1932

Abstract

Mental health disorders are notoriously difficult to diagnose and treat for a variety of reasons, including genetic heterogeneity, comorbidities, and qualitative diagnostic criteria. Discovery of the molecular pathology underlying these disorders is crucial to the development of quantitative biomarkers and novel therapeutics. In this review, we discuss contributions to the mental health field of different cellular and whole-animal approaches in characterizing psychiatric genetics and molecular pathology. These approaches include mammalian cell and neuronal culture, cerebral organoids, induced pluripotent stem cells, and the whole-animal models of nematodes, flies, mollusks, frogs, mice, and zebrafish, on the last of which we place extra emphasis. Integrative use of these cellular and animal systems in a complementary and informative fashion maximizes the potential contributions to the mental health field as a whole.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-genom-090314-050048
2015-08-24
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/genom/16/1/annurev-genom-090314-050048.html?itemId=/content/journals/10.1146/annurev-genom-090314-050048&mimeType=html&fmt=ahah

Literature Cited

  1. Abbott A. 1.  2011. Novartis to shut brain research facility. Nature 480:161–62 [Google Scholar]
  2. Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD. 2.  et al. 2000. The genome sequence of Drosophila melanogaster. Science 287:2185–95 [Google Scholar]
  3. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. 3.  1999. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 23:185–88 [Google Scholar]
  4. Amsterdam A, Hopkins N. 4.  2006. Mutagenesis strategies in zebrafish for identifying genes involved in development and disease. Trends Genet. 22:473–78 [Google Scholar]
  5. Anderson G, Maes M. 5.  2012. Melatonin: an overlooked factor in schizophrenia and in the inhibition of anti-psychotic side effects. Metab. Brain Dis. 27:113–19 [Google Scholar]
  6. Arnedo J, Svrakic DM, Del Val C, Romero-Zaliz R, Hernández-Cuervo H. 6.  et al. 2015. Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. Am. J. Psychiatry 172:139–53 [Google Scholar]
  7. Asai A, Sahani N, Kaneki M, Ouchi Y, Martyn JA, Yasuhara SE. 7.  2007. Primary role of functional ischemia, quantitative evidence for the two-hit mechanism, and phosphodiesterase-5 inhibitor therapy in mouse muscular dystrophy. PLOS ONE 2:e806 [Google Scholar]
  8. Asakawa K, Kawakami K. 8.  2008. Targeted gene expression by the Gal4-UAS system in zebrafish. Dev. Growth Differ. 50:391–99 [Google Scholar]
  9. Bai X, Kim J, Yang Z, Jurynec MJ, Akie TE. 9.  et al. 2010. TIF1γ controls erythroid cell fate by regulating transcription elongation. Cell 142:133–43 [Google Scholar]
  10. Bernier R, Golzio C, Xiong B, Stessman HA, Coe BP. 10.  et al. 2014. Disruptive CHD8 mutations define a subtype of autism early in development. Cell 158:263–76 [Google Scholar]
  11. Bittencourt J, Velasques B, Teixeira S, Basile LF, Salles JI. 11.  et al. 2013. Saccadic eye movement applications for psychiatric disorders. Neuropsychiatr. Dis. Treat. 9:1393–409 [Google Scholar]
  12. Blaker-Lee A, Gupta S, McCammon JM, De Rienzo G, Sive H. 12.  2012. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes. Dis. Models Mech. 5:834–51 [Google Scholar]
  13. Blank M, Guerim LD, Cordeiro RF, Vianna MR. 13.  2009. A one-trial inhibitory avoidance task to zebrafish: rapid acquisition of an NMDA-dependent long-term memory. Neurobiol. Learn. Mem. 92:529–34 [Google Scholar]
  14. Bozdagi O, Sakurai T, Papapetrou D, Wang X, Dickstein DL. 14.  et al. 2010. Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol. Autism 1:15 [Google Scholar]
  15. Bozdagi O, Tavassoli T, Buxbaum JD. 15.  2013. Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay. Mol. Autism 4:9 [Google Scholar]
  16. Brady RO Jr, McCarthy JM, Prescot AP, Jensen JE, Cooper AJ. 16.  et al. 2013. Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder. Bipolar Disord. 15:434–39 [Google Scholar]
  17. Brenman JE, Chao DS, Xia H, Aldape K, Bredt DS. 17.  1995. Nitric oxide synthase complexed with dystrophin and absent from skeletal muscle sarcolemma in Duchenne muscular dystrophy. Cell 82:743–52 [Google Scholar]
