Frontiers in Biology

, Volume 5, Issue 4, pp 304–323 | Cite as

Epigenetic regulation of neuronal dendrite and dendritic spine development

  • Richard D. Smrt
  • Xinyu Zhao


Dendrites and the dendritic spines of neurons play key roles in the connectivity of the brain and have been recognized as the locus of long-term synaptic plasticity, which is correlated with learning and memory. The development of dendrites and spines in the mammalian central nervous system is a complex process that requires specific molecular events over a period of time. It has been shown that specific molecules are needed not only at the spine’s point of contact, but also at a distance, providing signals that initiate a cascade of events leading to synapse formation. The specific molecules that act to signal neuronal differentiation, dendritic morphology, and synaptogenesis are tightly regulated by genetic and epigenetic programs. It has been shown that the dendritic spine structure and distribution are altered in many diseases, including many forms of mental retardation (MR), and can also be potentiated by neuronal activities and an enriched environment. Because dendritic spine pathologies are found in many types of MR, it has been proposed that an inability to form normal spines leads to the cognitive and motor deficits that are characteristic of MR. Epigenetic mechanisms, including DNA methylation, chromatin remodeling, and the noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. The study of epigenetics focuses on cellular effects that result in a heritable pattern of gene expression without changes to genomic encoding. Despite extensive efforts to understand the molecular regulation of dendrite and spine development, epigenetic mechanisms have only recently been considered. In this review, we will focus on epigenetic mechanisms that regulate the development and maturation of dendrites and spines. We will discuss how epigenetic alterations could result in spine abnormalities that lead to MR, such as is seen in fragile X and Rett syndromes. We will also discuss both general methodology and recent technological advances in the study of neuronal dendrites and spines.


epigenetics neurodevelopment dendritic spine synapse microRNA methyl-CpG binding protein 2 (MeCP2) mental retardation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Akbarian S, Chen R Z, Gribnau J, Rasmussen T P, Fong H, Jaenisch R, Jones E G (2001). Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal cortex. Neurobiol Dis, 8(5): 784–791PubMedCrossRefGoogle Scholar
  2. Alvarez V A, Sabatini B L (2007). Anatomical and physiological plasticity of dendritic spines. Annu Rev Neurosci, 30: 79–97PubMedCrossRefGoogle Scholar
  3. Amir R E, Van den Veyver I B, Wan M, Tran C Q, Francke U, Zoghbi H Y (1999). Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet, 23(2): 185–188PubMedCrossRefGoogle Scholar
  4. Antar L N, Afroz R, Dictenberg J B, Carroll R C, Bassell G J (2004). Metabotropic glutamate receptor activation regulates fragile x mental retardation protein and FMR1 mRNA localization differentially in dendrites and at synapses. J Neurosci, 24(11): 2648–2655PubMedCrossRefGoogle Scholar
  5. Antar L N, Dictenberg J B, Plociniak M, Afroz R, Bassell G J (2005). Localization of FMRP-associated mRNA granules and requirement of microtubules for activity-dependent trafficking in hippocampal neurons. Genes Brain Behav, 4(6): 350–359PubMedCrossRefGoogle Scholar
  6. Armstrong D, Dunn J K, Antalffy B, Trivedi R (1995). Selective dendritic alterations in the cortex of Rett syndrome. J Neuropathol Exp Neurol, 54(2): 195–201PubMedCrossRefGoogle Scholar
  7. Armstrong D D (2002). Neuropathology of Rett syndrome. Ment Retard Dev Disabil Res Rev, 8(2): 72–76PubMedCrossRefGoogle Scholar
  8. Ashley C T, Sutcliffe J S, Kunst C B, Leiner H A, Eichler E E, Nelson D L, Warren S T (1993). Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. Nat Genet, 4(3): 244–251PubMedCrossRefGoogle Scholar
  9. Ashraf S I, McLoon A L, Sclarsic SM, Kunes S (2006). Synaptic protein synthesis associated with memory is regulated by the RISC pathway in Drosophila. Cell, 124(1): 191–205PubMedCrossRefGoogle Scholar
  10. Azuara V, Perry P, Sauer S, Spivakov M, Jørgensen H F, John R M, Gouti M, Casanova M, Warnes G, Merkenschlager M, Fisher A G (2006). Chromatin signatures of pluripotent cell lines. Nat Cell Biol, 8(5): 532–538PubMedCrossRefGoogle Scholar
  11. Bagni C, Greenough W T (2005). From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome. Nat Rev Neurosci, 6(5): 376–387PubMedCrossRefGoogle Scholar
  12. Bakker C E, Verheij C, Willemsen R, Helm R, Oerlemans F, Vermey M, Bygrave A, Hoogeveen A, Oostr B A, Reyniers E, De Boule K, D’Hooge R, Cras P, van Velzen D, Nagels G, Martin J J, De Deyn P P, Darby J K, Willems P J (1994). Fmr1 knockout mice: a model to study fragile X mental retardation. Cell, 78(1): 23–33Google Scholar
  13. Balasubramaniyan V, Boddeke E, Bakels R, Küst B, Kooistra S, Veneman A, Copray S (2006). Effects of histone deacetylation inhibition on neuronal differentiation of embryonic mouse neural stem cells. Neuroscience, 143(4): 939–951PubMedCrossRefGoogle Scholar
  14. Barbato C, Giorgi C, Catalanotto C, Cogoni C (2008). Thinking about RNA? MicroRNAs in the brain. Mamm Genome, 19(7–8): 541–551PubMedCrossRefGoogle Scholar
  15. Barreto G, Schäfer A, Marhold J, Stach D, Swaminathan S K, Handa V, Döderlein G, Maltry N, Wu W, Lyko F, Niehrs C (2007). Gadd45a promotes epigenetic gene activation by repair-mediated DNA demethylation. Nature, 445(7128): 671–675PubMedCrossRefGoogle Scholar
