Integrative transcriptome network analysis of iPSC-derived neurons from schizophrenia and schizoaffective disorder patients with 22q11.2 deletion

BMC Systems Biology

Volumn 10, Issue 1, 2016, Pages

  Lin, Mingyan ^a   Pedrosa, Erika ^a   Hrabovsky, Anastasia ^a   Chen, Jian ^a   Puliafito, Benjamin R ^a   Gilbert, Stephanie R ^a   Zheng, Deyou ^a   Lachman, Herbert M ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN; CELL LINE; CHROMOSOME 22; CHROMOSOME DELETION; CYTOLOGY; GENE EXPRESSION PROFILING; GENE REGULATORY NETWORK; GENETICS; GROWTH, DEVELOPMENT AND AGING; HUMAN; INDUCED PLURIPOTENT STEM CELL; METABOLISM; NERVE CELL; PATHOLOGY; PATHOPHYSIOLOGY; PSYCHOSIS; SCHIZOPHRENIA;

BRAIN; CELL LINE; CHROMOSOME DELETION; CHROMOSOMES, HUMAN, PAIR 22; GENE EXPRESSION PROFILING; GENE REGULATORY NETWORKS; HUMANS; INDUCED PLURIPOTENT STEM CELLS; NEURONS; PSYCHOTIC DISORDERS; SCHIZOPHRENIA;

EID: 84999098100     PISSN: None     EISSN: 17520509     Source Type: Journal    
DOI: 10.1186/s12918-016-0366-0     Document Type: Article

References (138)

1. Sundram F, Murphy KC. Schizophrenia and 22q11. 2 Deletion Syndrome. eLS. Chichester: John Wiley & Sons Ltd. 2011. DOI: 10.1002/9780470015902.a0005229.pub2.
2. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch Gen Psychiatry. 1999;56(10):940-5.
3. van Amelsvoort T, Daly E, Henry J, Robertson D, Ng V, Owen M, et al. Brain anatomy in adults with velocardiofacial syndrome with and without Schizophrenia: preliminary results of a structural magnetic resonance imaging study. Arch Gen Psychiatry. 2004;61(11):1085-96.
4. Shprintzen R, Goldberg R, Lewin M, Sidoti E, Berkman M, Argamaso R, et al. A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: velo-cardio-facial syndrome. Cleft Palate J. 1978;15(1):56-62.
5. Scambler P, Kelly D, Lindsay E, Williamson R, Goldberg R, Shprintzen R, et al. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus. Lancet. 1992;339(8802):1138-9.
6. Driscoll D, Budarf M, Emanuel B. A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am J Hum Genet. 1992;50(5):924.
7. Bassett AS, Chow EW. Schizophrenia and 22q11. 2 deletion syndrome. Curr Psychiatry Rep. 2008;10(2):148-57.
8. Arinami T. Analyses of the associations between the genes of 22q11 deletion syndrome and schizophrenia. J Hum Genet. 2006;51(12):1037-45.
9. Maynard T, Haskell G, Peters A, Sikich L, Lieberman J, LaMantia A-S. A comprehensive analysis of 22q11 gene expression in the developing and adult brain. Proc Natl Acad Sci U S A. 2003;100(24):14433-8.
10. Raux G, Bumsel E, Hecketsweiler B, van Amelsvoort T, Zinkstok J, Manouvrier-Hanu S, et al. Involvement of hyperprolinemia in cognitive and psychiatric features of the 22q11 deletion syndrome. Hum Mol Genet. 2007;16(1):83-91.
11. Lachman HM, Papolos DF, Saito T, Yu Y-M, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenet Genomics. 1996;6(3):243-50.
12. Williams NM, Glaser B, Norton N, Williams H, Pierce T, Moskvina V, et al. Strong evidence that GNB1L is associated with schizophrenia. Hum Mol Genet. 2008;17(4):555-66.
13. Jacquet H, Raux G, Thibaut F, Hecketsweiler B, Houy E, Demilly C, et al. PRODH mutations and hyperprolinemia in a subset of schizophrenic patients. Hum Mol Genet. 2002;11(19):2243-9.
14. Liu H, Heath SC, Sobin C, Roos JL, Galke BL, Blundell ML, et al. Genetic variation at the 22q11 PRODH2/DGCR6 locus presents an unusual pattern and increases susceptibility to schizophrenia. Proc Natl Acad Sci U S A. 2002;99(6):3717-22.
15. Li T, Ma X, Sham PC, Sun X, Hu X, Wang Q, et al. Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population. Am J Med Genet B Neuropsychiatr Genet. 2004;129(1):13-5.
16. Kempf L, Nicodemus KK, Kolachana B, Vakkalanka R, Verchinski BA, Egan MF, et al. Functional polymorphisms in PRODH are associated with risk and protection for schizophrenia and fronto-striatal structure and function. PLoS Genet. 2008;4(11):e1000252.
17. Ouchi Y, Banno Y, Shimizu Y, Ando S, Hasegawa H, Adachi K, et al. Reduced adult hippocampal neurogenesis and working memory deficits in the Dgcr8-deficient mouse model of 22q11. 2 deletion-associated schizophrenia can be rescued by IGF2. J Neurosci. 2013;33(22):9408-19.
18. Beveridge N, Gardiner E, Carroll A, Tooney P, Cairns M. Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry. 2010;15(12):1176-89.
19. Chen Z, Wu J, Yang C, Fan P, Balazs L, Jiao Y, et al. DiGeorge syndrome critical region 8 (DGCR8) protein-mediated microRNA biogenesis is essential for vascular smooth muscle cell development in mice. J Biol Chem. 2012;287(23):19018-28.
20. Meechan D, Maynard T, Gopalakrishna D, Wu Y. When half is not enough: gene expression and dosage in the 22q11 deletion syndrome. Gene Expr. 2006;13(6):299-310.
21. Stark KL, Xu B, Bagchi A, Lai W-S, Liu H, Hsu R, et al. Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet. 2008;40(6):751-60.
22. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4):663-76.
23. Lin M, Zhao D, Hrabovsky A, Pedrosa E, Zheng D, Lachman HM. Heat shock alters the expression of schizophrenia and autism candidate genes in an induced pluripotent stem cell model of the human telencephalon. PLoS One. 2014;9(4):e94968.
24. Lin M, Pedrosa E, Shah A, Hrabovsky A, Maqbool S, Zheng D, et al. RNA-Seq of human neurons derived from iPS cells reveals candidate long non-coding RNAs involved in neurogenesis and neuropsychiatric disorders. PLoS One. 2011;6(9):e23356.
25. Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011;473(7346):221-5.
26. Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, et al. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell. 2010;143(4):527-39.
27. Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Chung W, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science. 2008;321(5893):1218-21.
28. Wernig M, Zhao J-P, Pruszak J, Hedlund E, Fu D, Soldner F, et al. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci U S A. 2008;105(15):5856-61.
29. Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, et al. Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature. 2009;461(7262):402-6.
30. Lin M, Lachman HM, Zheng D. Transcriptomics analysis of iPSC-derived neurons and modeling of neuropsychiatric disorders. Mol Cell Neurosci. 2016; In press.
31. Gassó P, Mas S, Molina O, Lafuente A, Bernardo M, Parellada E. Increased susceptibility to apoptosis in cultured fibroblasts from antipsychotic-naïve first-episode schizophrenia patients. J Psychiatr Res. 2014;48(1):94-101.
32. Glantz LA, Gilmore JH, Lieberman JA, Jarskog LF. Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res. 2006;81(1):47-63.
33. Boyajyan A, Chavushyan A, Zakharyan R, Mkrtchyan G. Markers of apoptotic dysfunctions in schizophrenia. Mol Biol. 2013;47(4):587-91.
34. Zhao D, Lin M, Chen J, Pedrosa E, Hrabovsky A, Fourcade HM, et al. MicroRNA profiling of neurons generated using induced pluripotent stem cells derived from patients with schizophrenia and schizoaffective disorder, and 22q11. 2 Del. PLoS One. 2015;10(7):e0132387.
35. Lin M, Hrabovsky A, Pedrosa E, Wang T, Zheng D, Lachman HM. Allele-biased expression in differentiating human neurons: implications for neuropsychiatric disorders. PLoS One. 2012;7(8):e44017.
36. Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, et al. A more efficient method to generate integration-free human iPS cells. Nat Methods. 2011;8(5):409-12.
37. Muenthaisong S, Ujhelly O, Polgar Z, Varga E, Ivics Z, Pirity MK, et al. Generation of mouse induced pluripotent stem cells from different genetic backgrounds using Sleeping beauty transposon mediated gene transfer. Exp Cell Res. 2012;318(19):2482-9.
38. Pal R, Mamidi MK, Das AK, Bhonde R. Comparative analysis of cardiomyocyte differentiation from human embryonic stem cells under 3-D and 2-D culture conditions. J Biosci Bioeng. 2013;115(2):200-6.
39. Chen J, Lin M, Foxe JJ, Pedrosa E, Hrabovsky A, Carroll R, et al. Transcriptome comparison of human neurons generated using induced pluripotent stem cells derived from dental pulp and skin fibroblasts. PLoS One. 2013;8(10):e75682.
40. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, Salzberg SL. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 2013;14(4):R36.
41. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012;22(9):1760-74.
42. Wang P, Lin M, Pedrosa E, Hrabovsky A, Zhang Z, Guo W, et al. CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in neurodevelopment. Mol Autism. 2015;6:55. doi: 10.1186/s13229-015-0048-6.
43. Leek JT JW, Parker HS, Fertig EJ, Jaffe AE, Storey JD. sva: Surrogate Variable Analysis. R package version 3120. 2016.
44. Agalliu D, Schieren I. Heterogeneity in the developmental potential of motor neuron progenitors revealed by clonal analysis of single cells in vitro. Neural Dev. 2009;4(1):2.
45. Suslov ON, Kukekov VG, Ignatova TN, Steindler DA. Neural stem cell heterogeneity demonstrated by molecular phenotyping of clonal neurospheres. Proc Natl Acad Sci U S A. 2002;99(22):14506-11.
46. Dolmetsch R, Geschwind DH. The human brain in a dish: the promise of iPSC-derived neurons. Cell. 2011;145(6):831-4. doi: 10.1016/j.cell.2011.05.034.
47. Prilutsky D, Palmer NP, Smedemark-Margulies N, Schlaeger TM, Margulies DM, Kohane IS. iPSC-derived neurons as a higher-throughput readout for autism: promises and pitfalls. Trends Mol Med. 2014;20(2):91-104.
48. Topol A, Zhu S, Hartley BJ, English J, Hauberg ME, Tran N, et al. Dysregulation of miRNA-9 in a subset of schizophrenia patient-derived neural progenitor cells. Cell Rep. 2016;15(5):1024-36. doi: 10.1016/j.celrep.2016.03.090.
49. Darmanis S, Sloan SA, Zhang Y, Enge M, Caneda C, Shuer LM, et al. A survey of human brain transcriptome diversity at the single cell level. Proc Natl Acad Sci U S A. 2015;112(23):7285-90.
50. Lake BB, Ai R, Kaeser GE, Salathia NS, Yung YC, Liu R, et al. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain. Science. 2016;352(6293):1586-90. doi: 10.1126/science.aaf1204.
51. van de Leemput J, Boles NC, Kiehl TR, Corneo B, Lederman P, Menon V, et al. CORTECON: a temporal transcriptome analysis of in vitro human cerebral cortex development from human embryonic stem cells. Neuron. 2014;83(1):51-68.
52. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2. Genome Biology. 2014;15:550. doi: 10.1186/s13059-014-0550-8
53. Arion D, Unger T, Lewis DA, Levitt P, Mirnics K. Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry. 2007;62(7):711-21. doi: 10.1016/j.biopsych.2006.12.021.
54. Aston C, Jiang L, Sokolov BP. Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res. 2004;77(6):858-66. doi: 10.1002/jnr.20208.
55. Hakak Y, Walker JR, Li C, Wong WH, Davis KL, Buxbaum JD, et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci U S A. 2001;98(8):4746-51. doi: 10.1073/pnas.081071198.
56. Haroutunian V, Katsel P, Dracheva S, Stewart DG, Davis KL. Variations in oligodendrocyte-related gene expression across multiple cortical regions: implications for the pathophysiology of schizophrenia. Int J Neuropsychopharmacol. 2007;10(4):565-73. doi: 10.1017/S1461145706007310.
57. Jalbrzikowski M, Lazaro MT, Gao F, Huang A, Chow C, Geschwind DH, et al. Transcriptome profiling of peripheral blood in 22q11.2 deletion syndrome reveals functional pathways related to psychosis and autism spectrum disorder. PLoS One. 2015;10(7):e0132542. doi: 10.1371/journal.pone.0132542.
58. Maycox PR, Kelly F, Taylor A, Bates S, Reid J, Logendra R, et al. Analysis of gene expression in two large schizophrenia cohorts identifies multiple changes associated with nerve terminal function. Mol Psychiatry. 2009;14(12):1083-94. doi: 10.1038/mp.2009.18.
59. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Stat Soc Ser B (Stat Method). 1995;57:289-300.
60. Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics. 2008;9(1):559.
61. Chen J, Bardes EE, Aronow BJ, Jegga AG. ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res. 2009;37 suppl 2:W305-W11.
62. Da Wei Huang BTS, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2008;4(1):44-57.
63. Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1-13.
64. Gulsuner S, Walsh T, Watts AC, Lee MK, Thornton AM, Casadei S, et al. Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network. Cell. 2013;154(3):518-29.
65. Barabasi A-L, Oltvai ZN. Network biology: understanding the cell's functional organization. Nat Rev Genet. 2004;5(2):101-13.
66. Zhang B, Horvath S. A general framework for weighted gene co-expression network analysis. Stat Appl Genet Mol Biol. 2005;4:Article17. doi: 10.2202/1544-6115.1128.
67. Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091-3.
68. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498-504.
69. van Beveren NJ, Krab LC, Swagemakers S, Buitendijk G, Boot E, van der Spek P, et al. Functional gene-expression analysis shows involvement of schizophrenia-relevant pathways in patients with 22q11 deletion syndrome. PLoS One. 2012;7(3):e33473.
70. Sivagnanasundaram S, Fletcher D, Hubank M, Illingworth E, Skuse D, Scambler P. Differential gene expression in the hippocampus of the Df1/+ mice: a model for 22q11. 2 deletion syndrome and schizophrenia. Brain Res. 2007;1139:48-59.
71. Meechan D, Maynard T, Wu Y, Gopalakrishna D, Lieberman J, LaMantia A-S. Gene dosage in the developing and adult brain in a mouse model of 22q11 deletion syndrome. Mol Cell Neurosci. 2006;33(4):412-28.
72. Wakim LM, Gupta N, Mintern JD, Villadangos JA. Enhanced survival of lung tissue-resident memory CD8+ T cells during infection with influenza virus due to selective expression of IFITM3. Nat Immunol. 2013;14(3):238-45.
73. Zhang Y-H, Zhao Y, Li N, Peng Y-C, Giannoulatou E, Jin R-H, et al. Interferon-induced transmembrane protein-3 genetic variant rs12252-C is associated with severe influenza in Chinese individuals. Nat Commun. 2013;4:1418.
74. Everitt AR, Clare S, Pertel T, John SP, Wash RS, Smith SE, et al. IFITM3 restricts the morbidity and mortality associated with influenza. Nature. 2012;484(7395):519-23.