  18. Brennan CH. 18.  2011. Zebrafish behavioural assays of translational relevance for the study of psychiatric disease. Rev. Neurosci. 22:37–48 [Google Scholar]
  19. Brennand KJ, Landek-Salgado MA, Sawa A. 19.  2014. Modeling heterogeneous patients with a clinical diagnosis of schizophrenia with induced pluripotent stem cells. Biol. Psychiatry 75:936–44 [Google Scholar]
  20. Brennand KJ, Savas JN, Kim Y, Tran N, Simone A. 20.  et al. 2015. Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol. Psychiatry 20:361–68 [Google Scholar]
  21. Brockschmidt A, Filippi A, Charbel Issa P, Nelles M, Urbach H. 21.  et al. 2011. Neurologic and ocular phenotype in Pitt-Hopkins syndrome and a zebrafish model. Hum. Genet. 130:645–55 [Google Scholar]
  22. Burguiere A, De Bundel D, Valjent E, Roger J, Smolders I. 22.  et al. 2013. Combination of group I mGlu receptors antagonist with dopaminergic agonists strengthens the synaptic transmission at corticostriatal synapses in culture. Neuropharmacology 66:151–57 [Google Scholar]
  23. Buske C, Gerlai R. 23.  2012. Maturation of shoaling behavior is accompanied by changes in the dopaminergic and serotoninergic systems in zebrafish. Dev. Psychobiol. 54:28–35 [Google Scholar]
  24. 24. C. elegans Seq. Consort 1998. Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282:2012–18 [Google Scholar]
  25. Cachat J, Stewart A, Grossman L, Gaikwad S, Kadri F. 25.  et al. 2010. Measuring behavioral and endocrine responses to novelty stress in adult zebrafish. Nat. Protoc. 5:1786–99 [Google Scholar]
  26. Cavarec L, Vincent L, Le Borgne C, Plusquellec C, Ollivier N. 26.  et al. 2013. In vitro screening for drug-induced depression and/or suicidal adverse effects: a new toxicogenomic assay based on CE-SSCP analysis of HTR2C mRNA editing in SH-SY5Y cells. Neurotox. Res. 23:49–62 [Google Scholar]
  27. Chadman KK, Gong S, Scattoni ML, Boltuck SE, Gandhy SU. 27.  et al. 2008. Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice. Autism Res. 1:147–58 [Google Scholar]
  28. Chen J, Lin M, Foxe JJ, Pedrosa E, Hrabovsky A. 28.  et al. 2013. Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts. PLOS ONE 8:e75682 [Google Scholar]
  29. Chen RZ, Akbarian S, Tudor M, Jaenisch R. 29.  2001. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat. Genet. 27:327–31 [Google Scholar]
  30. Choi YB, Li HL, Kassabov SR, Jin I, Puthanveettil SV. 30.  et al. 2011. Neurexin-neuroligin transsynaptic interaction mediates learning-related synaptic remodeling and long-term facilitation in Aplysia. Neuron 70:468–81 [Google Scholar]
  31. Cocchiaro JL, Rawls JF. 31.  2013. Microgavage of zebrafish larvae. J. Vis. Exp. 72:e4434 [Google Scholar]
  32. Coghlan S, Horder J, Inkster B, Mendez MA, Murphy DG, Nutt DJ. 32.  2012. GABA system dysfunction in autism and related disorders: from synapse to symptoms. Neurosci. Biobehav. Rev. 36:2044–55 [Google Scholar]
  33. Crawley JN. 33.  2012. Translational animal models of autism and neurodevelopmental disorders. Dialogues Clin. Neurosci. 14:293–305 [Google Scholar]
  34. 34. Cross-Disorder Group Psychiatr. Genomics Consort 2013. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 381:1371–79 [Google Scholar]
  35. Culetto E, Sattelle DB. 35.  2000. A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes. Hum. Mol. Genet. 9:869–77 [Google Scholar]
  36. Cutler C, Multani P, Robbins D, Kim HT, Le T. 36.  et al. 2013. Prostaglandin-modulated umbilical cord blood hematopoietic stem cell transplantation. Blood 122:3074–81 [Google Scholar]
  37. Dash PK, Hochner B, Kandel ER. 37.  1990. Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. Nature 345:718–21 [Google Scholar]
  38. De Rienzo G, Bishop JA, Mao Y, Pan L, Ma TP. 38.  et al. 2011. Disc1 regulates both β-catenin-mediated and noncanonical Wnt signaling during vertebrate embryogenesis. FASEB J. 25:4184–97 [Google Scholar]
  39. De Rienzo G, Gutzman JH, Sive H. 39.  2012. Efficient shRNA-mediated inhibition of gene expression in zebrafish. Zebrafish 9:97–107 [Google Scholar]
  40. DiBella LM, Park A, Sun Z. 40.  2009. Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway. Hum. Mol. Genet. 18:595–606 [Google Scholar]
