MicroRNAs as the cause of schizophrenia in 22q11.2 deletion carriers, and possible implications for idiopathic disease: a mini-review

The 22q11.2 deletion is the strongest known genetic risk factor for schizophrenia. Research has implicated microRNA-mediated dysregulation in 22q11.2 deletion syndrome (22q11.2DS) schizophrenia-risk. Primary candidate genes are DGCR8 (DiGeorge syndrome critical region gene 8), which encodes a component of the microprocessor complex essential for microRNA biogenesis, and MIR185, which encodes microRNA 185. Mouse models of 22q11.2DS have demonstrated alterations in brain microRNA biogenesis, and that DGCR8 haploinsufficiency may contribute to these alterations, e.g., via down-regulation of a specific microRNA subset. miR-185 was the top-scoring down-regulated microRNA in both the prefrontal cortex and the hippocampus, brain areas which are the key foci of schizophrenia research. This reduction in miR-185 expression contributed to dendritic and spine development deficits in hippocampal neurons. In addition, miR-185 has two validated targets (RhoA, Cdc42), both of which have been associated with altered expression levels in schizophrenia. These combined data support the involvement of miR-185 and its down-stream pathways in schizophrenia. This review summarizes evidence implicating microRNA-mediated dysregulation in schizophrenia in both 22q11.2DS-related and idiopathic cases.

[1]  K. Kosik,et al.  Specific MicroRNAs Modulate Embryonic Stem Cell–Derived Neurogenesis , 2006, Stem cells.

[2]  Peter J. Scambler,et al.  22q11.2 deletion syndrome. , 2015, Nature reviews. Disease primers.

[3]  Vetle I. Torvik,et al.  Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain , 2008, Journal of neurochemistry.

[4]  G. Schratt.  microRNAs at the synapse , 2011, Nature Reviews Cancer.

[5]  J. Reményi,et al.  miR-132/212 Knockout Mice Reveal Roles for These miRNAs in Regulating Cortical Synaptic Transmission and Plasticity , 2013, PloS one.

[6]  Lin He,et al.  MicroRNAs: small RNAs with a big role in gene regulation , 2004, Nature Reviews Genetics.

[7]  Agnieszka Bronisz,et al.  Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. , 2008, Cancer research.

[8]  G. Schratt,et al.  Dopamine-Regulated MicroRNA MiR-181a Controls GluA2 Surface Expression in Hippocampal Neurons , 2011, Molecular and Cellular Biology.

[9]  Sarah A. Stern,et al.  A critical role for IGF-II in memory consolidation and enhancement , 2011, Nature.

[10]  I. Dozmorov,et al.  Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome. , 2013, Clinical immunology.

[11]  T. Sun,et al.  MicroRNA-92b regulates the development of intermediate cortical progenitors in embryonic mouse brain , 2013, Proceedings of the National Academy of Sciences.

[12]  C. Nobes,et al.  Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia , 1995, Cell.

[13]  Oliver Hobert,et al.  A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans , 2003, Nature.

[14]  D. Watanabe,et al.  MiR-124 a is required for hippocampal axogenesis and retinal cone survival through Lhx 2 suppression , 2011 .

[15]  Paul Pavlidis,et al.  Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model , 2008, Nature Genetics.

[16]  J. Lieberman,et al.  The genome-wide supported microRNA-137 variant predicts phenotypic heterogeneity within schizophrenia , 2013, Molecular Psychiatry.

[17]  S. Minoshima,et al.  Role of TBX1 in human del22q11.2 syndrome , 2003, The Lancet.

[18]  Hua Su,et al.  MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. , 2010, Cell stem cell.

[19]  A. Mechelli,et al.  Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state. , 2009, Brain : a journal of neurology.

[20]  Ivan Nikolov,et al.  Fine mapping of ZNF 804 A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder , 2011 .

[21]  T. Maniatis,et al.  The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. , 2007, Molecular cell.