75. Carter C. Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii. Schizophr Bull. 2009;35(6):1163-82.
76. Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, et al. Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry. 2004;61(8):774-80.
77. Beneyto M, Abbott A, Hashimoto T, Lewis DA. Lamina-specific alterations in cortical GABAA receptor subunit expression in schizophrenia. Cereb Cortex. 2011;21(5):999-1011. doi: 10.1093/cercor/bhq169.
78. Volk DW, Lewis DA. Early developmental disturbances of cortical inhibitory neurons: contribution to cognitive deficits in schizophrenia. Schizophr Bull. 2014;40(5):952-7.
79. Heckers S, Konradi C. GABAergic mechanisms of hippocampal hyperactivity in schizophrenia. Schizophr Res. 2015;167(1-3):4-11. doi: 10.1016/j.schres.2014.09.041.
80. Benes FM. Building models for postmortem abnormalities in hippocampus of schizophrenics. Schizophr Res. 2015;167(1-3):73-83. doi: 10.1016/j.schres.2015.01.014.
81. Torkamani A, Dean B, Schork NJ, Thomas EA. Coexpression network analysis of neural tissue reveals perturbations in developmental processes in schizophrenia. Genome Res. 2010;20(4):403-12.
82. Chen C, Cheng L, Grennan K, Pibiri F, Zhang C, Badner JA, et al. Two gene co-expression modules differentiate psychotics and controls. Mol Psychiatry. 2012;18(12):1308-14.
83. Archinti M, Britto M, Eden G, Furlan F, Murphy R, Degryse B. The urokinase receptor in the central nervous system. CNS Neurol Disord Drug Targets. 2011;10(2):271-94.
84. Gondi CS, Kandhukuri N, Dinh DH, Gujrati M, Rao JS. Downregulation of uPAR and uPA activates caspase mediated apoptosis, inhibits the PI3k/AKT pathway. Int J Oncol. 2007;31(1):19.
85. Cinque P, Nebuloni M, Santovito ML, Price RW, Gisslen M, Hagberg L, et al. The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations. Ann Neurol. 2004;55(5):687-94.
86. Cunningham O, Campion S, Perry VH, Murray C, Sidenius N, Docagne F, et al. Microglia and the urokinase plasminogen activator receptor/uPA system in innate brain inflammation. Glia. 2009;57(16):1802-14.
87. Bononi A, Agnoletto C, De Marchi E, Marchi S, Patergnani S, Bonora M, et al. Protein kinases and phosphatases in the control of cell fate. Enzyme Res. 2011;2011:329098. doi: 10.4061/2011/329098.
88. Kalla C, Scheuermann MO, Kube I, Schlotter M, Mertens D, Döhner H, et al. Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: Evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B. Eur J Cancer. 2007;43(8):1328-35.
89. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics. 2013;14(1):128.
90. Cremer T, Cremer C. Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet. 2001;2(4):292-301.
91. Sexton T, Schober H, Fraser P, Gasser SM. Gene regulation through nuclear organization. Nat Struct Mol Biol. 2007;14(11):1049-55.
92. Dekker J. Gene regulation in the third dimension. Science. 2008;319(5871):1793-4.
93. Misteli T. Beyond the sequence: cellular organization of genome function. Cell. 2007;128(4):787-800.
94. Kosak ST, Groudine M. Form follows function: The genomic organization of cellular differentiation. Genes Dev. 2004;18(12):1371-84.
95. Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009;326(5950):289-93.
96. Blumenthal I, Ragavendran A, Erdin S, Klei L, Sugathan A, Guide JR, et al. Transcriptional Consequences of 16p11. 2 Deletion and Duplication in Mouse Cortex and Multiplex Autism Families. Am J Hum Genet. 2014;94(6):870-83.