  41. Dolen G, Osterweil E, Rao BS, Smith GB, Auerbach BD. 41.  et al. 2007. Correction of fragile X syndrome in mice. Neuron 56:955–62 [Google Scholar]
  42. Drapeau E, Dorr NP, Elder GA, Buxbaum JD. 42.  2014. Absence of strong strain effects in behavioral analyses of Shank3-deficient mice. Dis. Models Mech. 7:667–81 [Google Scholar]
  43. Drerup CM, Wiora HM, Topczewski J, Morris JA. 43.  2009. Disc1 regulates foxd3 and sox10 expression, affecting neural crest migration and differentiation. Development 136:2623–32 [Google Scholar]
  44. Dueck A, Thome J, Haessler F. 44.  2012. The role of sleep problems and circadian clock genes in childhood psychiatric disorders. J. Neural Transm. 119:1097–104 [Google Scholar]
  45. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P. 45.  et al. 2007. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat. Genet. 39:25–27 [Google Scholar]
  46. Dykens EM, Sutcliffe JS, Levitt P. 46.  2004. Autism and 15q11-q13 disorders: behavioral, genetic, and pathophysiological issues. Ment. Retard. Dev. Disabil. Res. Rev. 10:284–91 [Google Scholar]
  47. Edwards D, Stancescu M, Molnar P, Hickman JJ. 47.  2013. Two cell circuits of oriented adult hippocampal neurons on self-assembled monolayers for use in the study of neuronal communication in a defined system. ACS Chem. Neurosci. 4:1174–82 [Google Scholar]
  48. Elbaz I, Foulkes NS, Gothilf Y, Appelbaum L. 48.  2013. Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish. Front. Neural Circ. 7:9 [Google Scholar]
  49. Elsen GE, Choi LY, Prince VE, Ho RK. 49.  2009. The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration. Dev. Biol. 335:78–92 [Google Scholar]
  50. Ermolaeva MA, Schumacher B. 50.  2014. Insights from the worm: the C. elegans model for innate immunity. Semin. Immunol. 26:303–9 [Google Scholar]
  51. Fajardo O, Zhu P, Friedrich RW. 51.  2013. Control of a specific motor program by a small brain area in zebrafish. Front. Neural Circ. 7:67 [Google Scholar]
  52. Flint J, Timpson N, Munafo M. 52.  2014. Assessing the utility of intermediate phenotypes for genetic mapping of psychiatric disease. Trends Neurosci. 37:733–41 [Google Scholar]
  53. Gabriele S, Sacco R, Persico AM. 53.  2014. Blood serotonin levels in autism spectrum disorder: a systematic review and meta-analysis. Eur. Neuropsychopharmacol. 24:919–29 [Google Scholar]
  54. Gauthier J, Champagne N, Lafreniere RG, Xiong L, Spiegelman D. 54.  et al. 2010. De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia. PNAS 107:7863–68 [Google Scholar]
  55. Gibbs EM, Horstick EJ, Dowling JJ. 55.  2013. Swimming into prominence: the zebrafish as a valuable tool for studying human myopathies and muscular dystrophies. FEBS J. 280:4187–97 [Google Scholar]
  56. Goessling W, Allen RS, Guan X, Jin P, Uchida N. 56.  et al. 2011. Prostaglandin E2 enhances human cord blood stem cell xenotransplants and shows long-term safety in preclinical nonhuman primate transplant models. Cell Stem Cell 8:445–58 [Google Scholar]
  57. Golzio C, Willer J, Talkowski ME, Oh EC, Taniguchi Y. 57.  et al. 2012. KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant. Nature 485:363–67 [Google Scholar]
  58. Grunblatt E, Bartl J, Marinova Z, Walitza S. 58.  2013. In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder. J. Neural Transm. 120:131–39 [Google Scholar]
  59. Guy J, Hendrich B, Holmes M, Martin JE, Bird A. 59.  2001. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat. Genet. 27:322–26 [Google Scholar]
  60. Hallcher LM, Sherman WR. 60.  1980. The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain. J. Biol. Chem. 255:10896–901 [Google Scholar]
  61. Hamdani N, Doukhan R, Kurtlucan O, Tamouza R, Leboyer M. 61.  2013. Immunity, inflammation, and bipolar disorder: diagnostic and therapeutic implications. Curr. Psychiatry Rep. 15:387 [Google Scholar]
  62. Hao J, Ao A, Zhou L, Murphy CK, Frist AY. 62.  et al. 2013. Selective small molecule targeting β-catenin function discovered by in vivo chemical genetic screen. Cell Rep. 4:898–904 [Google Scholar]
  63. Hashimoto M, Hibi M. 63.  2012. Development and evolution of cerebellar neural circuits. Dev. Growth Differ. 54:373–89 [Google Scholar]
  64. Hayashi-Takagi A, Araki Y, Nakamura M, Vollrath B, Duron SG. 64.  et al. 2014. PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence. PNAS 111:6461–66 [Google Scholar]
