Disrupted-in-Schizophrenia 1 (DISC1) is necessary for the correct migration of cortical interneurons

Disrupted-in-Schizophrenia 1 (DISC1) is a prominent susceptibility gene for major psychiatric disorders. Previous work indicated that DISC1 plays an important role during neuronal proliferation and differentiation in the cerebral cortex and that it affects the positioning of radial migrating pyramid...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of neuroscience 2012-01, Vol.32 (2), p.738-745
Main Authors: Steinecke, André, Gampe, Christin, Valkova, Christina, Kaether, Christoph, Bolz, Jürgen
Format: Article
Language:English
Subjects:
Animals
Cell Movement - physiology
Cerebral Cortex - abnormalities
Cerebral Cortex - embryology
Cerebral Cortex - physiology
Female
Ganglia - cytology
Ganglia - physiology
Interneurons - cytology
Interneurons - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - physiology
NIH 3T3 Cells
Organ Culture Techniques
Pregnancy
Primary Cell Culture
Telencephalon - abnormalities
Telencephalon - embryology
Telencephalon - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Disrupted-in-Schizophrenia 1 (DISC1) is a prominent susceptibility gene for major psychiatric disorders. Previous work indicated that DISC1 plays an important role during neuronal proliferation and differentiation in the cerebral cortex and that it affects the positioning of radial migrating pyramidal neurons. Here we show that in mice, DISC1 is necessary for the migration of the cortical interneurons generated in the medial ganglionic eminence (MGE). RT-PCR, in situ hybridizations, and immunocytochemical data revealed expression of DISC1 transcripts and protein in MGE-derived cells. To study the possible functional role of DISC1 during tangential migration, we performed in utero and ex utero electroporation to suppress DISC1 in the MGE in vivo and in vitro. Results indicate that after DISC1 knockdown, the proportion of tangentially migrating MGE neurons that reached their cortical target was strongly reduced. In addition, there were profound alterations in the morphology of DISC1-deficient neurons, which exhibited longer and less branched leading processes than control cells. These findings provide a possible link between clinical studies reporting alterations of cortical interneurons in schizophrenic patients and the current notion of schizophrenia as a neurodevelopmental disorder.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.5036-11.2012