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  • Review Article
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Roles of small regulatory RNAs in determining neuronal identity

Nature Reviews Neuroscience volume 11, pages 329–338 (2010)Cite this article

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A Corrigendum to this article was published on 01 June 2010

This article has been updated

Key Points

  • The small regulatory RNAs identified so far include microRNAs (miRNAs), endogenous small interfering RNAs (esiRNAs), Piwi-interacting RNAs (piRNAs) and promoter-associated short RNAs (PASRs; also known as transcription start site RNAs (TSS RNAs) and transcription initiation RNAs (tiRNAs)). These small RNAs range from 18–30 nucleotides in length and can modulate diverse cellular pathways.

  • The specific expression of miRNA in the nervous system suggests that miRNAs could play key parts in brain development and neuronal fate specification.

  • It has been shown that transcription factors can directly regulate the expression of specific miRNAs and that specific miRNAs can then target other transcription factors and regulate their expression post-transcriptionally. The result is a transcription factor to miRNA to another transcription factor (sometimes even of the miRNA itself) paradigm for regulating neurogenesis.

  • During neurogenesis, miRNAs may act through feedback loops to reinforce and stabilize changes in gene expression in response to signalling input.

  • Recent evidence suggests that an epigenetic circuitory with a feedback regulatory mechanism mediated by miRNAs is involved in the regulation of neurogenesis.

  • miRNAs that determine the lineage specificity of both astrocytes and oligodendrocytes have been identified.

  • Other types of small regulatory RNAs could also be involved in regulating neurogenesis. Powerful deep-sequencing technologies should enable the identification of many more small regulatory RNAs that are involved in regulating neurogenesis.

Abstract

Neurogenesis, the process of generating functional neurons from neural stem cells, is tightly controlled by many intrinsic and extrinsic mechanisms. Uncovering these regulatory mechanisms is crucial for understanding the functions and plasticity of the human brain. Recent studies in both invertebrates and vertebrates point to the importance of small regulatory RNAs in regulating lineage-specific gene expression and determining neuronal identity during neurogenesis. These new observations suggest that small regulatory RNAs could function at many levels to regulate self-renewal of neural stem cells and neuronal fate specification, implicating small regulatory RNAs in the complexity of neurogenesis.

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Figure 1: Embryonic and adult neurogenesis.
Figure 2: Role of miRNAs in fine-tuning neurogenesis.
Figure 3: A model of neuronal diversity generated by L1 retrotransposition.

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Change history

  • 30 April 2010

    On page 331 of the above article, we wrote that: "Surprisingly, these defects could be partially rescued by a single miRNA, miR-340 (Ref. 17)." This should have read: "Surprisingly, these defects could be partially rescued by a single miRNA, miR-430 ((Ref. 17)." The authors apologize for this error.

References

  1. Ming, G. L. & Song, H. Adult neurogenesis in the mammalian central nervous system. Annu. Rev. Neurosci. 28, 223–250 (2005).

    Article  CAS  PubMed  Google Scholar 

  2. Zhao, C., Deng, W. & Gage, F. H. Mechanisms and functional implications of adult neurogenesis. Cell 132, 645–660 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Mattick, J. S. The functional genomics of noncoding RNA. Science 309, 1527–1528 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. Gangaraju, V. K. & Lin, H. MicroRNAs: key regulators of stem cells. Nature Rev. Mol. Cell Biol. 10, 116–125 (2009).

    Article  CAS  Google Scholar 

  5. Stadler, B. M. & Ruohola-Baker, H. Small RNAs: keeping stem cells in line. Cell 132, 563–566 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kapsimali, M. et al. MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system. Genome Biol. 8, R173 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Krichevsky, A. M., King, K. S., Donahue, C. P., Khrapko, K. & Kosik, K. S. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9, 1274–1281 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lagos-Quintana, M. et al. Identification of tissue-specific microRNAs from mouse. Curr. Biol. 12, 735–739 (2002). This is the first paper to report the tissue-specific expression of miRNAs in mammals.

    Article  CAS  PubMed  Google Scholar 

  9. Sempere, L. F. et al. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol. 5, R13 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Smirnova, L. et al. Regulation of miRNA expression during neural cell specification. Eur. J. Neurosci. 21, 1469–1477 (2005).