  65. He X, Saint-Jeannet JP, Woodgett JR, Varmus HE, Dawid IB. 65.  1995. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature 374:617–22 [Google Scholar]
  66. Helenius IT, Yeh JR. 66.  2012. Small zebrafish in a big chemical pond. J. Cell. Biochem. 113:2208–16 [Google Scholar]
  67. Hisano Y, Ota S, Kawahara A. 67.  2014. Genome editing using artificial site-specific nucleases in zebrafish. Dev. Growth Differ. 56:26–33 [Google Scholar]
  68. Hodgkin AL, Huxley AF. 68.  1939. Action potentials recorded from inside a nerve fibre. Nature 144:710–11 [Google Scholar]
  69. Howe K, Clark MD, Torroja CF, Torrance J, Berthelot C. 69.  et al. 2013. The zebrafish reference genome sequence and its relationship to the human genome. Nature 496:498–503 [Google Scholar]
  70. Huber KM, Gallagher SM, Warren ST, Bear MF. 70.  2002. Altered synaptic plasticity in a mouse model of fragile X mental retardation. PNAS 99:7746–50 [Google Scholar]
  71. Hunt PR, Olejnik N, Sprando RL. 71.  2012. Toxicity ranking of heavy metals with screening method using adult Caenorhabditis elegans and propidium iodide replicates toxicity ranking in rat. Food Chem. Toxicol. 50:3280–90 [Google Scholar]
  72. Jacquemont S, Curie A, des Portes V, Torrioli MG, Berry-Kravis E. 72.  et al. 2011. Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci. Transl. Med. 3:64ra1 [Google Scholar]
  73. Jamain S, Quach H, Betancur C, Rastam M, Colineaux C. 73.  et al. 2003. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34:27–29 [Google Scholar]
  74. Kaitin KI, Milne CP. 74.  2011. A dearth of new meds. Sci. Am. 305:16 [Google Scholar]
  75. Kao KR, Masui Y, Elinson RP. 75.  1986. Lithium-induced respecification of pattern in Xenopus laevis embryos. Nature 322:371–73 [Google Scholar]
  76. Kawahara G, Karpf JA, Myers JA, Alexander MS, Guyon JR, Kunkel LM. 76.  2011. Drug screening in a zebrafish model of Duchenne muscular dystrophy. PNAS 108:5331–36 [Google Scholar]
  77. Kendler KS. 77.  2013. What psychiatric genetics has taught us about the nature of psychiatric illness and what is left to learn. Mol. Psychiatry 18:1058–66 [Google Scholar]
  78. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. 78.  2005. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62:593–602 [Google Scholar]
  79. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. 79.  2005. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62:617–27 [Google Scholar]
  80. Kettleborough RN, Busch-Nentwich EM, Harvey SA, Dooley CM, de Bruijn E. 80.  et al. 2013. A systematic genome-wide analysis of zebrafish protein-coding gene function. Nature 496:494–97 [Google Scholar]
  81. Khan KH, Blanco-Codesido M, Molife LR. 81.  2014. Cancer therapeutics: targeting the apoptotic pathway. Crit. Rev. Oncol. Hematol. 90:200–19 [Google Scholar]
  82. Kim HG, Kishikawa S, Higgins AW, Seong IS, Donovan DJ. 82.  et al. 2008. Disruption of neurexin 1 associated with autism spectrum disorder. Am. J. Hum. Genet. 82:199–207 [Google Scholar]
  83. Kim SH, Speirs CK, Solnica-Krezel L, Ess KC. 83.  2011. Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin. Dis. Models Mech. 4:255–67 [Google Scholar]
  84. Kimura Y, Satou C, Fujioka S, Shoji W, Umeda K. 84.  et al. 2013. Hindbrain V2a neurons in the excitation of spinal locomotor circuits during zebrafish swimming. Curr. Biol. 23:843–49 [Google Scholar]
  85. Klein PS, Melton DA. 85.  1996. A molecular mechanism for the effect of lithium on development. PNAS 93:8455–59 [Google Scholar]
  86. Kohane IS, McMurry A, Weber G, MacFadden D, Rappaport L. 86.  et al. 2012. The co-morbidity burden of children and young adults with autism spectrum disorders. PLOS ONE 7:e33224 [Google Scholar]
  87. Kokel D, Bryan J, Laggner C, White R, Cheung CY. 87.  et al. 2010. Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nat. Chem. Biol. 6:231–37 [Google Scholar]
  88. Konopka RJ, Benzer S. 88.  1971. Clock mutants of Drosophila melanogaster. PNAS 68:2112–16 [Google Scholar]
  89. Lancaster MA, Knoblich JA. 89.  2014. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:1247125 [Google Scholar]
  90. Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS. 90.  et al. 2013. Cerebral organoids model human brain development and microcephaly. Nature 501:373–79 [Google Scholar]
