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Generation of neuronal variability and complexity

Nature volume 441, pages 1087–1093 (2006)Cite this article

Abstract

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The production of specialized differentiated neurons derived from stem cells has been proposed as a revolutionary technology for regenerative medicine. However, few examples of specific neuronal cell differentiation have been described so far. Although stem-cell tissue replacement might be seemingly straightforward in other cases, the high degree of complexity of the nervous system raises the challenge of tissue replacement substantially. Understanding mechanisms of neuronal diversification will not only be relevant for therapeutic purposes but might also shed light on the differences in cognitive abilities, personality traits and psychiatric conditions observed in humans.

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Figure 1: Generation of somatic variability in the immune and neural systems.
Figure 2: Aneuploidy as a mechanism to alter gene expression in the CNS.
Figure 3: A model for generation of neuronal diversity by L1 retrotransposition.
Figure 4: Alternative start sites.
Figure 5: Alternative poly(A) sites.

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References

  1. Koch, C. & Laurent, G. Complexity and the nervous system. Science 284, 96–98 (1999).

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Vogel, E. K. & Machizawa, M. G. Neural activity predicts individual differences in visual working memory capacity. Nature 428, 748–751 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Williams, R. W. Mapping genes that modulate mouse brain development: a quantitative genetic approach. Results Probl. Cell Differ. 30, 21–49 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Pakkenberg, B. et al. Aging and the human neocortex. Exp. Gerontol. 38, 95–99 (2003).

    Article  PubMed  Google Scholar 

  5. Angevine, J. B. Jr. Time of neuron origin in the diencephalon of the mouse. An autoradiographic study. J. Comp. Neurol. 139, 129–187 (1970).

    Article  PubMed  Google Scholar 

  6. Finlay, B. L. & Slattery, M. Local differences in the amount of early cell death in neocortex predict adult local specializations. Science 219, 1349–1351 (1983).

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Ferrer, I., Soriano, E., del Rio, J. A., Alcantara, S. & Auladell, C. Cell death and removal in the cerebral cortex during development. Prog. Neurobiol. 39, 1–43 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. Oppenheim, R. W. Cell death during development of the nervous system. Annu. Rev. Neurosci. 14, 453–501 (1991).

    Article  CAS  PubMed  Google Scholar 

  9. Lie, D. C., Song, H., Colamarino, S. A., Ming, G. L. & Gage, F. H. Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu. Rev. Pharmacol. Toxicol. 44, 399–421 (2004).

    Article  CAS  PubMed  Google Scholar 

  10. Taupin, P. & Gage, F. H. Adult neurogenesis and neural stem cells of the central nervous system in mammals. J. Neurosci. Res. 69, 745–749 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Gage, F. H. Mammalian neural stem cells. Science 287, 1433–1438 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  12. Jones, J. M. & Gellert, M. The taming of a transposon: V(D)J recombination and the immune system. Immunol. Rev. 200, 233–248 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. Gotz, M. & Sommer, L. Cortical development: the art of generating cell diversity. Development 132, 3327–3332 (2005).

    Article  PubMed  CAS  Google Scholar 

  14. Burgess, N. & O'Keefe, J. Neural representations in human spatial memory. Trends Cogn. Sci. 7, 517–519 (2003).

    Article  PubMed  Google Scholar 

  15. Gao, Y. et al. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell 95, 891–902 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Matsuoka, M. et al. Detection of somatic DNA recombination in the transgenic mouse brain. Science 254, 81–86 (1991).

    Article  ADS  CAS  PubMed  Google Scholar 

  17. Abeliovich, A. et al. On somatic recombination in the central nervous system of transgenic mice. Science 257, 404–410 (1992).

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Eggan, K. et al. Mice cloned from olfactory sensory neurons. Nature 428, 44–49 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Li, J., Ishii, T., Feinstein, P. & Mombaerts, P. Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons. Nature 428, 393–399 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Ogasawara, M., Aoki, K., Okada, S. & Suzumori, K. Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertil. Steril. 73, 300–304 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Pathak, S. & Multani, A. S. Aneuploidy, stem cells and cancer. EXS 2006, 49–64 (2006).

    Google Scholar 

  22. Palmer, T. D., Takahashi, J. & Gage, F. H. The adult rat hippocampus contains primordial neural stem cells. Mol. Cell. Neurosci. 8, 389–404 (1997).

