TY - JOUR
T1 - Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus
AU - Enomoto, Atsushi
AU - Asai, Naoya
AU - Namba, Takashi
AU - Wang, Yun
AU - Kato, Takuya
AU - Tanaka, Motoki
AU - Tatsumi, Hitoshi
AU - Taya, Shinichiro
AU - Tsuboi, Daisuke
AU - Kuroda, Keisuke
AU - Kaneko, Naoko
AU - Sawamoto, Kazunobu
AU - Miyamoto, Rieko
AU - Jijiwa, Mayumi
AU - Murakumo, Yoshiki
AU - Sokabe, Masahiro
AU - Seki, Tatsunori
AU - Kaibuchi, Kozo
AU - Takahashi, Masahide
N1 - Funding Information:
We gratefully acknowledge A. Sawa (Johns Hopkins University School of Medicine) for providing cDNA for mouse DISC1 and T. Akiyama (Tokyo University, Japan) for providing anti-DISC1 antibody. We thank M. Sugiyama and T. Yoshimura (Nagoya University) for assistance with culturing of hippocampal neurons, and T. Miyata (Nagoya University), T. Shinoda (Aichi Human Service Center), and T. Hikita (Nagoya City University) for helpful discussions. This work was supported by Grants-in-Aid for Global Center of Excellence (GCOE) Research, Scientific Research (A), and Scientific Research on Priority Area ‘Cancer’ (to M.T.); the Program for Improvement of Research Environment for Young Researchers from Special Coordination Funds for Promoting Science and Technology (SCF) (to A.E.) commissioned by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; and the Uehara Memorial Foundation (to A.E.).
PY - 2009/9/24
Y1 - 2009/9/24
N2 - Disrupted-In-Schizophrenia 1 (DISC1), a susceptibility gene for major psychiatric disorders, regulates neuronal migration and differentiation during mammalian brain development. Although roles for DISC1 in postnatal neurogenesis in the dentate gyrus (DG) have recently emerged, it is not known how DISC1 and its interacting proteins govern the migration, positioning, and differentiation of dentate granule cells (DGCs). Here, we report that DISC1 interacts with the actin-binding protein girdin to regulate axonal development. DGCs in girdin-deficient neonatal mice exhibit deficits in axonal sprouting in the cornu ammonis 3 region of the hippocampus. Girdin deficiency, RNA interference-mediated knockdown, and inhibition of the DISC1/girdin interaction lead to overextended migration and mispositioning of the DGCs resulting in profound cytoarchitectural disorganization of the DG. These findings identify girdin as an intrinsic factor in postnatal development of the DG and provide insights into the critical role of the DISC1/girdin interaction in postnatal neurogenesis in the DG.
AB - Disrupted-In-Schizophrenia 1 (DISC1), a susceptibility gene for major psychiatric disorders, regulates neuronal migration and differentiation during mammalian brain development. Although roles for DISC1 in postnatal neurogenesis in the dentate gyrus (DG) have recently emerged, it is not known how DISC1 and its interacting proteins govern the migration, positioning, and differentiation of dentate granule cells (DGCs). Here, we report that DISC1 interacts with the actin-binding protein girdin to regulate axonal development. DGCs in girdin-deficient neonatal mice exhibit deficits in axonal sprouting in the cornu ammonis 3 region of the hippocampus. Girdin deficiency, RNA interference-mediated knockdown, and inhibition of the DISC1/girdin interaction lead to overextended migration and mispositioning of the DGCs resulting in profound cytoarchitectural disorganization of the DG. These findings identify girdin as an intrinsic factor in postnatal development of the DG and provide insights into the critical role of the DISC1/girdin interaction in postnatal neurogenesis in the DG.
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U2 - 10.1016/j.neuron.2009.08.015
DO - 10.1016/j.neuron.2009.08.015
M3 - Article
C2 - 19778507
AN - SCOPUS:70349144020
SN - 0896-6273
VL - 63
SP - 774
EP - 787
JO - Neuron
JF - Neuron
IS - 6
ER -