  91. Lindor NM, McMaster ML, Lindor CJ, Greene MH. 91.  2008. Concise handbook of familial cancer susceptibility syndromes—second edition. J. Natl. Cancer Inst. Monogr. 2008:3–93 [Google Scholar]
  92. Lindsay EA, Morris MA, Gos A, Nestadt G, Wolyniec PS. 92.  et al. 1995. Schizophrenia and chromosomal deletions within 22q11.2. Am. J. Hum. Genet. 56:1502–3 [Google Scholar]
  93. Lord C, Petkova E, Hus V, Gan W, Lu F. 93.  et al. 2012. A multisite study of the clinical diagnosis of different autism spectrum disorders. Arch. Gen. Psychiatry 69:306–13 [Google Scholar]
  94. M'Hamdi O, Ouertani I, Chaabouni-Bouhamed H. 94.  2014. Update on the genetics of Bardet-Biedl syndrome. Mol. Syndromol. 5:51–56 [Google Scholar]
  95. Maaswinkel H, Zhu L, Weng W. 95.  2013. Assessing social engagement in heterogeneous groups of zebrafish: a new paradigm for autism-like behavioral responses. PLOS ONE 8:e75955 [Google Scholar]
  96. Malhotra D, Sebat J. 96.  2012. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell 148:1223–41 [Google Scholar]
  97. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW. 97.  et al. 2010. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143:527–39 [Google Scholar]
  98. Martin EA, Barresi R, Byrne BJ, Tsimerinov EI, Scott BL. 98.  et al. 2012. Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy. Sci. Transl. Med. 4:162ra55 [Google Scholar]
  99. Maximino C, de Brito TM, da Silva Batista AW, Herculano AM, Morato S, Gouveia A Jr. 99.  2010. Measuring anxiety in zebrafish: a critical review. Behav. Brain Res. 214:157–71 [Google Scholar]
  100. McBride SM, Choi CH, Wang Y, Liebelt D, Braunstein E. 100.  et al. 2005. Pharmacological rescue of synaptic plasticity, courtship behavior, and mushroom body defects in a Drosophila model of fragile X syndrome. Neuron 45:753–64 [Google Scholar]
  101. McLaren D, Gorba T, Marguerie de Rotrou A, Pillai G, Chappell C. 101.  et al. 2013. Automated large-scale culture and medium-throughput chemical screen for modulators of proliferation and viability of human induced pluripotent stem cell-derived neuroepithelial-like stem cells. J. Biomol. Screen. 18:258–68 [Google Scholar]
  102. McMahon AP, Moon RT. 102.  1989. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis. Cell 58:1075–84 [Google Scholar]
  103. Merikangas KR, He JP, Burstein M, Swanson SA, Avenevoli S. 103.  et al. 2010. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication–Adolescent Supplement (NCS-A). J. Am. Acad. Child Adolesc. Psychiatry 49:980–89 [Google Scholar]
  104. Miller G. 104.  2010. Is pharma running out of brainy ideas?. Science 329:502–4 [Google Scholar]
  105. Moretti P, Bouwknecht JA, Teague R, Paylor R, Zoghbi HY. 105.  2005. Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome. Hum. Mol. Genet. 14:205–20 [Google Scholar]
  106. 106. Mouse Genome Seq. Consort 2002. Initial sequencing and comparative analysis of the mouse genome. Nature 420:520–62 [Google Scholar]
  107. Mukai J, Dhilla A, Drew LJ, Stark KL, Cao L. 107.  et al. 2008. Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion. Nat. Neurosci. 11:1302–10 [Google Scholar]
  108. Nakatani J, Tamada K, Hatanaka F, Ise S, Ohta H. 108.  et al. 2009. Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism. Cell 137:1235–46 [Google Scholar]
  109. Nasevicius A, Ekker SC. 109.  2000. Effective targeted gene “knockdown” in zebrafish. Nat. Genet. 26:216–20 [Google Scholar]
  110. Neill JC, Barnes S, Cook S, Grayson B, Idris NF. 110.  et al. 2010. Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. Pharmacol. Ther. 128:419–32 [Google Scholar]
  111. Nelson MD, Rader F, Tang X, Tavyev J, Nelson SF. 111.  et al. 2014. PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy. Neurology 82:2085–91 [Google Scholar]
  112. Ng MC, Yang YL, Lu KT. 112.  2013. Behavioral and synaptic circuit features in a zebrafish model of fragile X syndrome. PLOS ONE 8:e51456 [Google Scholar]
  113. North TE, Goessling W, Walkley CR, Lengerke C, Kopani KR. 113.  et al. 2007. Prostaglandin E2 regulates vertebrate haematopoietic stem cell homeostasis. Nature 447:1007–11 [Google Scholar]
