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Human Molecular Genetics Advance Access originally published online on June 5, 2009
Human Molecular Genetics 2009 18(17):3286-3297; doi:10.1093/hmg/ddp266
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Disc1 regulates granule cell migration in the developing hippocampus

Kate D. Meyer1,2 and Jill A. Morris1,2,*

1 Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA 2 Human Molecular Genetics Program, Children's Memorial Research Center, Chicago, IL 60614, USA

* To whom correspondence should be addressed at: Children's Memorial Research Center, 2300 Children's Plaza, PO Box 211, Chicago, IL 60614, USA. Tel: +1 7737556351; Fax: +1 7737556345; Email: j-morris4{at}northwestern.edu

Received March 26, 2009; Accepted June 3, 2009

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.


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