Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Duan, X; Chang, JH; Ge, S; Faulkner, RL; Kim, JY; Kitabatake, Y; Liu, X-B; Yang, C-H; Jordan, JD; Ma, DK; Liu, CY; Ganesan, S; Cheng, H-J; Ming, G-L; Lu, B; Song, H

Published Date

  • September 21, 2007

Published In

Volume / Issue

  • 130 / 6

Start / End Page

  • 1146 - 1158

PubMed ID

  • 17825401

Pubmed Central ID

  • 17825401

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2007.07.010

Language

  • eng

Conference Location

  • United States