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Modelling disrupted-in-schizophrenia 1 loss of function in human neural progenitor cells: tools for molecular studies of human neurodevelopment and neuropsychiatric disorders

Molecular Psychiatry volume 15, pages 672–675 (2010)Cite this article

Human neural progenitor cells (NPCs) offer a new strategy for de novo modelling of neurodevelopment and neuropsychiatric disease.1 They can be derived from numerous stem cell types including embryonic and adult stem cells, or isolated from neurogenic tissues of the human central nervous system. As lineage-restricted cells, NPCs are self-renewing and easily differentiated to neurons, astrocytes and oligodendrocytes using methods that emulate in vivo development and neural cell replacement. Genetically modified cells can be generated to exhibit disease-related phenotypes and aberrant mechanisms for cellular and molecular analysis. Furthermore, they have the potential to be used as tools for early phase drug discovery by predicting in vivo drug response through in vitro cell-based assayology of drug candidates.

Disrupted-in-schizophrenia 1 (DISC1) is a risk factor for a variety of psychiatric and mental disorders, with mutant forms likely causing an overall loss of function in schizophenia.2, 3, 4 Non-human animal and cell-based studies indicate that DISC1 is a hub protein involved in multiple biochemical pathways, is highly expressed in the developing hippocampus (HP) and is localized to several subcellular domains including the centrosome, mitochondria, growth cone and synapse.5, 6, 7, 8, 9 DISC1 knockdown in maturing granule cells of the mouse HP causes aberrant cell migration, dendrite formation and axon termination.8, 9, 10 Reduced expression of DISC1 mRNA has been reported in lymphoblastoid cells of patients diagnosed with schizophrenia or chronic psychiatric illness.11 Taken together, cytogenetic and biological studies of DISC1 support the developmental hypothesis of schizophrenia.

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References

  1. Crook JM, Kobayashi NR . J Cell Biochem 2008; 105: 1361–1366.

    Article  CAS  PubMed  Google Scholar 

  2. Blackwood DH, Fordyce A, Walker MT, St Clair DM, Porteous DJ, Muir WJ . Am J Hum Genet 2001; 69: 428–433.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Chubb JE, Bradshaw NJ, Soares DC, Porteous DJ, Millar JK . Mol Psychiatry 2008; 13: 36–64.

    Article  CAS  PubMed  Google Scholar 

  4. Ishizuka K, Kamiya A, Sawa A . Biol Psychiatry 2006; 59: 1189–1197.

    Article  CAS  PubMed  Google Scholar 

  5. Pletnikov MV, Xu Y, Ovanesov MV, Kamiya A, Sawa A, Ross CA . Neurosci Res 2007; 58: 234–244.

    Article  CAS  PubMed  Google Scholar 

  6. James R, Adams RR, Christie S, Buchanan SR, Porteous DJ, Millar JK . Mol Cell Neurosci 2004; 26: 112–122.

    Article  CAS  PubMed  Google Scholar 

  7. Morris JA, Kandpal G, Ma L, Austin CP . Hum Mol Genet 2003; 12: 1591–1608.

    Article  CAS  PubMed  Google Scholar 

  8. Kamiya A, Kubo K, Tomoda T, Takaki M, Youn R, Ozeki Y et al. Nat Cell Biol 2005; 7: 1167–1178.

    Article  PubMed  Google Scholar 

  9. Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK et al. Cell 2009; 136: 1017–1031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim JY, Duan X, Liu CY, Jang MH, Guo JU, Pow-Anpongkul N et al. Neuron 2009; 63: 761–773.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Millar JK, Pickard BS, Mackie S, James R, Christie S, Buchanan SR et al. Science 2005; 310: 1187–1191.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Institute of Medical Biology, A*STAR, Singapore

    N R Kobayashi, L Sui, P S L Tan, E K H Lim & J M Crook

  2. Departments of Obstetrics and Gynaecology, National University of Singapore, Singapore

    J Chan & M Choolani

  3. O'Brien Institute and University of Melbourne, Melbourne, Victoria, Australia

    N R Kobayashi & J M Crook

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  1. N R Kobayashi
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  2. L Sui
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Correspondence to J M Crook.

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Kobayashi, N., Sui, L., Tan, P. et al. Modelling disrupted-in-schizophrenia 1 loss of function in human neural progenitor cells: tools for molecular studies of human neurodevelopment and neuropsychiatric disorders. Mol Psychiatry 15, 672–675 (2010). https://doi.org/10.1038/mp.2009.131

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