  114. O'Brien WT, Klein PS. 114.  2009. Validating GSK3 as an in vivo target of lithium action. Biochem. Soc. Trans. 37:1133–38 [Google Scholar]
  115. Panula P, Chen YC, Priyadarshini M, Kudo H, Semenova S. 115.  et al. 2010. The comparative neuroanatomy and neurochemistry of zebrafish CNS systems of relevance to human neuropsychiatric diseases. Neurobiol. Dis. 40:46–57 [Google Scholar]
  116. Pariante CM. 116.  2009. Risk factors for development of depression and psychosis: glucocorticoid receptors and pituitary implications for treatment with antidepressant and glucocorticoids. Ann. N.Y. Acad. Sci. 1179:144–52 [Google Scholar]
  117. Pasca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov A. 117.  et al. 2011. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat. Med. 17:1657–62 [Google Scholar]
  118. Patel JN, McLeod HL, Innocenti F. 118.  2013. Implications of genome-wide association studies in cancer therapeutics. Br. J. Clin. Pharmacol. 76:370–80 [Google Scholar]
  119. Peal DS, Mills RW, Lynch SN, Mosley JM, Lim E. 119.  et al. 2011. Novel chemical suppressors of long QT syndrome identified by an in vivo functional screen. Circulation 123:23–30 [Google Scholar]
  120. Peca J, Feliciano C, Ting JT, Wang W, Wells MF. 120.  et al. 2011. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472:437–42 [Google Scholar]
  121. Petrij F, Giles RH, Dauwerse HG, Saris JJ, Hennekam RC. 121.  et al. 1995. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376:348–51 [Google Scholar]
  122. Pietri T, Roman AC, Guyon N, Romano SA, Washbourne P. 122.  et al. 2013. The first mecp2-null zebrafish model shows altered motor behaviors. Front. Neural Circuits 7:118 [Google Scholar]
  123. Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A. 123.  et al. 2014. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am. J. Hum. Genet. 94:677–94 [Google Scholar]
  124. Poon KL, Brand T. 124.  2013. The zebrafish model system in cardiovascular research: a tiny fish with mighty prospects. Glob. Cardiol. Sci. Pract. 2013:9–28 [Google Scholar]
  125. Prilutsky D, Palmer NP, Smedemark-Margulies N, Schlaeger TM, Margulies DM, Kohane IS. 125.  2014. iPSC-derived neurons as a higher-throughput readout for autism: promises and pitfalls. Trends Mol. Med. 20:91–104 [Google Scholar]
  126. Ramachandran KV, Hennessey JA, Barnett AS, Yin X, Stadt HA. 126.  et al. 2013. Calcium influx through L-type CaV1.2 Ca2+ channels regulates mandibular development. J. Clin. Investig. 123:1638–46 [Google Scholar]
  127. Randall FE, Garcia-Munoz M, Vickers C, Schock SC, Staines WA, Arbuthnott GW. 127.  2011. The corticostriatal system in dissociated cell culture. Front. Syst. Neurosci. 5:52 [Google Scholar]
  128. Ranga A, Gjorevski N, Lutolf MP. 128.  2014. Drug discovery through stem cell-based organoid models. Adv. Drug Deliv. Rev. 69–70C:19–28 [Google Scholar]
  129. Rayport SG, Schacher S. 129.  1986. Synaptic plasticity in vitro: cell culture of identified Aplysia neurons mediating short-term habituation and sensitization. J. Neurosci. 6:759–63 [Google Scholar]
  130. Reeber SL, Otis TS, Sillitoe RV. 130.  2013. New roles for the cerebellum in health and disease. Front. Syst. Neurosci. 7:83 [Google Scholar]
  131. Reiter LT, Potocki L, Chien S, Gribskov M, Bier E. 131.  2001. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 11:1114–25 [Google Scholar]
  132. Renshaw SA, Trede NS. 132.  2012. A model 450 million years in the making: zebrafish and vertebrate immunity. Dis. Models Mech. 5:38–47 [Google Scholar]
  133. Rihel J, Prober DA, Arvanites A, Lam K, Zimmerman S. 133.  et al. 2010. Zebrafish behavioral profiling links drugs to biological targets and rest/wake regulation. Science 327:348–51 [Google Scholar]
  134. Rizak J, Tan H, Zhu H, Wang JF. 134.  2014. Chronic treatment with the mood stabilizing drug lithium up-regulates nuclear factor E2-related factor 2 in rat pheochromocytoma PC12 cells in vitro. Neuroscience 256:223–29 [Google Scholar]
  135. Robu ME, Larson JD, Nasevicius A, Beiraghi S, Brenner C. 135.  et al. 2007. p53 activation by knockdown technologies. PLOS Genet. 3:e78 [Google Scholar]
  136. Rossignol DA, Frye RE. 136.  2011. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev. Med. Child Neurol. 53:783–92 [Google Scholar]