    Article  PubMed  Google Scholar 

  11. Lagos-Quintana, M., Rauhut, R., Lendeckel, W. & Tuschl, T. Identification of novel genes coding for small expressed RNAs. Science 294, 853–858 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Landgraf, P. et al. A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129, 1401–1414 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wulczyn, F. G. et al. Post-transcriptional regulation of the let-7 microRNA during neural cell specification. FASEB J. 21, 415–426 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Wienholds, E. & Plasterk, R. H. MicroRNA function in animal development. FEBS Lett. 579, 5911–5922 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Wienholds, E. et al. MicroRNA expression in zebrafish embryonic development. Science 309, 310–311 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Krichevsky, A. M., Sonntag, K. C., Isacson, O. & Kosik, K. S. Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 24, 857–864 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Giraldez, A. J. et al. MicroRNAs regulate brain morphogenesis in zebrafish. Science 308, 833–838 (2005). This study provides the first in vivo evidence that miRNAs are crucial for brain development.

    Article  CAS  PubMed  Google Scholar 

  18. Liu, J. et al. Argonaute2 is the catalytic engine of mammalian RNAi. Science 305, 1437–1441 (2004).

    Article  CAS  PubMed  Google Scholar 

  19. Cuellar, T. L. et al. Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration. Proc. Natl Acad. Sci. USA 105, 5614–5619 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Davis, T. H. et al. Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J. Neurosci. 28, 4322–4330 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. De Pietri Tonelli, D. et al. miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex. Development 135, 3911–3921 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Kawase-Koga, Y., Otaegi, G. & Sun, T. Different timings of Dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system. Dev. Dyn. 238, 2800–2812 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gotz, M. & Huttner, W. B. The cell biology of neurogenesis. Nature Rev. Mol. Cell Biol. 6, 777–788 (2005).

    Article  CAS  Google Scholar 

  24. Neumuller, R. A. & Knoblich, J. A. Dividing cellular asymmetry: asymmetric cell division and its implications for stem cells and cancer. Genes Dev. 23, 2675–2699 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Zhong, W. & Chia, W. Neurogenesis and asymmetric cell division. Curr. Opin. Neurobiol. 18, 4–11 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Schwamborn, J. C., Berezikov, E. & Knoblich, J. A. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136, 913–925 (2009). This paper was the first to show that a miRNA-containing ribonucleoprotein complex could be unequally distributed and contribute to asymmetrical cell division.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Loedige, I. & Filipowicz, W. TRIM-NHL proteins take on miRNA regulation. Cell 136, 818–820 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Cao, X., Yeo, G., Muotri, A. R., Kuwabara, T. & Gage, F. H. Noncoding RNAs in the mammalian central nervous system. Annu. Rev. Neurosci. 29, 77–103 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Fineberg, S. K., Kosik, K. S. & Davidson, B. L. MicroRNAs potentiate neural development. Neuron 64, 303–309 (2009).

    Article  CAS  PubMed  Google Scholar 

  30. Kosik, K. S. The neuronal microRNA system. Nature Rev. Neurosci. 7, 911–920 (2006).

    Article  CAS  Google Scholar 

  31. Schratt, G. microRNAs at the synapse. Nature Rev. Neurosci. 10, 842–849 (2009).

    Article  CAS  Google Scholar 

  32. Coolen, M. & Bally-Cuif, L. MicroRNAs in brain development and physiology. Curr. Opin. Neurobiol. 19, 461–470 (2009).

    Article  CAS  PubMed  Google Scholar 

  33. Chang, S., Johnston, R. J. Jr, Frokjaer-Jensen, C., Lockery, S. & Hobert, O. MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode. Nature 430, 785–789 (2004).

    Article  CAS  PubMed  Google Scholar 

  34. Johnston, R. J. & Hobert, O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426, 845–849 (2003). References 33 and 34 provide the first evidence that miRNAs regulate neuronal fate determination.

    Article  CAS  PubMed  Google Scholar 

  35. Johnston, R. J. Jr, Chang, S., Etchberger, J. F., Ortiz, C. O. & Hobert, O. MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision. Proc. Natl Acad. Sci. USA 102, 12449–12454 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lim, L. P. et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769–773 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Makeyev, E. V., Zhang, J., Carrasco, M. A. & Maniatis, T. The microRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol. Cell 27, 435–448 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ballas, N., Grunseich, C., Lu, D. D., Speh, J. C. & Mandel, G. REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121, 645–657 (2005).

    Article  CAS  PubMed  Google Scholar 

  39. Visvanathan, J., Lee, S., Lee, B., Lee, J. W. & Lee, S. K. The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev. 21, 744–749 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Conaco, C., Otto, S., Han, J. J. & Mandel, G. Reciprocal actions of REST and a microRNA promote neuronal identity. Proc. Natl Acad. Sci. USA 103, 2422–2427 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Cheng, L. C., Pastrana, E., Tavazoie, M. & Doetsch, F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nature Neurosci. 12, 399–408 (2009).

    Article  CAS  PubMed  Google Scholar 

  42. Kloosterman, W. P. et al. Cloning and expression of new microRNAs from zebrafish. Nucleic Acids Res. 34, 2558–2569 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li, Y., Wang, F., Lee, J. A. & Gao, F. B. MicroRNA-9a ensures the precise specification of sensory organ precursors in Drosophila. Genes Dev. 20, 2793–2805 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Leucht, C. et al. MicroRNA-9 directs late organizer activity of the midbrain–hindbrain boundary. Nature Neurosci. 11, 641–648 (2008).

    Article  CAS  PubMed  Google Scholar 

  45. Shibata, M., Kurokawa, D., Nakao, H., Ohmura, T. & Aizawa, S. MicroRNA-9 modulates Cajal-Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium. J. Neurosci. 28, 10415–10421 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sun, G., Yu, R. T., Evans, R. M. & Shi, Y. Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc. Natl Acad. Sci. USA 104, 15282–15287 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhao, C., Sun, G., Li, S. & Shi, Y. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. Nature Struct. Mol. Biol. 16, 365–371 (2009).

    Article  CAS  Google Scholar 

  48. Ruiz i Altaba, A., Palma, V. & Dahmane, N. Hedgehog–Gli signalling and the growth of the brain. Nature Rev. Neurosci. 3, 24–33 (2002).

    Article  CAS  Google Scholar 

  49. Decembrini, S. et al. MicroRNAs couple cell fate and developmental timing in retina. Proc. Natl Acad. Sci. USA 106, 21179–21184 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Ferretti, E. et al. Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J. 27, 2616–2627 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Northcott, P. A. et al. The miR-17/92 polycistron is up-regulated in sonic hedgehog-driven medulloblastomas and induced by N-myc in sonic hedgehog-treated cerebellar neural precursors. Cancer Res. 69, 3249–3255 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Li, X. & Carthew, R. W. A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye. Cell 123, 1267–1277 (2005). This paper was the first to show that miRNAs regulate neuronal fate through EGF receptor signalling.

    Article  CAS  PubMed  Google Scholar 

  53. Li, X. & Zhao, X. Epigenetic regulation of mammalian stem cells. Stem Cells Dev. 17, 1043–1052 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mehler, M. F. Epigenetics and the nervous system. Ann. Neurol. 64, 602–617 (2008).

    Article  CAS  PubMed  Google Scholar 

  55. Bernstein, B. E., Meissner, A. & Lander, E. S. The mammalian epigenome. Cell 128, 669–681 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Lim, D. A. et al. Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature 458, 529–533 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ma, D. K. et al. Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323, 1074–1077 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Zhao, X. et al. Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function. Proc. Natl Acad. Sci. USA 100, 6777–6782 (2003). References 56–58 show the key role of epigenetic regulation in neurogenesis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Cheng, L. C., Tavazoie, M. & Doetsch, F. Stem cells: from epigenetics to microRNAs. Neuron 46, 363–367 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Hsieh, J. & Gage, F. H. Epigenetic control of neural stem cell fate. Curr. Opin. Genet. Dev. 14, 461–469 (2004).

    Article  CAS  PubMed  Google Scholar 

  61. Abel, T. & Zukin, R. S. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr. Opin. Pharmacol. 8, 57–64 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tijsterman, M., Ketting, R. F. & Plasterk, R. H. A. The genetics of RNA silencing. Annu. Rev. Genet. 36, 489–519 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. Morris, K. V., Chan, S. W., Jacobsen, S. E. & Looney, D. J. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305, 1289–1292 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Kawasaki, H. & Taira, K. Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature 431, 211–217 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Klein, M. E. et al. Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA. Nature Neurosci. 10, 1513–1514 (2007).