  16. Barski A, Cuddapah S, Cui K, Roh T Y, Schones D E, Wang Z, Wei G, Chepelev I, Zhao K (2007). High-resolution profiling of histone methylations in the human genome. Cell, 129(4): 823–837PubMedCrossRefGoogle Scholar
  17. Bassell G J, Warren S T (2008). Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron, 60(2): 201–214PubMedCrossRefGoogle Scholar
  18. Battaglia A (2005). The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. Brain Dev, 27(5): 365–369PubMedCrossRefGoogle Scholar
  19. Belichenko P V, Hagberg B, Dahlström A (1997). Morphological study of neocortical areas in Rett syndrome. Acta Neuropathol, 93(1): 50–61PubMedCrossRefGoogle Scholar
  20. Belichenko P V, Masliah E, Kleschevnikov A M, Villar A J, Epstein C J, Salehi A, Mobley W C (2004). Synaptic structural abnormalities in the Ts65Dn mouse model of Down Syndrome. J Comp Neurol, 480(3): 281–298PubMedCrossRefGoogle Scholar
  21. Belichenko P V, Oldfors A, Hagberg B, Dahlström A (1994). Rett syndrome: 3-D confocal microscopy of cortical pyramidal dendrites and afferents. Neuroreport, 5(12): 1509–1513PubMedCrossRefGoogle Scholar
  22. Benzer S (1967). Behavioral mutants of drosophila isolated by countercurrent distribution. Proc Natl Acad Sci U S A, 58(3): 1112–1119PubMedCrossRefGoogle Scholar
  23. Berg J S, Brunetti-Pierri N, Peters S U, Kang S H, Fong C T, Salamone J, Freedenberg D, Hannig V L, Prock L A, Miller D T, Raffalli P, Harris D J, Erickson R P, Cunniff C, Clark G D, Blazo M A, Peiffer D A, Gunderson K L, Sahoo T, Patel A, Lupski J R, Beaudet A L, Cheung S W (2007). Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region. Genet Med, 9(7): 427–441PubMedCrossRefGoogle Scholar
  24. Bernstein B E, Meissner A, Lander E S (2007). The mammalian epigenome. Cell, 128(4): 669–681PubMedCrossRefGoogle Scholar
  25. Bernstein B E, Mikkelsen T S, Xie X, Kamal M, Huebert D J, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber S L, Lander E S (2006). A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell, 125(2): 315–326PubMedCrossRefGoogle Scholar
  26. Bestor T H (2000). The DNA methyltransferases of mammals. Hum Mol Genet, 9(16): 2395–2402PubMedCrossRefGoogle Scholar
  27. Bestor T H, Tycko B (1996). Creation of genomic methylation patterns. Nat Genet, 12(4): 363–367PubMedCrossRefGoogle Scholar
  28. Bhattacharya S K, Ramchandani S, Cervoni N, Szyf M (1999). A mammalian protein with specific demethylase activity for mCpG DNA. Nature, 397(6720): 579–583PubMedCrossRefGoogle Scholar
  29. Bienvenu T, Chelly J (2006). Molecular genetics of Rett syndrome: when DNA methylation goes unrecognized. Nat Rev Genet, 7(6): 415–426PubMedCrossRefGoogle Scholar
  30. Bird A (2002). DNA methylation patterns and epigenetic memory. Genes Dev, 16(1): 6–21PubMedCrossRefGoogle Scholar
  31. Bourne J N, Sorra K E, Hurlburt J, Harris K M (2007). Polyribosomes are increased in spines of CA1 dendrites 2 h after the induction of LTP in mature rat hippocampal slices. Hippocampus, 17(1): 1–4PubMedCrossRefGoogle Scholar
  32. Boyer L A, Plath K, Zeitlinger J, Brambrink T, Medeiros L A, Lee T I, Levine S S, Wernig M, Tajonar A, Ray M K, Bell G W, Otte A P, Vidal M, Gifford D K, Young R A, Jaenisch R (2006). Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature, 441(7091): 349–353PubMedCrossRefGoogle Scholar
  33. Brennecke J, Hipfner D R, Stark A, Russell R B, Cohen S M (2003). bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell, 113(1): 25–36PubMedCrossRefGoogle Scholar
  34. Busard H L, Renier WO, Gabreëls F J, Jaspar H H, Slooff J L, Janssen A J, Van Haelst U J (1987). Lafora disease: a quantitative morphological and biochemical study of the cerebral cortex. Clin Neuropathol, 6(1): 1–6PubMedGoogle Scholar
  35. Bushati N, Cohen SM (2007). microRNA functions. Annu Rev Cell Dev Biol, 23: 175–205PubMedCrossRefGoogle Scholar
  36. Cajal S R (1891). Sur la structure de l’ecorce cérébrale de quelques mammifères. Cellule, 7: 125–176Google Scholar
  37. Caudy A A, Myers M, Hannon G J, Hammond S M (2002). Fragile Xrelated protein and VIG associate with the RNA interference machinery. Genes Dev, 16(19): 2491–2496PubMedCrossRefGoogle Scholar
  38. Chahrour M, Zoghbi H Y (2007). The story of Rett syndrome: from clinic to neurobiology. Neuron, 56(3): 422–437PubMedCrossRefGoogle Scholar
  39. Chang S, Bray SM, Li Z, Zarnescu D C, He C, Jin P, Warren S T (2008). Identification of small molecules rescuing fragile X syndrome phenotypes in Drosophila. Nat Chem Biol, 4(4): 256–263PubMedCrossRefGoogle Scholar
  40. Chang S, Johnston R J Jr, Frøkjaer-Jensen C, Lockery S, Hobert O (2004). MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature, 430(7001): 785–789PubMedCrossRefGoogle Scholar
  41. Chen C Z, Li L, Lodish H F, Bartel D P (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science, 303(5654): 83–86PubMedCrossRefGoogle Scholar
  42. Chen L, Toth M (2001). Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience, 103(4): 1043–1050PubMedCrossRefGoogle Scholar
  43. Chen R Z, Akbarian S, Tudor M, Jaenisch R (2001). Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet, 27(3): 327–331PubMedCrossRefGoogle Scholar
  44. Cohen S, Greenberg M E (2008). Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Annu Rev Cell Dev Biol, 24: 183–209PubMedCrossRefGoogle Scholar
  45. Collins A L, Levenson J M, Vilaythong A P, Richman R, Armstrong D L, Noebels J L, David Sweatt J, Zoghbi H Y (2004). Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet, 13(21): 2679–2689PubMedCrossRefGoogle Scholar
  46. Comery T A, Harris J B, Willems P J, Oostra B A, Irwin S A, Weiler I J, Greenough W T (1997). Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A, 94(10): 5401–5404PubMedCrossRefGoogle Scholar
