title: Disrupted-in-Schizophrenia 1 (DISC1) is necessary for the correct migration of cortical interneurons.
abstract: 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.
authors.affiliation: Institut für Allgemeine Zoologie und Tierphysiologie, Universität Jena, 07743 Jena, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Steinecke
authors.forename: Christin
authors.initials: C
authors.lastname: Gampe
authors.forename: Christina
authors.initials: C
authors.lastname: Valkova
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaether
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bolz
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002540:Cerebral Cortex / Q000002:abnormalities / Q000196:embryology* / Q000502:physiology; D005260:Female; D005724:Ganglia / Q000166:cytology / Q000502:physiology; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D061251:Primary Cell Culture; D013687:Telencephalon / Q000002:abnormalities / Q000196:embryology* / Q000502:physiology
chemical_list: C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins