title: Nitric oxide synthase 1 adaptor protein, a protein implicated in schizophrenia, controls radial migration of cortical neurons.
abstract: BACKGROUND
  Where a neuron is positioned in the brain during development determines neuronal circuitry and information processing needed for normal brain function. When aberrations in this process occur, cognitive disorders may result. Patients diagnosed with schizophrenia have been reported to show altered neuronal connectivity and heterotopias. To elucidate pathways by which this process occurs and become aberrant, we have chosen to study the long isoform of nitric oxide synthase 1 adaptor protein (NOS1AP), a protein encoded by a susceptibility gene for schizophrenia.
  
  
  METHODS
  To determine whether NOS1AP plays a role in cortical patterning, we knocked down or co-overexpressed NOS1AP and a green fluorescent protein or red fluorescent protein (TagRFP) reporter in neuronal progenitor cells of the embryonic rat neocortex using in utero electroporation. We analyzed sections of cortex (ventricular zone, intermediate zone, and cortical plate [CP]) containing green fluorescent protein or red fluorescent protein TagRFP positive cells and counted the percentage of positive cells that migrated to each region from at least three rats for each condition.
  
  
  RESULTS
  NOS1AP overexpression disrupts neuronal migration, resulting in increased cells in intermediate zone and less cells in CP, and decreases dendritogenesis. Knockdown results in increased migration, with more cells reaching the CP. The phosphotyrosine binding region, but not the PDZ-binding motif, is necessary for NOS1AP function. Amino acids 181 to 307, which are sufficient for NOS1AP-mediated decreases in dendrite number, have no effect on migration.
  
  
  CONCLUSIONS
  Our studies show for the first time a critical role for the schizophrenia-associated gene NOS1AP in cortical patterning, which may contribute to underlying pathophysiology seen in schizophrenia.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey; Neurophotonics Laboratory, Paris Descartes University, Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Carrel
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey; Molecular Biosciences Graduate Program Rutgers, the State University of New Jersey, Piscataway, New Jersey.
authors.forename: Kristina
authors.initials: K
authors.lastname: Hernandez
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey; Molecular Biosciences Graduate Program Rutgers, the State University of New Jersey, Piscataway, New Jersey.
authors.forename: Munjin
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey.
authors.forename: Christine
authors.initials: C
authors.lastname: Mau
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey.
authors.forename: Meera P
authors.initials: MP
authors.lastname: Trivedi
authors.affiliation: Department of Genetics, Rutgers, the State University of New Jersey, Piscataway, New Jersey.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Brzustowicz
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey. Electronic address: firestein@biology.rutgers.edu.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Firestein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002465:Cell Movement / Q000235:genetics*; D002522:Chlorocebus aethiops; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation / Q000235:genetics; D019579:Neocortex / Q000166:cytology*; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D054731:PDZ Domains / Q000235:genetics; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D014162:Transfection; D000097573:Red Fluorescent Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D034741:RNA, Small Interfering; D000097573:Red Fluorescent Protein; C488082:NOS1AP protein, rat
keywords: Cortical development; Cortical neuron migration; NOS1AP; Rodent model; Schizophrenia; in utero Electroporation