  47. Day M, Wang Z, Ding J, An X, Ingham C A, Shering A F, Wokosin D, Ilijic E, Sun Z, Sampson A R, Mugnaini E, Deutch A Y, Sesack S R, Arbuthnott G W, Surmeier D J (2006). Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models. Nat Neurosci, 9(2): 251–259PubMedCrossRefGoogle Scholar
  48. De Carlos J A, Borrell J (2007). A historical reflection of the contributions of Cajal and Golgi to the foundations of neuroscience. Brain Res Rev, 55(1): 8–16PubMedCrossRefGoogle Scholar
  49. Detich N, Theberge J, Szyf M (2002). Promoter-specific activation and demethylation by MBD2/demethylase. J Biol Chem, 277(39): 35791–35794PubMedCrossRefGoogle Scholar
  50. Dillon C, Goda Y (2005). The actin cytoskeleton: integrating form and function at the synapse. Annu Rev Neurosci, 28: 25–55PubMedCrossRefGoogle Scholar
  51. Ding F, Li HH, Zhang S, Solomon NM, Camper SA, Cohen P, Francke U (2008). SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice. PLoS One, 3: e1709PubMedCrossRefGoogle Scholar
  52. Dockendorff T C, Su H S, McBride S M, Yang Z, Choi C H, Siwicki K K, Sehgal A, Jongens T A (2002). Drosophila lacking dfmr1 activity show defects in circadian output and fail to maintain courtship interest. Neuron, 34(6): 973–984PubMedCrossRefGoogle Scholar
  53. Duan X, Chang J H, Ge S, Faulkner R L, Kim J Y, Kitabatake Y, Liu X B, Yang C H, Jordan J D, Ma D K, Liu C Y, Ganesan S, Cheng H J, Ming G L, Lu B, Song H (2007). Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell, 130(6): 1146–1158PubMedCrossRefGoogle Scholar
  54. Edbauer D, Neilson J R, Foster K A, Wang C F, Seeburg D P, Batterton M N, Tada T, Dolan B M, Sharp P A, Sheng M (2010). Regulation of synaptic structure and function by FMRP-associated microRNAs miR-125b and miR-132. Neuron, 65(3): 373–384PubMedCrossRefGoogle Scholar
  55. Egger G, Liang G, Aparicio A, Jones P A (2004). Epigenetics in human disease and prospects for epigenetic therapy. Nature, 429(6990): 457–463PubMedCrossRefGoogle Scholar
  56. Elsea S H, Girirajan S (2008). Smith-Magenis syndrome. Eur J Hum Genet, 16(4): 412–421PubMedCrossRefGoogle Scholar
  57. Fan G, Beard C, Chen R Z, Csankovszki G, Sun Y, Siniaia M, Biniszkiewicz D, Bates B, Lee P P, Kuhn R, Trumpp A, Poon C, Wilson C B, Jaenisch R (2001). DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals. J Neurosci, 21(3): 788–797PubMedGoogle Scholar
  58. Feng J, Zhou Y, Campbell S L, Le T, Li E, Sweatt J D, Silva A J, Fan G (2010). Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons. Nat Neurosci, 13(4): 423–430PubMedCrossRefGoogle Scholar
  59. Ferrer I, Fabregues I, Coll J, Ribalta T, Rives A (1984). Tuberous sclerosis: a Golgi study of cortical tuber. Clin Neuropathol, 3(2): 47–51PubMedGoogle Scholar
  60. Ferrer I, Gullotta F (1990). Down’s syndrome and Alzheimer’s disease: dendritic spine counts in the hippocampus. Acta Neuropathol, 79(6): 680–685PubMedCrossRefGoogle Scholar
  61. Fiala J C, Feinberg M, Popov V, Harris K M (1998). Synaptogenesis via dendritic filopodia in developing hippocampal area CA1. J Neurosci, 18(21): 8900–8911PubMedGoogle Scholar
  62. Fiala J C, Spacek J, Harris KM (2002). Dendritic spine pathology: cause or consequence of neurological disorders? Brain Res Brain Res Rev, 39(1): 29–54PubMedCrossRefGoogle Scholar
  63. Filipowicz W, Bhattacharyya S N, Sonenberg N (2008). Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet, 9(2): 102–114PubMedCrossRefGoogle Scholar
  64. Fiore R, Siegel G, Schratt G (2008). MicroRNA function in neuronal development, plasticity and disease. Biochim Biophys Acta, 1779(8): 471–478PubMedGoogle Scholar
  65. Gage F H (2002). Neurogenesis in the adult brain. J Neurosci, 22(3): 612–613PubMedGoogle Scholar
  66. Galvez R, Gopal A R, Greenough W T (2003). Somatosensory cortical barrel dendritic abnormalities in a mouse model of the fragile X mental retardation syndrome. Brain Res, 971(1): 83–89PubMedCrossRefGoogle Scholar
  67. Gemelli T, Berton O, Nelson E D, Perrotti L I, Jaenisch R, Monteggia L M (2006). Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice. Biol Psychiatry, 59(5): 468–476PubMedCrossRefGoogle Scholar
  68. Golshani P, Hutnick L, Schweizer F, Fan G (2005). Conditional Dnmt1 deletion in dorsal forebrain disrupts development of somatosensory barrel cortex and thalamocortical long-term potentiation. Thalamus Relat Syst, 3(3): 227–233PubMedCrossRefGoogle Scholar
  69. Gothelf D, Feinstein C, Thompson T, Gu E, Penniman L, Van Stone E, Kwon H, Eliez S, Reiss A L (2007). Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome. Am J Psychiatry, 164(4): 663–669PubMedCrossRefGoogle Scholar
  70. Gräff J, Mansuy I M (2009). Epigenetic dysregulation in cognitive disorders. Eur J Neurosci, 30(1): 1–8PubMedCrossRefGoogle Scholar
  71. Greenough WT, Klintsova A Y, Irwin S A, Galvez R, Bates K E, Weiler I J (2001). Synaptic regulation of protein synthesis and the fragile X protein. Proc Natl Acad Sci U S A, 98(13): 7101–7106PubMedCrossRefGoogle Scholar
  72. Grewal S I, Elgin S C (2007). Transcription and RNA interference in the formation of heterochromatin. Nature, 447(7143): 399–406PubMedCrossRefGoogle Scholar
  73. Grossman AW, Aldridge GM, Weiler I J, Greenough WT (2006). Local protein synthesis and spine morphogenesis: Fragile X syndrome and beyond. J Neurosci, 26(27): 7151–7155PubMedCrossRefGoogle Scholar
  74. Grutzendler J, Kasthuri N, Gan W B (2002). Long-term dendritic spine stability in the adult cortex. Nature, 420(6917): 812–816PubMedCrossRefGoogle Scholar
  75. Guan J S, Haggarty S J, Giacometti E, Dannenberg J H, Joseph N, Gao J, Nieland T J, Zhou Y, Wang X, Mazitschek R, Bradner J E, DePinho R A, Jaenisch R, Tsai L H (2009). HDAC2 negatively regulates memory formation and synaptic plasticity. Nature, 459(7243): 55–60PubMedCrossRefGoogle Scholar
  76. Guy J, Hendrich B, Holmes M, Martin J E, Bird A (2001). A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet, 27(3): 322–326PubMedCrossRefGoogle Scholar
  77. Hagberg B, Aicardi J, Dias K, Ramos O (1983). A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann Neurol, 14(4): 471–479PubMedCrossRefGoogle Scholar
  78. Harris K M, Kater S B (1994). Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. Annu Rev Neurosci, 17: 341–371PubMedCrossRefGoogle Scholar
  79. Higashi Y, Murayama S, Pentchev P G, Suzuki K (1993). Cerebellar degeneration in the Niemann-Pick type C mouse. Acta Neuropathol, 85(2): 175–184PubMedCrossRefGoogle Scholar
  80. Hinton V J, Brown WT, Wisniewski K, Rudelli R D (1991). Analysis of neocortex in three males with the fragile X syndrome. Am J Med Genet, 41(3): 289–294PubMedCrossRefGoogle Scholar
  81. Holliday R, Pugh J E (1975). DNA modification mechanisms and gene activity during development. Science, 187(4173): 226–232PubMedCrossRefGoogle Scholar
  82. Hoogenraad C C, Koekkoek B, Akhmanova A, Krugers H, Dortland B, Miedema M, van Alphen A, Kistler WM, Jaegle M, Koutsourakis M, Van Camp N, Verhoye M, van der Linden A, Kaverina I, Grosveld F, De Zeeuw C I, Galjart N (2002). Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nat Genet, 32(1): 116–127PubMedCrossRefGoogle Scholar
  83. Hotta Y, Benzer S (1970). Genetic dissection of the Drosophila nervous system by means of mosaics. Proc Natl Acad Sci U S A, 67(3): 1156–1163PubMedCrossRefGoogle Scholar
  84. Hsieh J, Nakashima K, Kuwabara T, Mejia E, Gage F H (2004). Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc Natl Acad Sci U S A, 101(47): 16659–16664PubMedCrossRefGoogle Scholar
  85. Hull C, Hagerman R J (1993). A study of the physical, behavioral, and medical phenotype, including anthropometric measures, of females with fragile X syndrome. Am J Dis Child, 147(11): 1236–1241PubMedGoogle Scholar
  86. Hutnick L K, Golshani P, Namihira M, Xue Z, Matynia A, Yang X W, Silva A J, Schweizer F E, Fan G (2009). DNA hypomethylation restricted to the murine forebrain induces cortical degeneration and impairs postnatal neuronal maturation. Hum Mol Genet, 18(15): 2875–2888PubMedCrossRefGoogle Scholar
  87. Huttenlocher P R (1970). Dendritic development and mental defect. Neurology, 20(4): 381PubMedGoogle Scholar
  88. Huttenlocher P R (1974). Dendritic development in neocortex of children with mental defect and infantile spasms. Neurology, 24(3): 203–210PubMedGoogle Scholar
  89. Irwin S A, Patel B, Idupulapati M, Harris J B, Crisostomo R A, Larsen B P, Kooy F, Willems P J, Cras P, Kozlowski P B, Swain R A, Weiler I J, Greenough W T (2001). Abnormal dendritic spine characteristics in the temporal and visual cortices of patients with fragile-X syndrome: a quantitative examination. Am J Med Genet, 98(2): 161–167PubMedCrossRefGoogle Scholar
  90. Ishizuka A, Siomi M C, Siomi H (2002). A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev, 16(19): 2497–2508PubMedCrossRefGoogle Scholar
  91. Ivey K N, Muth A, Arnold J, King F W, Yeh R F, Fish J E, Hsiao E C, Schwartz R J, Conklin B R, Bernstein H S, Srivastava D (2008). MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell, 2(3): 219–229PubMedCrossRefGoogle Scholar
  92. Jaenisch R, Bird A (2003). Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet, 33(Suppl): 245–254PubMedCrossRefGoogle Scholar
  93. Jin P, Zarnescu D C, Ceman S, Nakamoto M, Mowrey J, Jongens T A, Nelson D L, Moses K, Warren S T (2004). Biochemical and genetic interaction between the fragile X mental retardation protein and the microRNA pathway. Nat Neurosci, 7(2): 113–117PubMedCrossRefGoogle Scholar
  94. Johansson B B, Belichenko P V (2002). Neuronal plasticity and dendritic spines: effect of environmental enrichment on intact and postischemic rat brain. J Cereb Blood Flow Metab, 22(1): 89–96PubMedCrossRefGoogle Scholar
  95. Johnston R J, Hobert O (2003). A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature, 426(6968): 845–849PubMedCrossRefGoogle Scholar
  96. Jones P A, Baylin S B (2002). The fundamental role of epigenetic events in cancer. Nat Rev Genet, 3(6): 415–428PubMedGoogle Scholar
  97. Jugloff D G, Jung B P, Purushotham D, Logan R, Eubanks J H (2005). Increased dendritic complexity and axonal length in cultured mouse cortical neurons overexpressing methyl-CpG-binding protein MeCP2. Neurobiol Dis, 19(1–2): 18–27PubMedCrossRefGoogle Scholar
  98. Kanellopoulou C, Muljo S A, Kung A L, Ganesan S, Drapkin R, Jenuwein T, Livingston D M, Rajewsky K (2005). Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev, 19(4): 489–501PubMedCrossRefGoogle Scholar
  99. Kaufmann W E, Moser H W (2000). Dendritic anomalies in disorders associated with mental retardation. Cereb Cortex, 10(10): 981–991PubMedCrossRefGoogle Scholar
  100. Kishi N, Macklis J D (2004). MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci, 27(3): 306–321PubMedGoogle Scholar
  101. Klose R J, Bird A P (2006). Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci, 31(2): 89–97PubMedCrossRefGoogle Scholar
  102. Kobrynski L J, Sullivan K E (2007). Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet, 370(9596): 1443–1452PubMedCrossRefGoogle Scholar
  103. Kooy R F (2003). Of mice and the fragile X syndrome. Trends Genet, 19(3): 148–154PubMedCrossRefGoogle Scholar
  104. Kooy R F, D’Hooge R, Reyniers E, Bakker C E, Nagels G, De Boulle K, Storm K, Clincke G, De Deyn P P, Oostra B A, Willems P J (1996). Transgenic mouse model for the fragile X syndrome. Am J Med Genet, 64(2): 241–245PubMedCrossRefGoogle Scholar
  105. Krichevsky A M, Sonntag K C, Isacson O, Kosik K S (2006). Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells, 24(4): 857–864PubMedCrossRefGoogle Scholar
