Roles of Disrupted-In-Schizophrenia 1-Interacting Protein Girdin in Postnatal Development of the Dentate Gyrus

Atsushi Enomoto, Naoya Asai, Takashi Namba, Yun Wang, Takuya Kato, Motoki Tanaka, Hitoshi Tatsumi, Shinichiro Taya, Daisuke Tsuboi, Keisuke Kuroda, Naoko Kaneko, Kazunobu Sawamoto, Rieko Miyamoto, Mayumi Jijiwa, Yoshiki Murakumo, Masahiro Sokabe, Tatsunori Seki, Kozo Kaibuchi, Masahide Takahashi

研究成果: Article査読

144 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)774-787
ページ数14
ジャーナルNeuron
63
6
DOI
出版ステータスPublished - 24-09-2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)

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