[22]  Bin Xu,et al.  Derepression of a Neuronal Inhibitor due to miRNA Dysregulation in a Schizophrenia-Related Microdeletion , 2013, Cell.

[23]  Beverly L. Davidson,et al.  MiR-34a Represses Numbl in Murine Neural Progenitor Cells and Antagonizes Neuronal Differentiation , 2012, PloS one.

[24]  C. Bearden,et al.  Converging levels of analysis on a genomic hotspot for psychosis: Insights from 22q11.2 Deletion Syndrome , 2013, Neuropharmacology.

[25]  Cheol‐Hee Kim,et al.  Mind bomb is a ubiquitin ligase that is essential for efficient activation of Notch signaling by Delta. , 2003, Developmental cell.

[26]  M. Sur,et al.  miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity. , 2011, Nature neuroscience.

[27]  P. Callaerts,et al.  miRNA genes and the brain: implications for psychiatric disorders a , 2010, Human mutation.

[28]  Akira Sawa,et al.  Schizophrenia: Diverse Approaches to a Complex Disease , 2002, Science.

[29]  L. Tsai,et al.  Validation of schizophrenia-associated genes CSMD1, C10orf26, CACNA1C and TCF4 as miR-137 targets , 2013, Molecular Psychiatry.

[30]  Joseph A. Gogos,et al.  Palmitoylation-dependent neurodevelopmental deficits in a mouse model of the 22q11 microdeletion , 2008, Nature Neuroscience.

[31]  R. Miranda,et al.  Competing Interactions between Micro-RNAs Determine Neural Progenitor Survival and Proliferation after Ethanol Exposure: Evidence from an Ex Vivo Model of the Fetal Cerebral Cortical Neuroepithelium , 2007, The Journal of Neuroscience.

[32]  M. Cairns,et al.  Dysregulation of miRNA 181b in the temporal cortex in schizophrenia. , 2008, Human molecular genetics.

[33]  Ann Y. Nakayama,et al.  Small GTPases Rac and Rho in the Maintenance of Dendritic Spines and Branches in Hippocampal Pyramidal Neurons , 2000, The Journal of Neuroscience.

[34]  B. Roe,et al.  Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: genomic organization and deletion endpoint analysis. , 2000, Human molecular genetics.

[35]  M. Götz,et al.  PH‐Domain‐driven targeting of collybistin but not Cdc42 activation is required for synaptic gephyrin clustering , 2010, The European journal of neuroscience.

[36]  R. Shprintzen,et al.  Defining the clinical spectrum of deletion 22q11.2. , 2005, The Journal of pediatrics.

[37]  M. Chopp,et al.  The MicroRNA-17–92 Cluster Enhances Axonal Outgrowth in Embryonic Cortical Neurons , 2013, The Journal of Neuroscience.

[38]  S. Warren,et al.  Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signaling. , 2011, Molecular cell.

[39]  S. Aizawa,et al.  MicroRNA-9 Modulates Cajal–Retzius Cell Differentiation by Suppressing Foxg1 Expression in Mouse Medial Pallium , 2008, The Journal of Neuroscience.

[40]  Alessandro Coatti,et al.  Experience-dependent expression of miR132 regulates ocular dominance plasticity , 2011, Nature Neuroscience.

[41]  A. Bordey,et al.  miR-132 Enhances Dendritic Morphogenesis, Spine Density, Synaptic Integration, and Survival of Newborn Olfactory Bulb Neurons , 2012, PloS one.

[42]  Yi Xing,et al.  The Bifunctional microRNA miR-9/miR-9* Regulates REST and CoREST and Is Downregulated in Huntington's Disease , 2008, The Journal of Neuroscience.

[43]  J. Nurnberger,et al.  Identification of blood biomarkers for psychosis using convergent functional genomics , 2011, Molecular Psychiatry.

[44]  P. Kenny,et al.  MicroRNAs in neuronal function and dysfunction , 2012, Trends in Neurosciences.