  137. Saur T, DeMarco SE, Ortiz A, Sliwoski GR, Hao L. 137.  et al. 2013. A genome-wide RNAi screen in Caenorhabditis elegans identifies the nicotinic acetylcholine receptor subunit ACR-7 as an antipsychotic drug target. PLOS Genet. 9:e1003313 [Google Scholar]
  138. Schaz U, Fohr KJ, Liebau S, Fulda S, Koelch M. 138.  et al. 2011. Dose-dependent modulation of apoptotic processes by fluoxetine in maturing neuronal cells: an in vitro study. World J. Biol. Psychiatry 12:89–98 [Google Scholar]
  139. 139. Schizophr. Work. Group Psychiatr. Genomics Consort 2014. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–27 [Google Scholar]
  140. Schmold N, Syed NI. 140.  2012. Molluscan neurons in culture: shedding light on synapse formation and plasticity. J. Mol. Histol. 43:383–99 [Google Scholar]
  141. Schoonheim PJ, Arrenberg AB, Del Bene F, Baier H. 141.  2010. Optogenetic localization and genetic perturbation of saccade-generating neurons in zebrafish. J. Neurosci. 30:7111–20 [Google Scholar]
  142. Scott EK, Mason L, Arrenberg AB, Ziv L, Gosse NJ. 142.  et al. 2007. Targeting neural circuitry in zebrafish using GAL4 enhancer trapping. Nat. Methods 4:323–26 [Google Scholar]
  143. Shcheglovitov A, Shcheglovitova O, Yazawa M, Portmann T, Shu R. 143.  et al. 2013. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 503:267–71 [Google Scholar]
  144. Shepherd I, Eisen J. 144.  2011. Development of the zebrafish enteric nervous system. Methods Cell Biol. 101:143–60 [Google Scholar]
  145. Shih DF, Hsiao CD, Min MY, Lai WS, Yang CW. 145.  et al. 2013. Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions. PLOS ONE 8:e71741 [Google Scholar]
  146. Siegfried E, Wilder EL, Perrimon N. 146.  1994. Components of wingless signalling in Drosophila. Nature 367:76–80 [Google Scholar]
  147. Simonoff E, Pickles A, Charman T, Chandler S, Loucas T, Baird G. 147.  2008. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J. Am. Acad. Child Adolesc. Psychiatry 47:921–29 [Google Scholar]
  148. Singh KK, De Rienzo G, Drane L, Mao Y, Flood Z. 148.  et al. 2011. Common DISC1 polymorphisms disrupt Wnt/GSK3β signaling and brain development. Neuron 72:545–58 [Google Scholar]
  149. Sive H. 149.  2011. “Model” or “tool”? New definitions for translational research. Dis. Models Mech. 4:137–38 [Google Scholar]
  150. Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE. 150.  et al. 2011. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470:105–9 [Google Scholar]
  151. Stan AD, Lewis DA. 151.  2012. Altered cortical GABA neurotransmission in schizophrenia: insights into novel therapeutic strategies. Curr. Pharm. Biotechnol. 13:1557–62 [Google Scholar]
  152. Stark KL, Xu B, Bagchi A, Lai WS, Liu H. 152.  et al. 2008. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat. Genet. 40:751–60 [Google Scholar]
  153. Stewart AM, Nguyen M, Wong K, Poudel MK, Kalueff AV. 153.  2014. Developing zebrafish models of autism spectrum disorder (ASD). Prog. Neuro-Psychopharmacol. Biol. Psychiatry 50:27–36 [Google Scholar]
  154. Sullivan PF, Daly MJ, O'Donovan M. 154.  2012. Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat. Rev. Genet. 13:537–51 [Google Scholar]
  155. Sulston JE, Horvitz HR. 155.  1977. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev. Biol. 56:110–56 [Google Scholar]
  156. Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X. 156.  et al. 2007. A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318:71–76 [Google Scholar]
  157. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T. 157.  et al. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–72 [Google Scholar]
  158. Takebe T, Sekine K, Enomura M, Koike H, Kimura M. 158.  et al. 2013. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499:481–84 [Google Scholar]
  159. Tayeh MK, Yen HJ, Beck JS, Searby CC, Westfall TA. 159.  et al. 2008. Genetic interaction between Bardet-Biedl syndrome genes and implications for limb patterning. Hum. Mol. Genet. 17:1956–67 [Google Scholar]
  160. Thomas KR, Capecchi MR. 160.  1987. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 51:503–12 [Google Scholar]
  161. Tian LJ, Cao JH, Deng XQ, Zhang CL, Qian T. 161.  et al. 2014. Gene expression profiling of Duchenne muscular dystrophy reveals characteristics along disease progression. Genet. Mol. Res. 13:1402–11 [Google Scholar]