  106. Krogan N J, Kim M, Tong A, Golshani A, Cagney G, Canadien V, Richards D P, Beattie B K, Emili A, Boone C, Shilatifard A, Buratowski S, Greenblatt J (2003). Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol, 23(12): 4207–4218PubMedCrossRefGoogle Scholar
  107. Lachner M, O’sullivan R J, Jenuwein T (2003). An epigenetic road map for histone lysine methylation. J Cell Sci, 116(Pt 11): 2117–2124PubMedCrossRefGoogle Scholar
  108. Lalande M, Calciano M A (2007). Molecular epigenetics of Angelman syndrome. Cell Mol Life Sci, 64(7–8): 947–960PubMedCrossRefGoogle Scholar
  109. Lee J A, Lupski J R (2006). Genomic rearrangements and gene copynumber alterations as a cause of nervous system disorders. Neuron, 52(1): 103–121PubMedCrossRefGoogle Scholar
  110. Lee T I, Jenner R G, Boyer L A, Guenther MG, Levine S S, Kumar RM, Chevalier B, Johnstone S E, Cole M F, Isono K, Koseki H, Fuchikami T, Abe K, Murray H L, Zucker J P, Yuan B, Bell G W, Herbolsheimer E, Hannett N M, Sun K, Odom D T, Otte A P, Volkert T L, Bartel D P, Melton D A, Gifford D K, Jaenisch R, Young R A (2006). Control of developmental regulators by Polycomb in human embryonic stem cells. Cell, 125(2): 301–313PubMedCrossRefGoogle Scholar
  111. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim V N (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature, 425(6956): 415–419PubMedCrossRefGoogle Scholar
  112. Leucht C, Stigloher C, Wizenmann A, Klafke R, Folchert A, Bally-Cuif L (2008). MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. Nat Neurosci, 11(6): 641–648PubMedCrossRefGoogle Scholar
  113. Lewis D A, Glantz L A, Pierri J N, Sweet R A (2003). Altered cortical glutamate neurotransmission in schizophrenia: evidence from morphological studies of pyramidal neurons. Ann N Y Acad Sci, 1003: 102–112PubMedCrossRefGoogle Scholar
  114. Li X, Zhao X (2008). Epigenetic regulation of mammalian stem cells. Stem Cells Dev, 17(6): 1043–1052PubMedCrossRefGoogle Scholar
  115. Lim MK, Kawamura T, Ohsawa Y, Ohtsubo M, Asakawa S, Takayanagi A, Shimizu N (2007). Parkin interacts with LIM Kinase 1 and reduces its cofilin-phosphorylation activity via ubiquitination. Exp Cell Res, 313(13): 2858–2874PubMedCrossRefGoogle Scholar
  116. Lin Y J, Seroude L, Benzer S (1998). Extended life-span and stress resistance in the Drosophila mutant methuselah. Science, 282(5390): 943–946PubMedCrossRefGoogle Scholar
  117. Ling S C, Fahrner P S, Greenough WT, Gelfand V I (2004). Transport of Drosophila fragile X mental retardation protein-containing ribonucleoprotein granules by kinesin-1 and cytoplasmic dynein. Proc Natl Acad Sci U S A, 101(50): 17428–17433PubMedCrossRefGoogle Scholar
  118. Liu C, Teng Z Q, Santistevan N J, Szulwach K E, Guo W, Jin P, Zhao X (2010). Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell, 6(5): 433–444PubMedCrossRefGoogle Scholar
  119. Liu C, Zhao X (2009). MicroRNAs in adult and embryonic neurogenesis. Neuromolecular Med, 11(3): 141–152PubMedCrossRefGoogle Scholar
  120. Logue S F, Paylor R, Wehner J M (1997). Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task. Behav Neurosci, 111(1): 104–113PubMedCrossRefGoogle Scholar
  121. Lugli G, Torvik V I, Larson J, Smalheiser N R (2008). Expression of microRNAs and their precursors in synaptic fractions of adult mouse forebrain. J Neurochem, 106(2): 650–661PubMedCrossRefGoogle Scholar
  122. Luikenhuis S, Giacometti E, Beard C F, Jaenisch R (2004). Expression of MeCP2 in postmitotic neurons rescues Rett syndrome in mice. Proc Natl Acad Sci U S A, 101(16): 6033–6038PubMedCrossRefGoogle Scholar
  123. Luo Y, Shan G, Guo W, Smrt R D, Johnson E B, Li X, Pfeiffer R L, Szulwach K E, Duan R, Barkho B Z, Li W, Liu C, Jin P, Zhao X (2010). Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells. PLoS Genet, 6(4): e1000898PubMedCrossRefGoogle Scholar
  124. Lush MJ, Li Y, Read D J, Willis A C, Glynn P (1998). Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. Biochem J, 332(Pt 1): 1–4PubMedGoogle Scholar
  125. Ma D K, Jang M H, Guo J U, Kitabatake Y, Chang M L, Pow-Anpongkul N, Flavell R A, Lu B, Ming G L, Song H (2009). Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science, 323(5917): 1074–1077PubMedCrossRefGoogle Scholar
  126. Machado-Salas J P (1984). Abnormal dendritic patterns and aberrant spine development in Bourneville’s disease—a Golgi survey. Clin Neuropathol, 3(2): 52–58PubMedGoogle Scholar
  127. Marin-Padilla M (1972). Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study. Brain Res, 44(2): 625–629PubMedCrossRefGoogle Scholar
  128. Marin-Padilla M (1976). Pyramidal cell abnormalities in the motor cortex of a child with Down’s syndrome. A Golgi study. J Comp Neurol, 167(1): 63–81PubMedCrossRefGoogle Scholar
  129. Marsh J L, Thompson L M (2006). Drosophila in the study of neurodegenerative disease. Neuron, 52(1): 169–178PubMedCrossRefGoogle Scholar
  130. Matarazzo V, Cohen D, Palmer A M, Simpson P J, Khokhar B, Pan S J, Ronnett G V (2004). The transcriptional repressor Mecp2 regulates terminal neuronal differentiation. Mol Cell Neurosci, 27(1): 44–58PubMedCrossRefGoogle Scholar
  131. Meng Y, Zhang Y, Tregoubov V, Janus C, Cruz L, Jackson M, Lu W Y, MacDonald J F, Wang J Y, Falls D L, Jia Z (2002). Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron, 35(1): 121–133PubMedCrossRefGoogle Scholar
  132. Michel C I, Kraft R, Restifo L L (2004). Defective neuronal development in the mushroom bodies of Drosophila fragile X mental retardation 1 mutants. J Neurosci, 24(25): 5798–5809PubMedCrossRefGoogle Scholar
  133. Min K T, Benzer S (1999). Preventing neurodegeneration in the Drosophila mutant bubblegum. Science, 284(5422): 1985–1988PubMedCrossRefGoogle Scholar
