors.initials: DK
authors.lastname: Ma
authors.forename: Cindy Y
authors.initials: CY
authors.lastname: Liu
authors.forename: Sundar
authors.initials: S
authors.lastname: Ganesan
authors.forename: Hwai-Jong
authors.initials: HJ
authors.lastname: Cheng
authors.forename: Guo-li
authors.initials: GL
authors.lastname: Ming
authors.forename: Bai
authors.initials: B
authors.lastname: Lu
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
mesh_terms: D000200:Action Potentials; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D048429:Cell Size; D003712:Dendrites / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D005822:Genetic Vectors; D005838:Genotype; D006624:Hippocampus / Q000196:embryology / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission; D013997:Time Factors