[45]  Giuseppe Basso,et al.  MiR-34a Targeting of Notch Ligand Delta-Like 1 Impairs CD15+/CD133+ Tumor-Propagating Cells and Supports Neural Differentiation in Medulloblastoma , 2011, PloS one.

[46]  Thomas W. Mühleisen,et al.  Large recurrent microdeletions associated with schizophrenia , 2008, Nature.

[47]  P. Jin,et al.  MicroRNA miR‐137 Regulates Neuronal Maturation by Targeting Ubiquitin Ligase Mind Bomb‐1 , 2010, Stem cells.

[48]  Tony J. Simon,et al.  22q11.2 microdeletions: linking DNA structural variation to brain dysfunction and schizophrenia , 2010, Nature Reviews Neuroscience.

[49]  G. Crabtree,et al.  MicroRNA-mediated switching of chromatin-remodelling complexes in neural development , 2009, Nature.

[50]  Michael T. McManus,et al.  Conditional Loss of Dicer Disrupts Cellular and Tissue Morphogenesis in the Cortex and Hippocampus , 2008, The Journal of Neuroscience.

[51]  Bin Xu,et al.  MicroRNAs in psychiatric and neurodevelopmental disorders , 2010, Brain Research.

[52]  C. Shen,et al.  Modulation of mGluR-Dependent MAP1B Translation and AMPA Receptor Endocytosis by MicroRNA miR-146a-5p , 2013, The Journal of Neuroscience.

[53]  Takanobu Nakazawa,et al.  microRNA Modulation of Circadian-Clock Period and Entrainment , 2007, Neuron.

[54]  Gail Mandel,et al.  microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus , 2010, Proceedings of the National Academy of Sciences.

[55]  Yuanjia Tang,et al.  miR-132 regulates the differentiation of dopamine neurons by directly targeting Nurr1 expression , 2012, Journal of Cell Science.

[56]  Jianxin Shi,et al.  Copy number variants in schizophrenia: confirmation of five previous findings and new evidence for 3q29 microdeletions and VIPR2 duplications. , 2011, The American journal of psychiatry.

[57]  C. Coulson,et al.  Molecular Architecture , 1953, Nature.

[58]  S. Impey,et al.  miRNA-132: a dynamic regulator of cognitive capacity , 2012, Brain Structure and Function.

[59]  Robert Blelloch,et al.  Monoallelic deletion of the microRNA biogenesis gene Dgcr8 produces deficits in the development of excitatory synaptic transmission in the prefrontal cortex , 2011, Neural Development.

[60]  Anton J. Enright,et al.  Human MicroRNA Targets , 2004, PLoS biology.

[61]  J. Jakobsson,et al.  Functional Studies of microRNAs in Neural Stem Cells: Problems and Perspectives , 2012, Front. Neurosci..

[62]  Hsien-Ting Huang,et al.  In vivo knockdown of hippocampal miR‐132 expression impairs memory acquisition of trace fear conditioning , 2013, Hippocampus.

[63]  M. Segura,et al.  microRNAs as pharmacological targets in cancer. , 2013, Pharmacological research.

[64]  Anders D. Børglum,et al.  Genome-wide association study identifies five new schizophrenia loci , 2011, Nature Genetics.

[65]  D. Watanabe,et al.  miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression , 2011, Nature Neuroscience.

[66]  C. Stigloher,et al.  MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary , 2008, Nature Neuroscience.

[67]  G. Westbrook,et al.  miR-132 Mediates the Integration of Newborn Neurons into the Adult Dentate Gyrus , 2011, PloS one.

[68]  B. Morrow,et al.  Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. , 1999, American journal of human genetics.

[69]  P. Visscher,et al.  Rare chromosomal deletions and duplications increase risk of schizophrenia , 2008, Nature.

[70]  Hiroshi Kiyonari,et al.  MicroRNA-9 Regulates Neurogenesis in Mouse Telencephalon by Targeting Multiple Transcription Factors , 2011, The Journal of Neuroscience.

[71]  F. Slack,et al.  The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure , 2008, Cell cycle.