97. Consortium SWGotPG. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421-7.
98. Consortium ISG, 2 WTCCC. Genome-wide association study implicates HLA-C*01: 02 as a risk factor at the major histocompatibility complex locus in schizophrenia. Biol Psychiatry. 2012;72(8):620-8.
99. Andreassen O, Harbo H, Wang Y, Thompson W, Schork A, Mattingsdal M, et al. Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci. Mol Psychiatry. 2015;20:207-14.
100. Barge-Schaapveld DQ, Maas SM, Polstra A, Knegt LC, Hennekam R. The atypical 16p11. 2 deletion: a not so atypical microdeletion syndrome? Am J Med Genet A. 2011;155(5):1066-72.
101. Shatz CJ. MHC class I: an unexpected role in neuronal plasticity. Neuron. 2009;64(1):40-5.
102. Zohar O, Reiter Y, Bennink JR, Lev A, Cavallaro S, Paratore S, et al. Cutting edge: MHC class I-Ly49 interaction regulates neuronal function. J Immunol. 2008;180(10):6447-51.
103. Goddard CA, Butts DA, Shatz CJ. Regulation of CNS synapses by neuronal MHC class I. Proc Natl Acad Sci U S A. 2007;104(16):6828-33.
104. Boulanger LM. MHC class I in activity-dependent structural and functional plasticity. Neuron Glia Biol. 2004;1(03):283-9.
105. Corriveau RA, Huh GS, Shatz CJ. Regulation of class I MHC gene expression in the developing and mature CNS by neural activity. Neuron. 1998;21(3):505-20.
106. Karayiorgou M, Simon TJ, Gogos JA. 22q11. 2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia. Nat Rev Neurosci. 2010;11(6):402-16.
107. Karayiorgou M, Gogos JA. The molecular genetics of the 22q11-associated schizophrenia. Mol Brain Res. 2004;132(2):95-104.
108. Eyo UB, Dailey ME. Microglia: key elements in neural development, plasticity, and pathology. J Neuroimmune Pharmacol. 2013;8(3):494-509.
109. Fatemi SH, Folsom TD. The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophr Bull. 2009;35(3):528-48. doi: 10.1093/schbul/sbn187.
110. Juraeva D, Haenisch B, Zapatka M, Frank J, Witt SH, Mühleisen TW, et al. Integrated pathway-based approach identifies association between genomic regions at CTCF and CACNB2 and schizophrenia. PLoS Genet. 2014;10(6):e1004345.
111. Obulesu M, Lakshmi MJ. Apoptosis in Alzheimer's disease: an understanding of the physiology, pathology and therapeutic avenues. Neurochem Res. 2014;39(12):2301-12.
112. Schapira AH, Olanow CW, Greenamyre JT, Bezard E. Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives. Lancet. 2014;384(9942):545-55.
113. Jarskog LF, Glantz LA, Gilmore JH, Lieberman JA. Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005;29(5):846-58.
114. Jarskog LF, Selinger ES, Lieberman JA, Gilmore JH. Apoptotic proteins in the temporal cortex in schizophrenia: high Bax/Bcl-2 ratio without caspase-3 activation. Am J Psychiatry. 2004;161(1):109-15.
115. Jarskog LF, Gilmore JH, Selinger ES, Lieberman JA. Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia. Biol Psychiatry. 2000;48(7):641-50.
116. Nadri C, Dean B, Scarr E, Agam G. GSK-3 parameters in postmortem frontal cortex and hippocampus of schizophrenic patients. Schizophr Res. 2004;71(2):377-82.
117. Sweatt JD. The neuronal MAP kinase cascade: a biochemical signal integration system subserving synaptic plasticity and memory. J Neurochem. 2001;76(1):1-10.
118. Kyosseva SV. Mitogen-activated protein kinase signaling. Int Rev Neurobiol. 2004;59(3):201-20.
119. Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 2006;58(11):621-31.
120. Cheung EC, Slack RS. Emerging role for ERK as a key regulator of neuronal apoptosis. Sci Signal. 2004;2004(251):e45.