    Article  CAS  PubMed  Google Scholar 

  23. Rehen, S. K. et al. Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc. Natl Acad. Sci. USA 98, 13361–13366 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rehen, S. K. et al. Constitutional aneuploidy in the normal human brain. J. Neurosci. 25, 2176–2180 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fuller, C. E. & Perry, A. Fluorescence in situ hybridization (FISH) in diagnostic and investigative neuropathology. Brain Pathol. 12, 67–86 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Kingsbury, M. A. et al. Aneuploid neurons are functionally active and integrated into brain circuitry. Proc. Natl Acad. Sci. USA 102, 6143–6147 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gaudet, J. & Mango, S. E. Regulation of organogenesis by the Caenorhabditis elegans FoxA protein PHA-4. Science 295, 821–825 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Yang, A. H. et al. Chromosome segregation defects contribute to aneuploidy in normal neural progenitor cells. J. Neurosci. 23, 10454–10462 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Muotri, A. R. et al. Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition. Nature 435, 903–910 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  30. Lander, E. S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Gibbs, R. A. et al. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 428, 493–521 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Waterston, R. H. et al. Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Wei, W. et al. Human L1 retrotransposition: cis preference versus trans complementation. Mol. Cell. Biol. 21, 1429–1439 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Esnault, C., Maestre, J. & Heidmann, T. Human LINE retrotransposons generate processed pseudogenes. Nature Genet. 24, 363–367 (2000).

    Article  CAS  PubMed  Google Scholar 

  35. Dewannieux, M., Esnault, C. & Heidmann, T. LINE-mediated retrotransposition of marked Alu sequences. Nature Genet. 35, 41–48 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Kajikawa, M. & Okada, N. LINEs mobilize SINEs in the eel through a shared 3′ sequence. Cell 111, 433–444 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Gilbert, N., Lutz, S., Morrish, T. A. & Moran, J. V. Multiple fates of L1 retrotransposition intermediates in cultured human cells. Mol. Cell. Biol. 25, 7780–7795 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kazazian, H. H. Jr. Mobile elements: drivers of genome evolution. Science 303, 1626–1632 (2004).

    Article  ADS  CAS  PubMed  Google Scholar 

  39. Smale, S. T. & Kadonaga, J. T. The RNA polymerase II core promoter. Annu. Rev. Biochem. 72, 449–479 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Ayoubi, T. A. & Van De Ven, W. J. Regulation of gene expression by alternative promoters. FASEB J. 10, 453–460 (1996).

    Article  CAS  PubMed  Google Scholar 

  41. Myers, S. J., Dingledine, R. & Borges, K. Genetic regulation of glutamate receptor ion channels. Annu. Rev. Pharmacol. Toxicol. 39, 221–241 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Tabuchi, A. et al. Differential activation of brain-derived neurotrophic factor gene promoters I and III by Ca2+ signals evoked via L-type voltage-dependent and N-methyl-D-aspartate receptor Ca2+ channels. J. Biol. Chem. 275, 17269–17275 (2000).

    Article  CAS  PubMed  Google Scholar 

  43. Liu, Q. R. et al. Rodent BDNF genes, novel promoters, novel splice variants, and regulation by cocaine. Brain Res. 1067, 1–12 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  44. Metsis, M., Timmusk, T., Arenas, E. & Persson, H. Differential usage of multiple brain-derived neurotrophic factor promoters in the rat brain following neuronal activation. Proc. Natl Acad. Sci. USA 90, 8802–8806 (1993).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  45. Maniatis, T. & Tasic, B. Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 418, 236–243 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Yeo, G., Holste, D., Kreiman, G. & Burge, C. B. Variation in alternative splicing across human tissues. Genome Biol. 5, R74 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Grabowski, P. J. & Black, D. L. Alternative RNA splicing in the nervous system. Prog. Neurobiol. 65, 289–308 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Dredge, B. K., Polydorides, A. D. & Darnell, R. B. The splice of life: alternative splicing and neurological disease. Nature Rev. Neurosci. 2, 43–50 (2001).

    Article  CAS  Google Scholar 

  49. Schmucker, D. et al. Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell 101, 671–684 (2000).

    Article  CAS  PubMed  Google Scholar 

  50. Missler, M. & Sudhof, T. C. Neurexins: three genes and 1001 products. Trends Genet. 14, 20–26 (1998).

    Article  CAS  PubMed  Google Scholar 

  51. Wu, Q. & Maniatis, T. A striking organization of a large family of human neural cadherin-like cell adhesion genes. Cell 97, 779–790 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Tasic, B. et al. Promoter choice determines splice site selection in protocadherin α and γ pre-mRNA splicing. Mol. Cell 10, 21–33 (2002).

    Article  CAS  PubMed  Google Scholar 

  53. Daoud, R., Da Penha Berzaghi, M., Siedler, F., Hubener, M. & Stamm, S. Activity-dependent regulation of alternative splicing patterns in the rat brain. Eur. J. Neurosci. 11, 788–802 (1999).

    Article  CAS  PubMed  Google Scholar 

  54. Vezzani, A., Speciale, C., Della Vedova, F., Tamburin, M. & Benatti, L. Alternative splicing at the C-terminal but not at the N-terminal domain of the NMDA receptor NR1 is altered in the kindled hippocampus. Eur. J. Neurosci. 7, 2513–2517 (1995).

    Article  CAS  PubMed  Google Scholar 

  55. Wang, Z. & Grabowski, P. J. Cell- and stage-specific splicing events resolved in specialized neurons of the rat cerebellum. RNA 2, 1241–1253 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Black, D. L. Mechanisms of alternative pre-messenger RNA splicing. Annu. Rev. Biochem. 72, 291–336 (2003).

    Article  CAS  PubMed  Google Scholar 

  57. Young, J. I. et al. Regulation of RNA splicing by the methylation-dependent transcriptional repressor methyl-CpG binding protein 2. Proc. Natl Acad. Sci. USA 102, 17551–17558 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  58. Edwalds-Gilbert, G., Veraldi, K. L. & Milcarek, C. Alternative poly(A) site selection in complex transcription units: means to an end? Nucleic Acids Res. 25, 2547–2561 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Balmer, D., Goldstine, J., Rao, Y. M. & LaSalle, J. M. Elevated methyl-CpG-binding protein 2 expression is acquired during postnatal human brain development and is correlated with alternative polyadenylation. J. Mol. Med. 81, 61–68 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Pelka, G. J., Watson, C. M., Christodoulou, J. & Tam, P. P. Distinct expression profiles of Mecp2 transcripts with different lengths of 3′UTR in the brain and visceral organs during mouse development. Genomics 85, 441–452 (2005).

    Article  CAS  PubMed  Google Scholar 

  61. Zhang, H., Lee, J. Y. & Tian, B. Biased alternative polyadenylation in human tissues. Genome Biol. 6, R100 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. de Moor, C. H., Meijer, H. & Lissenden, S. Mechanisms of translational control by the 3′ UTR in development and differentiation. Semin. Cell Dev. Biol. 16, 49–58 (2005).

    Article  CAS  PubMed  Google Scholar 

  63. Keegan, L. P., Gallo, A. & O'Connell, M. A. The many roles of an RNA editor. Nature Rev. Genet. 2, 869–878 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Paul, M. S. & Bass, B. L. Inosine exists in mRNA at tissue-specific levels and is most abundant in brain mRNA. EMBO J. 17, 1120–1127 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Tonkin, L. A. et al. RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans. EMBO J. 21, 6025–6035 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Palladino, M. J., Keegan, L. P., O'Connell, M. A. & Reenan, R. A. A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102, 437–449 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Keegan, L. P., Gallo, A. & O'Connell, M. A. Development. Survival is impossible without an editor. Science 290, 1707–1709 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Dingledine, R., Borges, K., Bowie, D. & Traynelis, S. F. The glutamate receptor ion channels. Pharmacol. Rev. 51, 7–61 (1999).

    CAS  PubMed  Google Scholar 

  69. Vissel, B. et al. The role of RNA editing of kainate receptors in synaptic plasticity and seizures. Neuron 29, 217–227 (2001).

    Article  CAS  PubMed  Google Scholar 

  70. Kwak, S. & Kawahara, Y. Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis. J. Mol. Med. 83, 110–120 (2005).

    Article  CAS  PubMed  Google Scholar 

  71. Niswender, C. M., Copeland, S. C., Herrick-Davis, K., Emeson, R. B. & Sanders-Bush, E. RNA editing of the human serotonin 5-hydroxytryptamine 2C receptor silences constitutive activity. J. Biol. Chem. 274, 9472–9478 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Niswender, C. M. et al. RNA editing of the human serotonin 5-HT2C receptor: alterations in suicide and implications for serotonergic pharmacotherapy. Neuropsychopharmacology 24, 478–491 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Akbarian, S., Smith, M. A. & Jones, E. G. Editing for an AMPA receptor subunit RNA in prefrontal cortex and striatum in Alzheimer's disease, Huntington's disease and schizophrenia. Brain Res. 699, 297–304 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. Gurevich, I. et al. Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims. Neuron 34, 349–356 (2002).

    Article  CAS  PubMed  Google Scholar 

  75. Grant, S. G. The synapse proteome and phosphoproteome: a new paradigm for synapse biology. Biochem. Soc. Trans. 34, 59–63 (2006).

    Article  CAS  PubMed  Google Scholar 

  76. Flavell, S. W. et al. Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science 311, 1008–1012 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  77. Shalizi, A. et al. A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation. Science 311, 1012–1017 (2006).

