Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain

Xin Duan, Jay H. Chang, Shaoyu Ge, Regina L. Faulkner, Ju Young Kim, Yasuji Kitabatake, Xiao bo Liu, Chih Hao Yang, J. Dedrick Jordan, Dengke K. Ma, Cindy Y. Liu, Sundar Ganesan, Hwai-Jong Cheng, Guo li Ming, Bai Lu, Hongjun Song

Research output: Contribution to journalArticle

471 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1146-1158
Number of pages13
JournalCell
Volume130
Issue number6
DOIs
StatePublished - Sep 21 2007

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Neurons
Brain
Schizophrenia
Neurogenesis
Genes
Stem cells
Adult Stem Cells
Neural Stem Cells
Synapses
Down-Regulation

Keywords

  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Duan, X., Chang, J. H., Ge, S., Faulkner, R. L., Kim, J. Y., Kitabatake, Y., ... Song, H. (2007). Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain. Cell, 130(6), 1146-1158. https://doi.org/10.1016/j.cell.2007.07.010

Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain. / Duan, Xin; Chang, Jay H.; Ge, Shaoyu; Faulkner, Regina L.; Kim, Ju Young; Kitabatake, Yasuji; Liu, Xiao bo; Yang, Chih Hao; Jordan, J. Dedrick; Ma, Dengke K.; Liu, Cindy Y.; Ganesan, Sundar; Cheng, Hwai-Jong; Ming, Guo li; Lu, Bai; Song, Hongjun.

In: Cell, Vol. 130, No. 6, 21.09.2007, p. 1146-1158.

Research output: Contribution to journalArticle

Duan, X, Chang, JH, Ge, S, Faulkner, RL, Kim, JY, Kitabatake, Y, Liu, XB, Yang, CH, Jordan, JD, Ma, DK, Liu, CY, Ganesan, S, Cheng, H-J, Ming, GL, Lu, B & Song, H 2007, 'Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain', Cell, vol. 130, no. 6, pp. 1146-1158. https://doi.org/10.1016/j.cell.2007.07.010
Duan X, Chang JH, Ge S, Faulkner RL, Kim JY, Kitabatake Y et al. Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain. Cell. 2007 Sep 21;130(6):1146-1158. https://doi.org/10.1016/j.cell.2007.07.010
Duan, Xin ; Chang, Jay H. ; Ge, Shaoyu ; Faulkner, Regina L. ; Kim, Ju Young ; Kitabatake, Yasuji ; Liu, Xiao bo ; Yang, Chih Hao ; Jordan, J. Dedrick ; Ma, Dengke K. ; Liu, Cindy Y. ; Ganesan, Sundar ; Cheng, Hwai-Jong ; Ming, Guo li ; Lu, Bai ; Song, Hongjun. / Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain. In: Cell. 2007 ; Vol. 130, No. 6. pp. 1146-1158.
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