  134. Mineur Y S, Sluyter F, de Wit S, Oostra B A, Crusio W E (2002). Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse. Hippocampus, 12(1): 39–46PubMedCrossRefGoogle Scholar
  135. Miura K, Kishino T, Li E, Webber H, Dikkes P, Holmes G L, Wagstaff J (2002). Neurobehavioral and electroencephalographic abnormalities in Ube3a maternal-deficient mice. Neurobiol Dis, 9(2): 149–159PubMedCrossRefGoogle Scholar
  136. Morales J, Hiesinger P R, Schroeder A J, Kume K, Verstreken P, Jackson F R, Nelson D L, Hassan B A (2002). Drosophila fragile X protein, DFXR, regulates neuronal morphology and function in the brain. Neuron, 34(6): 961–972PubMedCrossRefGoogle Scholar
  137. Moretti P, Levenson JM, Battaglia F, Atkinson R, Teague R, Antalffy B, Armstrong D, Arancio O, Sweatt J D, Zoghbi H Y (2006). Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J Neurosci, 26(1): 319–327PubMedCrossRefGoogle Scholar
  138. Morris R G, Garrud P, Rawlins J N, O’Keefe J (1982). Place navigation impaired in rats with hippocampal lesions. Nature, 297(5868): 681–683PubMedCrossRefGoogle Scholar
  139. Nimchinsky E A, Oberlander A M, Svoboda K (2001). Abnormal development of dendritic spines in FMR1 knock-out mice. J Neurosci, 21(14): 5139–5146PubMedGoogle Scholar
  140. Nishino J, Kim I, Chada K, Morrison S J (2008). Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf Expression. Cell, 135(2): 227–239PubMedCrossRefGoogle Scholar
  141. Nomura T, Kimura M, Horii T, Morita S, Soejima H, Kudo S, Hatada I (2008). MeCP2-dependent repression of an imprinted miR-184 released by depolarization. Hum Mol Genet, 17(8): 1192–1199PubMedCrossRefGoogle Scholar
  142. O’Carroll D, Erhardt S, Pagani M, Barton S C, Surani M A, Jenuwein T (2001). The polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol, 21(13): 4330–4336PubMedCrossRefGoogle Scholar
  143. Oberle I, Rousseau F, Heitz D, Kretz C, Devys D, Hanauer A, Boue J, Bertheas M, Mandel J (1991). Instability of a 550-base pair DNA segment and abnormal methylation in fragile X syndrome. Science, 252: 1097–1102CrossRefGoogle Scholar
  144. Ostroff L E, Fiala J C, Allwardt B, Harris K M (2002). Polyribosomes redistribute from dendritic shafts into spines with enlarged synapses during LTP in developing rat hippocampal slices. Neuron, 35(3): 535–545PubMedCrossRefGoogle Scholar
  145. Papazian D M, Schwarz T L, Tempel B L, Jan Y N, Jan L Y (1987). Cloning of genomic and complementary DNA from Shaker, a putative potassium channel gene from Drosophila. Science, 237(4816): 749–753PubMedCrossRefGoogle Scholar
  146. Parrish J Z, Emoto K, Jan L Y, Jan Y N (2007a). Polycomb genes interact with the tumor suppressor genes hippo and warts in the maintenance of Drosophila sensory neuron dendrites. Genes Dev, 21(8): 956–972PubMedCrossRefGoogle Scholar
  147. Parrish J Z, Emoto K, Kim M D, Jan Y N (2007b). Mechanisms that regulate establishment, maintenance, and remodeling of dendritic fields. Annu Rev Neurosci, 30: 399–423PubMedCrossRefGoogle Scholar
  148. Penagarikano O, Mulle J G, Warren S T (2007). The pathophysiology of fragile x syndrome. Annu Rev Genomics Hum Genet, 8: 109–129PubMedCrossRefGoogle Scholar
  149. Persico A M, Bourgeron T (2006). Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci, 29(7): 349–358PubMedCrossRefGoogle Scholar
  150. Phiel C J, Zhang F, Huang E Y, Guenther M G, Lazar M A, Klein P S (2001). Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem, 276(39): 36734–36741PubMedCrossRefGoogle Scholar
  151. Pittenger C, Duman R S (2008). Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology, 33(1): 88–109PubMedCrossRefGoogle Scholar
  152. Potocki L, Bi W, Treadwell-Deering D, Carvalho C M, Eifert A, Friedman E M, Glaze D, Krull K, Lee J A, Lewis R A, Mendoza-Londono R, Robbins-Furman P, Shaw C, Shi X, Weissenberger G, Withers M, Yatsenko S A, Zackai E H, Stankiewicz P, Lupski J R (2007). Characterization of Potocki-Lupski syndrome (dup(17) (p11.2p11.2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet, 80(4): 633–649PubMedCrossRefGoogle Scholar
  153. Poy M N, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald P E, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M (2004). A pancreatic islet-specific microRNA regulates insulin secretion. Nature, 432(7014): 226–230PubMedCrossRefGoogle Scholar
  154. Purpura D P (1974). Dendritic spine “dysgenesis” and mental retardation. Science, 186(4169): 1126–112PubMedCrossRefGoogle Scholar
  155. Purpura D P (1975). Dendritic differentiation in human cerebral cortex: normal and aberrant developmental patterns. Adv Neurol, 12: 91–134PubMedGoogle Scholar
  156. Rajasethupathy P, Fiumara F, Sheridan R, Betel D, Puthanveettil S V, Russo J J, Sander C, Tuschl T, Kandel E (2009). Characterization of small RNAs in aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron, 63(6): 803–817PubMedCrossRefGoogle Scholar
  157. Ramocki M B, Zoghbi H Y (2008). Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature, 455(7215): 912–918PubMedCrossRefGoogle Scholar
  158. Redmond L, Kashani A H, Ghosh A (2002). Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription. Neuron, 34(6): 999–1010PubMedCrossRefGoogle Scholar
  159. Reiter L T, Potocki L, Chien S, Gribskov M, Bier E (2001). A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res, 11(6): 1114–1125PubMedCrossRefGoogle Scholar
  160. Riggs A D (1975). X inactivation, differentiation, and DNA methylation. Cytogenet Cell Genet, 14(1): 9–25PubMedCrossRefGoogle Scholar
  161. Robertson K D, Ait-Si-Ali S, Yokochi T, Wade P A, Jones P L, Wolffe A P (2000). DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet, 25(3): 338–342PubMedCrossRefGoogle Scholar