    Article  CAS  PubMed  Google Scholar 

  66. Nomura, T. et al. MeCP2-dependent repression of an imprinted miR-184 released by depolarization. Hum. Mol. Genet. 17, 1192–1199 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 16, 6–21 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Amir, R. E. et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature Genet. 23, 185–188 (1999).

    Article  CAS  PubMed  Google Scholar 

  69. Chahrour, M. & Zoghbi, H. Y. The story of Rett syndrome: from clinic to neurobiology. Neuron 56, 422–437 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Godlewski, J. et al. Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res. 68, 9125–9130 (2008).

    Article  CAS  PubMed  Google Scholar 

  71. Yoo, A. S., Staahl, B. T., Chen, L. & Crabtree, G. R. MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature 460, 642–646 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lau, P. et al. Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes. J. Neurosci. 28, 11720–11730 (2008). The first paper to report the potential involvement of miRNAs in the development of oligodendrocytes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kawamura, Y. et al. Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells. Nature 453, 793–797 (2008).

    Article  CAS  PubMed  Google Scholar 

  74. Czech, B. et al. An endogenous small interfering RNA pathway in Drosophila. Nature 453, 798–802 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Okamura, K. & Lai, E. C. Endogenous small interfering RNAs in animals. Nature Rev. Mol. Cell Biol. 9, 673–678 (2008).

    Article  CAS  Google Scholar 

  76. Aravin, A. A., Hannon, G. J. & Brennecke, J. The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 318, 761–764 (2007).

    Article  CAS  PubMed  Google Scholar 

  77. Coufal, N. G. et al. L1 retrotransposition in human neural progenitor cells. Nature 460, 1127–1131 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Muotri, A. R. et al. Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition. Nature 435, 903–910 (2005). References 77 and 78 show that retrotransposition of the L1 element occurs in human and rodent NPCs, which could contribute to neuronal diversity.

    Article  CAS  PubMed  Google Scholar 

  79. Kuwabara, T. et al. Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nature Neurosci. 12, 1097–1105 (2009).

    Article  CAS  PubMed  Google Scholar 

  80. Muotri, A. R. & Gage, F. H. Generation of neuronal variability and complexity. Nature 441, 1087–1093 (2006).

    Article  CAS  PubMed  Google Scholar 

  81. Yang, N. & Kazazian, H. H. Jr. L1 retrotransposition is suppressed by endogenously encoded small interfering RNAs in human cultured cells. Nature Struct. Mol. Biol. 13, 763–771 (2006).

    Article  CAS  Google Scholar 

  82. Kapranov, P. et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316, 1484–1488 (2007).

    Article  CAS  PubMed  Google Scholar 

  83. Taft, R. J. et al. Tiny RNAs associated with transcription start sites in animals. Nature Genet. 41, 572–578 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. 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 

  85. Bushati, N. & Cohen, S. M. microRNA functions. Annu. Rev. Cell Dev. Biol. 23, 175–205 (2007).

    Article  CAS  PubMed  Google Scholar 

  86. Bartel, D. P. MicroRNAs: target recognition and regulatory functions. Cell 136, 215–233 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Rybak, A. et al. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nature Cell Biol. 10, 987–993 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. Sawamoto, K. et al. New neurons follow the flow of cerebrospinal fluid in the adult brain. Science 311, 629–632 (2006).

    Article  CAS  PubMed  Google Scholar 

  89. Shen, Q. et al. Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3, 289–300 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Tavazoie, M. et al. A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3, 279–288 (2008). References 89 and 90 provide evidence that the vasculature is an important component of neurogenic niches in the adult mammalian brain.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ghildiyal, M. & Zamore, P. D. Small silencing RNAs: an expanding universe. Nature Rev. Genet. 10, 94–108 (2009).

    Article  CAS  PubMed  Google Scholar 

  92. Kim, V. N., Han, J. & Siomi, M. C. Biogenesis of small RNAs in animals. Nature Rev. Mol. Cell Biol. 10, 126–139 (2009).

