Roles of disrupted-in-schizophrenia 1-interacting protein girdin in postnatal development of the dentate gyrus.
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.
Department of Pathology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. enomoto@iar.nagoya-u.ac.jp
Atsushi
A
Enomoto
Naoya
N
Asai
Takashi
T
Namba
Yun
Y
Wang
Takuya
T
Kato
Motoki
M
Tanaka
Hitoshi
H
Tatsumi
Shinichiro
S
Taya
Daisuke
D
Tsuboi
Keisuke
K
Kuroda
Naoko
N
Kaneko
Kazunobu
K
Sawamoto
Rieko
R
Miyamoto
Mayumi
M
Jijiwa
Yoshiki
Y
Murakumo
Masahiro
M
Sokabe
Tatsunori
T
Seki
Kozo
K
Kaibuchi
Masahide
M
Takahashi
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018891:Dentate Gyrus / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D014162:Transfection / Q000379:methods; D033921:Vesicular Transport Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D001973:Bromodeoxyuridine; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D033921:Vesicular Transport Proteins; C498794:Disc1 protein, mouse; C527550:Ccdc88a protein, mouse