  162. Robinson T E, Kolb B (2004). Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology, 47(Suppl 1): 33–46PubMedCrossRefGoogle Scholar
  163. Rosenthal N, Brown S (2007). The mouse ascending: perspectives for human-disease models. Nat Cell Biol, 9(9): 993–999PubMedCrossRefGoogle Scholar
  164. Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl E E, Nitsch R, Wulczyn F G (2008). A feedback loop comprising lin-28 and let-7 controls prelet-7 maturation during neural stem-cell commitment. Nat Cell Biol, 10(8): 987–993PubMedCrossRefGoogle Scholar
  165. Sahoo T, del Gaudio D, German J R, Shinawi M, Peters S U, Person R E, Garnica A, Cheung S W, Beaudet A L (2008). Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nat Genet, 40(6): 719–721PubMedCrossRefGoogle Scholar
  166. Santos-Rosa H, Schneider R, Bannister A J, Sherriff J, Bernstein B E, Emre N C, Schreiber S L, Mellor J, Kouzarides T (2002). Active genes are tri-methylated at K4 of histone H3. Nature, 419(6905): 407–411PubMedCrossRefGoogle Scholar
  167. Sarna J R, Larouche M, Marzban H, Sillitoe R V, Rancourt D E, Hawkes R (2003). Patterned Purkinje cell degeneration in mouse models of Niemann-Pick type C disease. J Comp Neurol, 456(3): 279–291PubMedCrossRefGoogle Scholar
  168. Schratt G (2009). microRNAs at the synapse. Nat Rev Neurosci, 10(12): 842–849PubMedCrossRefGoogle Scholar
  169. Schratt G M, Tuebing F, Nigh E A, Kane C G, Sabatini M E, Kiebler M, Greenberg M E (2006). A brain-specific microRNA regulates dendritic spine development. Nature, 439(7074): 283–289PubMedCrossRefGoogle Scholar
  170. Schübeler D, MacAlpine D M, Scalzo D, Wirbelauer C, Kooperberg C, van Leeuwen F, Gottschling D E, O’Neill L P, Turner BM, Delrow J, Bell S P, Groudine M (2004). The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. Genes Dev, 18(11): 1263–1271PubMedCrossRefGoogle Scholar
  171. Schwamborn J C, Berezikov E, Knoblich J A (2009). The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell, 136(5): 913–925PubMedCrossRefGoogle Scholar
  172. Segal M (2005). Dendritic spines and long-term plasticity. Nat Rev Neurosci, 6(4): 277–284PubMedCrossRefGoogle Scholar
  173. Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H (2002). Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron, 35(2): 243–254PubMedCrossRefGoogle Scholar
  174. Shahbazian M D, Zoghbi H Y (2002). Rett syndrome and MeCP2: linking epigenetics and neuronal function. Am J Hum Genet, 71(6): 1259–1272PubMedCrossRefGoogle Scholar
  175. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu R T, Gage F H, Evans R M (2004). Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature, 427(6969): 78–83PubMedCrossRefGoogle Scholar
  176. Siegel G, Obernosterer G, Fiore R, Oehmen M, Bicker S, Christensen M, Khudayberdiev S, Leuschner P F, Busch C J, Kane C, Hübel K, Dekker F, Hedberg C, Rengarajan B, Drepper C, Waldmann H, Kauppinen S, Greenberg M E, Draguhn A, Rehmsmeier M, Martinez J, Schratt G M (2009). A functional screen implicates microRNA-138-dependent regulation of the depalmitoylation enzyme APT1 in dendritic spine morphogenesis. Nat Cell Biol, 11(6): 705–716PubMedCrossRefGoogle Scholar
  177. Slager R E, Newton T L, Vlangos C N, Finucane B, Elsea S H (2003). Mutations in RAI1 associated with Smith-Magenis syndrome. Nat Genet, 33(4): 466–468PubMedCrossRefGoogle Scholar
  178. Slegtenhorst-Eegdeman K E, de Rooij D G, Verhoef-Post M, van de Kant H J, Bakker C E, Oostra B A, Grootegoed J A, Themmen A P (1998). Macroorchidism in FMR1 knockout mice is caused by increased Sertoli cell proliferation during testicular development. Endocrinology, 139(1): 156–162PubMedCrossRefGoogle Scholar
  179. Smrt R D, Eaves-Egenes J, Barkho B Z, Santistevan N J, Zhao C, Aimone J B, Gage F H, Zhao X (2007). Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol Dis, 27(1): 77–89PubMedCrossRefGoogle Scholar
  180. Smrt R D, Szulwach K E, Pfeiffer R L, Li X, Guo W, Pathania M, Teng Z Q, Luo Y, Peng J, Bordey A, Jin P, Zhao X (2010). MicroRNA miR-137 regulates neuronal maturation by targeting ubiquitin ligase mind bomb-1. Stem Cells, 28(6): 1060–1070PubMedCrossRefGoogle Scholar
  181. Snow W M, Hartle K, Ivanco T L (2008). Altered morphology of motor cortex neurons in the VPA rat model of autism. Dev Psychobiol, 50(7): 633–639PubMedCrossRefGoogle Scholar
  182. Song H, Kempermann G, Overstreet Wadiche L, Zhao C, Schinder A F, Bischofberger J (2005). New neurons in the adult mammalian brain: synaptogenesis and functional integration. J Neurosci, 25(45): 10366–10368PubMedCrossRefGoogle Scholar
  183. Spires T L, Grote H E, Garry S, Cordery P M, Van Dellen A, Blakemore C, Hannan A J (2004). Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington’s disease transgenic mice. Eur J Neurosci, 19(10): 2799–2807PubMedCrossRefGoogle Scholar
  184. Stark K L, Xu B, Bagchi A, Lai W S, Liu H, Hsu R, Wan X, Pavlidis P, Mills A A, Karayiorgou M, Gogos J A (2008). Altered brain microRNA biogenesis contributes to phenotypic deficits in a 22q11-deletion mouse model. Nat Genet, 40(6): 751–760PubMedCrossRefGoogle Scholar
  185. Suetsugu M, Mehraein P (1980). Spine distribution along the apical dendrites of the pyramidal neurons in Down’s syndrome. A quantitative Golgi study. Acta Neuropathol, 50(3): 207–210PubMedCrossRefGoogle Scholar
  186. Sutton M A, Schuman E M (2005). Local translational control in dendrites and its role in long-term synaptic plasticity. J Neurobiol, 64(1): 116–131PubMedCrossRefGoogle Scholar
  187. Suzuki T, Tian Q B, Kuromitsu J, Kawai T, Endo S (2007). Characterization of mRNA species that are associated with postsynaptic density fraction by gene chip microarray analysis. Neurosci Res, 57(1): 61–85PubMedCrossRefGoogle Scholar