    Article  ADS  CAS  PubMed  Google Scholar 

  78. Gottesman, I. I. & Hanson, D. R. Human development: biological and genetic processes. Annu. Rev. Psychol. 56, 263–286 (2005).

    Article  PubMed  Google Scholar 

  79. Branchi, I., Francia, N. & Alleva, E. Epigenetic control of neurobehavioural plasticity: the role of neurotrophins. Behav. Pharmacol. 15, 353–362 (2004).

    Article  CAS  PubMed  Google Scholar 

  80. Sims, R. J., Nishioka, K. & Reinberg, D. Histone lysine methylation: a signature for chromatin function. Trends Genet. 19, 629–639 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Stadler, F. et al. Histone methylation at gene promoters is associated with developmental regulation and region-specific expression of ionotropic and metabotropic glutamate receptors in human brain. J. Neurochem. 94, 324–336 (2005).

    Article  CAS  PubMed  Google Scholar 

  82. Karlsson, H. et al. Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia. Proc. Natl Acad. Sci. USA 98, 4634–4639 (2001).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yee, F. & Yolken, R. H. Identification of differentially expressed RNA transcripts in neuropsychiatric disorders. Biol. Psychiatry 41, 759–761 (1997).

    Article  CAS  PubMed  Google Scholar 

  84. Kim, H. S., Takenaka, O. & Crow, T. J. Isolation and phylogeny of endogenous retrovirus sequences belonging to the HERV-W family in primates. J. Gen. Virol. 80, 2613–2619 (1999).

    Article  CAS  PubMed  Google Scholar 

  85. Frank, O. et al. Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders. J. Virol. 79, 10890–10901 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yolken, R. H., Karlsson, H., Yee, F., Johnston-Wilson, N. L. & Torrey, E. F. Endogenous retroviruses and schizophrenia. Brain Res. Brain Res. Rev. 31, 193–199 (2000).

    Article  CAS  PubMed  Google Scholar 

  87. Kan, P. X., Popendikyte, V., Kaminsky, Z. A., Yolken, R. H. & Petronis, A. Epigenetic studies of genomic retroelements in major psychosis. Schizophr. Res. 67, 95–106 (2004).

    Article  PubMed  Google Scholar 

  88. Cao, X., Yeo, G., Muotri, A. R., Kuwabara, T. & Gage, F. H. Noncoding RNAs in the mammalian central nervous system. Annu. Rev. Neurosci. Published online 15 Mar 2006 (doi:10.1146/annurev.neuro.29.051605.112839).

  89. Kosik, K. S. & Krichevsky, A. M. The elegance of the microRNAs: a neuronal perspective. Neuron 47, 779–782 (2005).

    Article  CAS  PubMed  Google Scholar 

  90. Pasquinelli, A. E., Hunter, S. & Bracht, J. MicroRNAs: a developing story. Curr. Opin. Genet. Dev. 15, 200–205 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. Kuwabara, T., Hsieh, J., Nakashima, K., Taira, K. & Gage, F. H. A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 116, 779–793 (2004).

    Article  CAS  PubMed  Google Scholar 

  93. Belancio, V. P., Hedges, D. J. & Deininger, P. LINE-1 RNA splicing and influences on mammalian gene expression. Nucleic Acids Res. 34, 1512–1521 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Roy-Engel, A. M. et al. Human retroelements may introduce intragenic polyadenylation signals. Cytogenet. Genome Res. 110, 365–371 (2005).

    Article  CAS  PubMed  Google Scholar 

  95. Meischl, C., Boer, M., Ahlin, A. & Roos, D. A new exon created by intronic insertion of a rearranged LINE-1 element as the cause of chronic granulomatous disease. Eur. J. Hum. Genet. 8, 697–703 (2000).

    Article  CAS  PubMed  Google Scholar 

  96. Francesconi, A. & Duvoisin, R. M. Alternative splicing unmasks dendritic and axonal targeting signals in metabotropic glutamate receptor 1. J. Neurosci. 22, 2196–2205 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

A.R.M. is a Pew Latin American Fellow. F.H.G. was supported by the Lookout Fund, and the National Institutes of Health National Institute on Aging and National Institute of Neurological Disorders and Stroke. The authors would like to thank M. L. Gage for editorial comments, and N. Spitzer and members of the Gage laboratory for critical comments on the manuscript. We regret that, owing to space limitations, we have been unable to refer to all of the primary literature and have had to rely instead, in many instances, on reviews.

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    Alysson R. Muotri & Fred H. Gage

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Correspondence to Fred H. Gage.

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Muotri, A., Gage, F. Generation of neuronal variability and complexity. Nature 441, 1087–1093 (2006). https://doi.org/10.1038/nature04959

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