Disrupted-in-schizophrenia-1 (Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development

Kenji Tomita, Kenichiro Kubo, Kazuhiro Ishii, Kazunori Nakajima

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The hippocampus has a highly ordered structure and is composed of distinct layers. Neuronal migration is an essential part of the process of the layer formation because neurons are primarily generated near the ventricle and must migrate to arrive at their final locat ions during brain development. Impairment of brain development is thought to underlie the etiology of psychiatric disorders. Consistent with this idea, many genetic risk factors for psychiatric disorders play critical roles during brain development. As one example, Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for major psychiatric disorders and plays various roles during neurodevelopment. To examine the role of Disc1 in the hippocampal development, we suppressed expression of Disc1 in the CA1 region of the developing mouse hippocampus by using the RNA interference (RNAi) technology and an in utero electroporation system. Disc1 suppression was found to impair migration of the CA1 pyramidal neurons. This effect was especially apparent while the majority of the transfected neurons were passing through the stratum pyramidale of the developing hippocampus. The migration of neurons was restored by expression of an RNAi-resistant wild-type mouse Disc1, indicating that the migration defect was caused by specific suppression of Disc1. In the mature hippocampus, the migration defect resulted in malposition and disarray of the pyramidal neurons. These findings indicate that Disc1 is required for migration and layer formation by the CA1 pyramidal neurons during hippocampal development.

Original languageEnglish
Article numberddr194
Pages (from-to)2834-2845
Number of pages12
JournalHuman Molecular Genetics
Volume20
Issue number14
DOIs
Publication statusPublished - 2011 Jul

Fingerprint

Pyramidal Cells
Schizophrenia
Hippocampus
Psychiatry
RNA Interference
Neurons
Brain
Electroporation
Ions
Technology

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Disrupted-in-schizophrenia-1 (Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development. / Tomita, Kenji; Kubo, Kenichiro; Ishii, Kazuhiro; Nakajima, Kazunori.

In: Human Molecular Genetics, Vol. 20, No. 14, ddr194, 07.2011, p. 2834-2845.

Research output: Contribution to journalArticle

@article{800b937ad5ea49c8bcdee91c578f7d00,
title = "Disrupted-in-schizophrenia-1 (Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development",
abstract = "The hippocampus has a highly ordered structure and is composed of distinct layers. Neuronal migration is an essential part of the process of the layer formation because neurons are primarily generated near the ventricle and must migrate to arrive at their final locat ions during brain development. Impairment of brain development is thought to underlie the etiology of psychiatric disorders. Consistent with this idea, many genetic risk factors for psychiatric disorders play critical roles during brain development. As one example, Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for major psychiatric disorders and plays various roles during neurodevelopment. To examine the role of Disc1 in the hippocampal development, we suppressed expression of Disc1 in the CA1 region of the developing mouse hippocampus by using the RNA interference (RNAi) technology and an in utero electroporation system. Disc1 suppression was found to impair migration of the CA1 pyramidal neurons. This effect was especially apparent while the majority of the transfected neurons were passing through the stratum pyramidale of the developing hippocampus. The migration of neurons was restored by expression of an RNAi-resistant wild-type mouse Disc1, indicating that the migration defect was caused by specific suppression of Disc1. In the mature hippocampus, the migration defect resulted in malposition and disarray of the pyramidal neurons. These findings indicate that Disc1 is required for migration and layer formation by the CA1 pyramidal neurons during hippocampal development.",
author = "Kenji Tomita and Kenichiro Kubo and Kazuhiro Ishii and Kazunori Nakajima",
year = "2011",
month = "7",
doi = "10.1093/hmg/ddr194",
language = "English",
volume = "20",
pages = "2834--2845",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "14",

}

TY - JOUR

T1 - Disrupted-in-schizophrenia-1 (Disc1) is necessary for migration of the pyramidal neurons during mouse hippocampal development

AU - Tomita, Kenji

AU - Kubo, Kenichiro

AU - Ishii, Kazuhiro

AU - Nakajima, Kazunori

PY - 2011/7

Y1 - 2011/7

N2 - The hippocampus has a highly ordered structure and is composed of distinct layers. Neuronal migration is an essential part of the process of the layer formation because neurons are primarily generated near the ventricle and must migrate to arrive at their final locat ions during brain development. Impairment of brain development is thought to underlie the etiology of psychiatric disorders. Consistent with this idea, many genetic risk factors for psychiatric disorders play critical roles during brain development. As one example, Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for major psychiatric disorders and plays various roles during neurodevelopment. To examine the role of Disc1 in the hippocampal development, we suppressed expression of Disc1 in the CA1 region of the developing mouse hippocampus by using the RNA interference (RNAi) technology and an in utero electroporation system. Disc1 suppression was found to impair migration of the CA1 pyramidal neurons. This effect was especially apparent while the majority of the transfected neurons were passing through the stratum pyramidale of the developing hippocampus. The migration of neurons was restored by expression of an RNAi-resistant wild-type mouse Disc1, indicating that the migration defect was caused by specific suppression of Disc1. In the mature hippocampus, the migration defect resulted in malposition and disarray of the pyramidal neurons. These findings indicate that Disc1 is required for migration and layer formation by the CA1 pyramidal neurons during hippocampal development.

AB - The hippocampus has a highly ordered structure and is composed of distinct layers. Neuronal migration is an essential part of the process of the layer formation because neurons are primarily generated near the ventricle and must migrate to arrive at their final locat ions during brain development. Impairment of brain development is thought to underlie the etiology of psychiatric disorders. Consistent with this idea, many genetic risk factors for psychiatric disorders play critical roles during brain development. As one example, Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for major psychiatric disorders and plays various roles during neurodevelopment. To examine the role of Disc1 in the hippocampal development, we suppressed expression of Disc1 in the CA1 region of the developing mouse hippocampus by using the RNA interference (RNAi) technology and an in utero electroporation system. Disc1 suppression was found to impair migration of the CA1 pyramidal neurons. This effect was especially apparent while the majority of the transfected neurons were passing through the stratum pyramidale of the developing hippocampus. The migration of neurons was restored by expression of an RNAi-resistant wild-type mouse Disc1, indicating that the migration defect was caused by specific suppression of Disc1. In the mature hippocampus, the migration defect resulted in malposition and disarray of the pyramidal neurons. These findings indicate that Disc1 is required for migration and layer formation by the CA1 pyramidal neurons during hippocampal development.

UR - http://www.scopus.com/inward/record.url?scp=79959781594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79959781594&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddr194

DO - 10.1093/hmg/ddr194

M3 - Article

VL - 20

SP - 2834

EP - 2845

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 14

M1 - ddr194

ER -