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Tomita K, Kubo K, Ishii K, Nakajima K. Disrupted-in-Schizophrenia-1 (Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development. Hum Mol Genet . 2011 Jul 15 ; 20(14):2834-45. PubMed Abstract

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Comment by:  Albert H. C. Wong
Submitted 1 June 2011 Posted 1 June 2011

This paper reports that reduced expression of DISC1 during late embryonic development (E15) impairs the migration of hippocampal pyramidal neurons into CA1, and disrupts the alignment and position of these neurons. Using in utero electroporation of RNAi against endogenous DISC1, the authors were able to disrupt hippocampal development and rescue the anatomical defects by expressing an RNAi-resistant DISC1. This paper provides further information about the important role of DISC1 in neuron migration during brain development, and is consistent with a number of similar studies of the cortex. Neuron migration problems have long been hypothesized to underlie the histopathological abnormalities seen in postmortem brain from patients with schizophrenia. This study and other recent work make it increasingly plausible to speculate that schizophrenia-associated variants in the DISC1 gene might affect the development of the cortex and hippocampus in patients with the disease.

It would be interesting to know the behavioral effects of DISC1 RNAi knockdown in the hippocampus, and to...  Read more

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