121. Samuels IS, Karlo JC, Faruzzi AN, Pickering K, Herrup K, Sweatt JD, et al. Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function. J Neurosci. 2008;28(27):6983-95.
122. Funk AJ, McCullumsmith RE, Haroutunian V, Meador-Woodruff JH. Abnormal activity of the MAPK-and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia. Neuropsychopharmacology. 2011;37(4):896-905.
123. Kyosseva SV, Elbein AD, Griffin WST, Mrak RE, Lyon M, Karson CN. Mitogen-activated protein kinases in schizophrenia. Biol Psychiatry. 1999;46(5):689-96.
124. Benes F, Matzilevich D, Burke R, Walsh J. The expression of proapoptosis genes is increased in bipolar disorder, but not in schizophrenia. Mol Psychiatry. 2005;11(3):241-51.
125. Catts VS, Catts SV, McGrath JJ, Féron F, McLean D, Coulson EJ, et al. Apoptosis and schizophrenia: a pilot study based on dermal fibroblast cell lines. Schizophr Res. 2006;84(1):20-8.
126. Kornfeld SJ, Zeffren B, Christodoulou CS, Day NK, Cawkwell G, Good RA. DiGeorge anomaly: a comparative study of the clinical and immunologic characteristics of patients positive and negative by fluorescence in situ hybridization. J Allergy Clin Immunol. 2000;105(5):983-7.
127. Sullivan KE. Chromosome 22q11. 2 deletion syndrome: DiGeorge syndrome/velocardiofacial syndrome. Immunol Allergy Clin North Am. 2008;28(2):353-66.
128. Willsey AJ, Sanders SJ, Li M, Dong S, Tebbenkamp AT, Muhle RA, et al. Coexpression networks implicate human midfetal deep cortical projection neurons in the pathogenesis of autism. Cell. 2013;155(5):997-1007.
129. Meechan DW, Tucker ES, Maynard TM, LaMantia A-S. Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci U S A. 2009;106(38):16434-45.
130. Fan Y, Abrahamsen G, McGrath JJ, Mackay-Sim A. Altered cell cycle dynamics in schizophrenia. Biol Psychiatry. 2012;71(2):129-35.
131. Katsel P, Davis KL, Li C, Tan W, Greenstein E, Hoffman LBK, et al. Abnormal indices of cell cycle activity in schizophrenia and their potential association with oligodendrocytes. Neuropsychopharmacology. 2008;33(12):2993-3009.
132. Kang W, Wong LC, Shi S-H, Hébert JM. The transition from radial glial to intermediate progenitor cell is inhibited by FGF signaling during corticogenesis. J Neurosci. 2009;29(46):14571-80.
133. Sahara S, O'Leary DD. Fgf10 regulates transition period of cortical stem cell differentiation to radial glia controlling generation of neurons and basal progenitors. Neuron. 2009;63(1):48-62.
134. Gogos J, Santha M, Takacs Z, Beck KD, Luine V, Lucas LR, et al. The gene encoding proline dehydrogenase modulates sensorimotor gating in mice. Nat Genet. 1999;21(4):434-9.
135. Kazama H, Ichikawa A, Kohsaka H, Morimoto-Tanifuji T, Nose A. Innervation and activity dependent dynamics of postsynaptic oxidative metabolism. Neuroscience. 2008;152(1):40-9.
136. Huttenlocher PR. Synaptic density in human frontal cortex-developmental changes and effects of aging. Brain Res. 1979;163(2):195-205.
137. Rakic P, Bourgeois J-P, Eckenhoff MF, Zecevic N, Goldman-Rakic PS. Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science. 1986;232(4747):232-5.
138. Paterlini M, Zakharenko SS, Lai W-S, Qin J, Zhang H, Mukai J, et al. Transcriptional and behavioral interaction between 22q11. 2 orthologs modulates schizophrenia-related phenotypes in mice. Nat Neurosci. 2005;8(11):1586-94.