    Article  CAS  Google Scholar 

  93. Mardis, E. R. Next-generation DNA sequencing methods. Annu. Rev. Genomics Hum. Genet. 9, 387–402 (2008).

    Article  CAS  PubMed  Google Scholar 

  94. Metzker, M. L. Sequencing technologies — the next generation. Nature Rev. Genet. 11, 31–46 (2010).

    Article  CAS  PubMed  Google Scholar 

  95. Rusk, N. & Kiermer, V. Primer: Sequencing — the next generation. Nature Methods 5, 15 (2008).

    Article  CAS  PubMed  Google Scholar 

  96. Maller Schulman, B. R. et al. The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure. Cell Cycle 7, 3935–3942 (2008).

    Article  PubMed  Google Scholar 

  97. Beveridge, N. J., Tooney, P. A., Carroll, A. P., Tran, N. & Cairns, M. J. Down-regulation of miR-17 family expression in response to retinoic acid induced neuronal differentiation. Cell Signal. 21, 1837–1845 (2009).

    Article  CAS  PubMed  Google Scholar 

  98. Kawasaki, H. & Taira, K. Hes1 is a target of microRNA-23 during retinoic-acid-induced neuronal differentiation of NT2 cells. Nature 423, 838–842 (2003).

    Article  CAS  PubMed  Google Scholar 

  99. Le, M. T. et al. MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets. Mol. Cell. Biol. 29, 5290–5305 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Choi, P. S. et al. Members of the miRNA-200 family regulate olfactory neurogenesis. Neuron 57, 41–55 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Cayirlioglu, P. et al. Hybrid neurons in a microRNA mutant are putative evolutionary intermediates in insect CO2 sensory systems. Science 319, 1256–1260 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Dugas, J. C. et al. Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination. Neuron 65, 597–611 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhao, X. et al. MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 65, 612–626 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank C. Strauss for critical reading of the manuscript. We apologize to those whose works are not cited here owing space limitations. The work in our laboratory was supported in part by the grants from the National Institutes of Health and International Rett Syndrome Foundation. P.J. is a recipient of the Beckman Young Investigator Award and the Basil O'Connor Scholar Research Award, as well as an Alfred P. Sloan Research Fellowship in Neuroscience. X.L. is supported by a FRAXA Fellowship.

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  1. Department of Human Genetics, Emory University School of Medicine, 615 Michael Street, Suite 301, Atlanta, 30322, Georgia, USA

    Xuekun Li & Peng Jin

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Glossary

Self-renewal

The capacity of a cell to proliferate and produce identical cells.

Multipotency

The potential of a cell to give rise to multiple lineage cells. Neural stem cells, for example can generate neurons, astrocytes and oligodendrocytes.

Deep sequencing

An approach enabled by next-generation sequencing technology that is particularly useful for identifying low-abundance RNAs or low-frequency mutations.

Cre–loxP system

A site-specific recombination system derived from Escherichia coli bacteriophage P1. Two short DNA sequences (loxP sites) are engineered to flank the target DNA. Activation of the Cre-recombinase enzyme catalyses recombination between the loxP sites, leading to excision of the intervening DNA sequence.

Environmental enrichment

Providing animals under managed care with environmental stimuli to improve the quality of life by increasing physical activity, stimulating natural behaviours and preventing or reducing neural disorders including stereotypical behaviours.

Transit-amplifying cells

Cells that arise from adult stem cells and divide a finite number of times until they become differentiated. They are committed progenitor cells.

Locked nucleic acid

A modified RNA nucleotide with high stability, which can be used as a highly sensitive detection probe.

A2B5

A cell surface ganglioside epitope expressed in developing thymic epithelial cells, oligodendrocyte progenitors and neuroendocrine cells.

Long interspersed nuclear (L1) elements

Full-length active L1 elements are ∼6 kb long, consisting of a 5′-untranslated region that has promoter activity, two open reading frames (encoding a nucleic acid-binding protein and an endonuclease), a reverse transcriptase protein and a poly(A) tail.

Retrotransposon

Genetic elements that can amplify themselves in a genome through an RNA intermediate. They are ubiquitous components of the DNA of many eukaryotic organisms.

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Li, X., Jin, P. Roles of small regulatory RNAs in determining neuronal identity. Nat Rev Neurosci 11, 329–338 (2010). https://doi.org/10.1038/nrn2739

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