  188. Szulwach K E, Li X, Smrt R D, Li Y, Luo Y, Lin L, Santistevan N J, Li W, Zhao X, Jin P (2010). Cross talk between microRNA and epigenetic regulation in adult neurogenesis. J Cell Biol, 189(1): 127–141PubMedCrossRefGoogle Scholar
  189. Takai D, Jones P A (2002). Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A, 99(6): 3740–3745PubMedCrossRefGoogle Scholar
  190. Takashima S, Becker L E, Armstrong D L, Chan F (1981). Abnormal neuronal development in the visual cortex of the human fetus and infant with down’s syndrome. A quantitative and qualitative Golgi study. Brain Res, 225(1): 1–21PubMedCrossRefGoogle Scholar
  191. Takashima S, Iida K, Mito T, Arima M (1994). Dendritic and histochemical development and ageing in patients with Down’s syndrome. J Intellect Disabil Res, 38(Pt 3): 265–273PubMedGoogle Scholar
  192. Toni N, Laplagne D A, Zhao C, Lombardi G, Ribak C E, Gage F H, Schinder A F (2008). Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci, 11(8): 901–907PubMedCrossRefGoogle Scholar
  193. Tudor M, Akbarian S, Chen R Z, Jaenisch R (2002). Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain. Proc Natl Acad Sci U S A, 99(24): 15536–15541PubMedCrossRefGoogle Scholar
  194. Van de Bor V, Davis I (2004). mRNA localisation gets more complex. Curr Opin Cell Biol, 16(3): 300–307PubMedCrossRefGoogle Scholar
  195. van Praag H, Schinder A F, Christie B R, Toni N, Palmer T D, Gage F H (2002). Functional neurogenesis in the adult hippocampus. Nature, 415(6875): 1030–1034PubMedCrossRefGoogle Scholar
  196. Vanderklish P W, Edelman G M (2005). Differential translation and fragile X syndrome. Genes Brain Behav, 4(6): 360–384PubMedCrossRefGoogle Scholar
  197. Walkley S U, Baker H J (1984). Sphingomyelin lipidosis in a cat: Golgi studies. Acta Neuropathol, 65(2): 138–144PubMedCrossRefGoogle Scholar
  198. Wan L, Dockendorff T C, Jongens T A, Dreyfuss G (2000). Characterization of dFMR1, a Drosophila melanogaster homolog of the fragile X mental retardation protein. Mol Cell Biol, 20(22): 8536–8547PubMedCrossRefGoogle Scholar
  199. Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R (2007). DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet, 39(3): 380–385PubMedCrossRefGoogle Scholar
  200. Wayman G A, Davare M, Ando H, Fortin D, Varlamova O, Cheng H Y, Marks D, Obrietan K, Soderling T R, Goodman R H, Impey S (2008). An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP. Proc Natl Acad Sci U S A, 105(26): 9093–9098PubMedCrossRefGoogle Scholar
  201. Wayman G A, Impey S, Marks D, Saneyoshi T, Grant W F, Derkach V, Soderling T R (2006). Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron, 50(6): 897–909PubMedCrossRefGoogle Scholar
  202. Wisniewski K E, Segan S M, Miezejeski C M, Sersen E A, Rudelli R D (1991). The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities. Am J Med Genet, 38(2–3): 476–480PubMedCrossRefGoogle Scholar
  203. Xu X L, Li Y, Wang F, Gao F B (2008). The steady-state level of the nervous-system-specific microRNA-124a is regulated by dFMR1 in Drosophila. J Neurosci, 28(46): 11883–11889PubMedCrossRefGoogle Scholar
  204. Yamauchi J, Miyamoto Y, Kusakawa S, Torii T, Mizutani R, Sanbe A, Nakajima H, Kiyokawa N, Tanoue A (2008). Neurofibromatosis 2 tumor suppressor, the gene induced by valproic acid, mediates neurite outgrowth through interaction with paxillin. Exp Cell Res, 314(11–12): 2279–2288PubMedCrossRefGoogle Scholar
  205. Yamauchi J, Miyamoto Y, Torii T, Mizutani R, Nakamura K, Sanbe A, Koide H, Kusakawa S, Tanoue A (2009). Valproic acid-inducible Arl4D and cytohesin-2/ARNO, acting through the downstream Arf6, regulate neurite outgrowth in N1E-115 cells. Exp Cell Res, 315(12): 2043–2052PubMedCrossRefGoogle Scholar
  206. Yang L, Duan R, Chen D, Wang J, Chen D, Jin P (2007). Fragile X mental retardation protein modulates the fate of germline stem cells in Drosophila. Hum Mol Genet, 16(15): 1814–1820PubMedCrossRefGoogle Scholar
  207. Yoder J A, Walsh C P, Bestor T H (1997). Cytosine methylation and the ecology of intragenomic parasites. Trends Genet, 13(8): 335–340PubMedCrossRefGoogle Scholar
  208. Yoo A S, Staahl B T, Chen L, Crabtree G R (2009). MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature, 460(7255): 642–646PubMedGoogle Scholar
  209. Zhang Y Q, Bailey A M, Matthies H J, Renden R B, Smith M A, Speese S D, Rubin G M, Broadie K (2001). Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function. Cell, 107(5): 591–603PubMedCrossRefGoogle Scholar
  210. Zhao C, Avilés C, Abel R A, Almli C R, McQuillen P, Pleasure S J (2005). Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Development, 132(12): 2917–2927PubMedCrossRefGoogle Scholar
  211. Zhao C, Sun G, Li S, Lang MF, Yang S, Li W, Shi Y (2010). MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling. Proc Natl Acad Sci U S A, 107(5): 1876–1881PubMedCrossRefGoogle Scholar
  212. Zhao C, Sun G, Li S, Shi Y (2009). A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. Nat Struct Mol Biol, 16(4): 365–371PubMedCrossRefGoogle Scholar
  213. Zhao C, Teng E M, Summers R G Jr, Ming G L, Gage F H (2006). Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci, 26(1): 3–11PubMedCrossRefGoogle Scholar
  214. Zhou Z, Hong E J, Cohen S, Zhao WN, Ho H Y, Schmidt L, Chen WG, Lin Y, Savner E, Griffith E C, Hu L, Steen J A, Weitz C J, Greenberg M E (2006). Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron, 52(2): 255–269PubMedCrossRefGoogle Scholar
  215. Zoghbi H Y (2003). Postnatal neurodevelopmental disorders: meeting at the synapse? Science, 302(5646): 826–830PubMedCrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  1. 1.Department of NeuroscienceUniversity of New Mexico School of MedicineAlbuquerqueUSA

Personalised recommendations