Disc1 regulates granule cell migration in the developing hippocampus.

Journal Article (Journal Article)

Schizophrenia is a severely debilitating psychiatric disease that is hypothesized to have its roots in neurodevelopment. Although the precise neuropathology underlying schizophrenia has remained elusive, there are consistent reports of abnormalities in several brain areas. Chief among these is the hippocampus, an area which has displayed both structural and functional abnormalities in many schizophrenic patients. In order to better understand how disruption of hippocampal development may contribute to the etiology of psychiatric disease, we investigated the function of a highly promising schizophrenia susceptibility gene, DISC1 (Disrupted-In-Schizophrenia 1), in the development of the hippocampus. DISC1 is strongly expressed in the hippocampus from its early development through adulthood and has been implicated in hippocampal structure and function in human studies. However, its precise role in the development of the hippocampus is not yet known. Here, we show that in utero electroporation of Disc1 shRNA into the developing mouse hippocampus hinders the migration of dentate gyrus granule cells. Intriguingly, Disc1 knockdown does not affect the migration of CA1 pyramidal neurons, suggesting that Disc1's role in regulating neuronal migration is spatially restricted within the hippocampus. These findings support the idea that DISC1 abnormalities that contribute to the onset of schizophrenia may do so through their influences on hippocampal development.

Full Text

Duke Authors

Cited Authors

  • Meyer, KD; Morris, JA

Published Date

  • September 1, 2009

Published In

Volume / Issue

  • 18 / 17

Start / End Page

  • 3286 - 3297

PubMed ID

  • 19502360

Pubmed Central ID

  • PMC2722990

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddp266


  • eng

Conference Location

  • England