  162. Toma C, Hervas A, Balmana N, Salgado M, Maristany M. 162.  et al. 2013. Neurotransmitter systems and neurotrophic factors in autism: association study of 37 genes suggests involvement of DDC. World J. Biol. Psychiatry 14:516–27 [Google Scholar]
  163. Trillenberg P, Lencer R, Heide W. 163.  2004. Eye movements and psychiatric disease. Curr. Opin. Neurol. 17:43–47 [Google Scholar]
  164. Tropea D, Giacometti E, Wilson NR, Beard C, McCurry C. 164.  et al. 2009. Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice. PNAS 106:2029–34 [Google Scholar]
  165. Vashlishan AB, Madison JM, Dybbs M, Bai J, Sieburth D. 165.  et al. 2008. An RNAi screen identifies genes that regulate GABA synapses. Neuron 58:346–61 [Google Scholar]
  166. Voas MG, Glenn TD, Raphael AR, Talbot WS. 166.  2009. Schwann cells inhibit ectopic clustering of axonal sodium channels. J. Neurosci. 29:14408–14 [Google Scholar]
  167. Voleti B, Duman RS. 167.  2012. The roles of neurotrophic factor and Wnt signaling in depression. Clin. Pharmacol. Ther. 91:333–38 [Google Scholar]
  168. Wang X, McCoy PA, Rodriguiz RM, Pan Y, Je HS. 168.  et al. 2011. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum. Mol. Genet. 20:3093–108 [Google Scholar]
  169. Wartha K, Herting F, Hasmann M. 169.  2014. Fit-for purpose use of mouse models to improve predictivity of cancer therapeutics evaluation. Pharmacol. Ther. 142:351–61 [Google Scholar]
  170. Weger BD, Weger M, Nusser M, Brenner-Weiss G, Dickmeis T. 170.  2012. A chemical screening system for glucocorticoid stress hormone signaling in an intact vertebrate. ACS Chem. Biol. 7:1178–83 [Google Scholar]
  171. White JG, Southgate E, Thomson JN, Brenner S. 171.  1986. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos. Trans. R. Soc. Lond. B 314:1–340 [Google Scholar]
  172. White RM, Cech J, Ratanasirintrawoot S, Lin CY, Rahl PB. 172.  et al. 2011. DHODH modulates transcriptional elongation in the neural crest and melanoma. Nature 471:518–22 [Google Scholar]
  173. White RM, Rose K, Zon L. 173.  2013. Zebrafish cancer: the state of the art and the path forward. Nat. Rev. Cancer 13:624–36 [Google Scholar]
  174. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ. 174.  et al. 2013. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 382:1575–86 [Google Scholar]
  175. Wolman MA, Jain RA, Liss L, Granato M. 175.  2011. Chemical modulation of memory formation in larval zebrafish. PNAS 108:15468–73 [Google Scholar]
  176. Woods IG, Kelly PD, Chu F, Ngo-Hazelett P, Yan YL. 176.  et al. 2000. A comparative map of the zebrafish genome. Genome Res. 10:1903–14 [Google Scholar]
  177. Wray NR, Lee SH, Mehta D, Vinkhuyzen AA, Dudbridge F, Middeldorp CM. 177.  2014. Research review: polygenic methods and their application to psychiatric traits. J. Child Psychol. Psychiatry 55:1068–87 [Google Scholar]
  178. Wyart C, Del Bene F, Warp E, Scott EK, Trauner D. 178.  et al. 2009. Optogenetic dissection of a behavioural module in the vertebrate spinal cord. Nature 461:407–10 [Google Scholar]
  179. Yan QJ, Rammal M, Tranfaglia M, Bauchwitz RP. 179.  2005. Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP. Neuropharmacology 49:1053–66 [Google Scholar]
  180. Yang M, Bozdagi O, Scattoni ML, Wohr M, Roullet FI. 180.  et al. 2012. Reduced excitatory neurotransmission and mild autism-relevant phenotypes in adolescent Shank3 null mutant mice. J. Neurosci. 32:6525–41 [Google Scholar]
  181. Young JJ, Cherone JM, Doyon Y, Ankoudinova I, Faraji FM. 181.  et al. 2011. Efficient targeted gene disruption in the soma and germ line of the frog Xenopus tropicalis using engineered zinc-finger nucleases. PNAS 108:7052–57 [Google Scholar]
  182. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL. 182.  et al. 2007. Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–20 [Google Scholar]
  183. Ziv L, Muto A, Schoonheim PJ, Meijsing SH, Strasser D. 183.  et al. 2013. An affective disorder in zebrafish with mutation of the glucocorticoid receptor. Mol. Psychiatry 18:681–91 [Google Scholar]
/content/journals/10.1146/annurev-genom-090314-050048
Loading
/content/journals/10.1146/annurev-genom-090314-050048
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error