[72]  T. Mak,et al.  Neuronal differentiation by TAp73 is mediated by microRNA-34a regulation of synaptic protein targets , 2011, Proceedings of the National Academy of Sciences.

[73]  Hideaki Ando,et al.  An activity-induced microRNA controls dendritic spine formation by regulating Rac1-PAK signaling , 2010, Molecular and Cellular Neuroscience.

[74]  Kihwan Lee,et al.  An Activity-Regulated microRNA, miR-188, Controls Dendritic Plasticity and Synaptic Transmission by Downregulating Neuropilin-2 , 2012, The Journal of Neuroscience.

[75]  Lin He,et al.  MicroRNAs: small RNAs with a big role in gene regulation , 2004, Nature reviews genetics.

[76]  Wei Li,et al.  MicroRNA regulation of homeostatic synaptic plasticity , 2011, Proceedings of the National Academy of Sciences.

[77]  Steven W. Flavell,et al.  Mef2-mediated transcription of the miR379–410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels , 2009, The EMBO journal.

[78]  M. Peschanski,et al.  miR-125 potentiates early neural specification of human embryonic stem cells , 2012, Development.

[79]  Pasko Rakic,et al.  Human-specific regulation of MeCP2 levels in fetal brains by microRNA miR-483-5p. , 2013, Genes & development.

[80]  Sean J. Morrison,et al.  Hmga2 Promotes Neural Stem Cell Self-Renewal in Young but Not Old Mice by Reducing p16Ink4a and p19Arf Expression , 2008, Cell.

[81]  M. Cairns,et al.  Down-regulation of miR-17 family expression in response to retinoic acid induced neuronal differentiation. , 2009, Cellular signalling.

[82]  A. Schier,et al.  Members of the miRNA-200 Family Regulate Olfactory Neurogenesis , 2008, Neuron.

[83]  Michael E. Greenberg,et al.  A brain-specific microRNA regulates dendritic spine development , 2006, Nature.

[84]  Feng-Quan Zhou,et al.  MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration. , 2013, Genes & development.

[85]  R. Shprintzen,et al.  Schizophrenia susceptibility associated with interstitial deletions of chromosome 22q11. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[86]  Jan Baumgart,et al.  miR‐124‐regulated RhoG reduces neuronal process complexity via ELMO/Dock180/Rac1 and Cdc42 signalling , 2012, The EMBO journal.

[87]  Bin Xu,et al.  The 22q11.2 microdeletion: Fifteen years of insights into the genetic and neural complexity of psychiatric disorders , 2011, International Journal of Developmental Neuroscience.

[88]  A. Bassett,et al.  Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome , 2011, Behavior genetics.

[89]  K. Kosik,et al.  MicroRNAs Potentiate Neural Development , 2009, Neuron.

[90]  L. Johnston,et al.  Temporal Regulation of Metamorphic Processes in Drosophila by the let-7 and miR-125 Heterochronic MicroRNAs , 2008, Current Biology.

[91]  T. Iwamoto,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 , 2013, The Journal of Neuroscience.

[92]  M. Sheng,et al.  Molecular mechanisms of dendritic spine morphogenesis , 2006, Current Opinion in Neurobiology.

[93]  L. Smirnova,et al.  A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment , 2008, Nature Cell Biology.

[94]  Z. Bashir,et al.  MicroRNA-132 regulates recognition memory and synaptic plasticity in the perirhinal cortex , 2012, The European journal of neuroscience.

[95]  L. Tsai,et al.  A novel pathway regulates memory and plasticity via SIRT1 and miR-134 , 2010, Nature.

[96]  J. Mukai,et al.  Palmitoylation-dependent neurodevelopmental deficits in a mouse model of 22q11 microdeletion , 2009, Neuroscience Research.

[97]  A. Schier,et al.  Target Protectors Reveal Dampening and Balancing of Nodal Agonist and Antagonist by miR-430 , 2007, Science.

[98]  Lorenzo D Botto,et al.  A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. , 2003, Pediatrics.

[99]  Robert C. Thompson,et al.  MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation. , 2008, Experimental cell research.

[100]  Stanislav S Zakharenko,et al.  Age-Dependent MicroRNA Control of Synaptic Plasticity in 22q11 Deletion Syndrome and Schizophrenia , 2012, The Journal of Neuroscience.

[101]  P. Sharp,et al.  Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125 b and miR-132 , 2010 .

[102]  R. Myers,et al.  Analysis of miR-137 expression and rs1625579 in dorsolateral prefrontal cortex. , 2013, Journal of psychiatric research.

[103]  Y. Yamaguchi,et al.  EphB receptors regulate dendritic spine development via intersectin, Cdc42 and N-WASP , 2002, Nature Neuroscience.

[104]  Danny S. Park,et al.  Genetic architecture of microRNA expression: implications for the transcriptome and complex traits. , 2012, American journal of human genetics.

[105]  Guoqiang Sun,et al.  MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling , 2010, Proceedings of the National Academy of Sciences.

[106]  T. Reid,et al.  Identification and Characterization of hPEM-2, a Guanine Nucleotide Exchange Factor Specific for Cdc42* , 1999, The Journal of Biological Chemistry.

[107]  T. Hashimoto,et al.  Molecular mechanisms contributing to dendritic spine alterations in the prefrontal cortex of subjects with schizophrenia , 2006, Molecular Psychiatry.

[108]  A. Bassett,et al.  Neurocognitive profile in 22q11 deletion syndrome and schizophrenia , 2006, Schizophrenia Research.

[109]  Ramkumar Veppathur Mohan,et al.  MicroRNAs as pharmacological targets in diabetes. , 2013, Pharmacological research.

[110]  Bin Xu,et al.  Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex , 2011, Proceedings of the National Academy of Sciences.

[111]  R. Kucherlapati,et al.  Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients. , 1997, American journal of human genetics.

[112]  C. Spencer,et al.  Identification of loci associated with schizophrenia by genome-wide association and follow-up , 2008, Nature Genetics.

[113]  P. Barbry,et al.  miR-7a regulation of Pax6 controls spatial origin of forebrain dopaminergic neurons , 2012, Nature Neuroscience.

[114]  Vladimir I. Vladimirov,et al.  Experimental validation of candidate schizophrenia gene ZNF804A as target for hsa-miR-137 , 2012, Schizophrenia Research.

[115]  Yi Zheng,et al.  miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells. , 2011, Cancer letters.

[116]  David A. Lewis,et al.  Altered Cortical CDC42 Signaling Pathways in Schizophrenia: Implications for Dendritic Spine Deficits , 2010, Biological Psychiatry.

[117]  Jae W. Lee,et al.  The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. , 2007, Genes & development.

[118]  Jong H. Yoon,et al.  Prefrontal cortical deficits and impaired cognition-emotion interactions in schizophrenia. , 2011, The American journal of psychiatry.

[119]  Sandro Banfi,et al.  microRNAs and genetic diseases , 2009, PathoGenetics.

[120]  M. Greenberg,et al.  A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis , 2009, Nature Cell Biology.

[121]  Wieland B Huttner,et al.  Convergent repression of Foxp2 3′UTR by miR-9 and miR-132 in embryonic mouse neocortex: implications for radial migration of neurons , 2012, Development.

[122]  I. Bozzoni,et al.  Stress induces region specific alterations in microRNAs expression in mice , 2010, Behavioural Brain Research.

[123]  Silke Szymczak,et al.  Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility , 2010, PloS one.

[124]  C. Ren,et al.  MicroRNA-137 represses Klf4 and Tbx3 during differentiation of mouse embryonic stem cells. , 2013, Stem cell research.

[125]  S. Sokol,et al.  PAR-1 phosphorylates Mind bomb to promote vertebrate neurogenesis. , 2009, Developmental cell.

[126]  M. Owen,et al.  High rates of schizophrenia in adults with velo-cardio-facial syndrome (VCFS) , 1999, Schizophrenia Research.

[127]  Michele Zoli,et al.  Targeting of the Arpc3 actin nucleation factor by miR-29a/b regulates dendritic spine morphology , 2011, The Journal of cell biology.

[128]  Olga Varlamova,et al.  A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[129]  Anne S. Bassett,et al.  miRNA-mediated risk for schizophrenia in 22q11.2 deletion syndrome , 2012, Front. Gene..

[130]  Emmette R. Hutchison,et al.  miR-375 Inhibits Differentiation of Neurites by Lowering HuD Levels , 2010, Molecular and Cellular Biology.

[131]  E. Mazzoni,et al.  Mir-17-3p Controls Spinal Neural Progenitor Patterning by Regulating Olig2/Irx3 Cross-Repressive Loop , 2011, Neuron.

[132]  N. Perrone-Bizzozero,et al.  Degradation of high affinity HuD targets releases Kv1.1 mRNA from miR-129 repression by mTORC1 , 2013, The Journal of cell biology.

[133]  M. Geyer,et al.  Prepulse inhibition and genetic mouse models of schizophrenia , 2009, Behavioural Brain Research.

[134]  Guoqiang Sun,et al.  A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination , 2009, Nature Structural &Molecular Biology.

[135]  I. Bozzoni,et al.  Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells , 2008, The EMBO journal.

[136]  Li Li,et al.  MicroRNA-mediated conversion of human fibroblasts to neurons , 2011, Nature.

[137]  Yang Zhou,et al.  Effects of miR‐541 on neurite outgrowth during neuronal differentiation , 2011, Cell biochemistry and function.

[138]  H. Sticht,et al.  Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions. , 2007, American journal of human genetics.

[139]  P. Deloukas,et al.  Common Regulatory Variation Impacts Gene Expression in a Cell Type–Dependent Manner , 2009, Science.

[140]  P. Zamore,et al.  MicroRNA Biogenesis: Drosha Can't Cut It without a Partner , 2005, Current Biology.

[141]  Alissa M. Weaver,et al.  N-WASP and the Arp2/3 Complex Are Critical Regulators of Actin in the Development of Dendritic Spines and Synapses* , 2008, Journal of Biological Chemistry.

[142]  Oliver Hobert,et al.  Molecular architecture of a miRNA-regulated 3' UTR. , 2008, RNA.

[143]  L. Tsai,et al.  Neuronal Morphogenesis Is Regulated by the Interplay between Cyclin-Dependent Kinase 5 and the Ubiquitin Ligase Mind Bomb 1 , 2007, The Journal of Neuroscience.

[144]  Patrick F. Sullivan,et al.  Genetic architectures of psychiatric disorders: the emerging picture and its implications , 2012, Nature Reviews Genetics.

[145]  G. Hannon,et al.  A MicroRNA Feedback Circuit in Midbrain Dopamine Neurons , 2007, Science.

[146]  Fabian J Theis,et al.  A Unilateral Negative Feedback Loop Between miR-200 microRNAs and Sox2/E2F3 Controls Neural Progenitor Cell-Cycle Exit and Differentiation , 2012, The Journal of Neuroscience.

[147]  M. Webster,et al.  Association between SNPs and gene expression in multiple regions of the human brain , 2012, Translational Psychiatry.

[148]  P. Falkai,et al.  microRNA‐34c is a novel target to treat dementias , 2011, The EMBO journal.

[149]  Hideaki Ando,et al.  An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP , 2008, Proceedings of the National Academy of Sciences.

[150]  D. Rujescu,et al.  Fine mapping of ZNF804A and genome-wide significant evidence for its involvement in schizophrenia and bipolar disorder , 2011, Molecular Psychiatry.

[151]  Lennart Opitz,et al.  A hippocampal insulin‐growth factor 2 pathway regulates the extinction of fear memories , 2011, The EMBO journal.

[152]  A. Wagner,et al.  The hippocampal formation in schizophrenia. , 2010, The American journal of psychiatry.