Skip to main content

Understanding the Role of lncRNAs in Nervous System Development

  • Chapter
  • First Online:
Long Non Coding RNA Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1008))

Abstract

The diversity of lncRNAs has expanded within mammals in tandem with the evolution of increased brain complexity, suggesting that lncRNAs play an integral role in this process. In this chapter, we will highlight the identification and characterization of lncRNAs in nervous system development. We discuss the potential role of lncRNAs in nervous system and brain evolution, along with efforts to create comprehensive catalogues that analyze spatial and temporal changes in lncRNA expression during nervous system development. Additionally, we focus on recent endeavors that attempt to assign function to lncRNAs during nervous system development. We highlight discrepancies that have been observed between in vitro and in vivo studies of lncRNA function and the challenges facing researchers in conducting mechanistic analyses of lncRNAs in the developing nervous system. Altogether, this chapter highlights the emerging role of lncRNAs in the developing brain and sheds light on novel, RNA-mediated mechanisms by which nervous system development is controlled.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Arendt D, Denes AS, Jekely G, Tessmar-Raible K (2008) The evolution of nervous system centralization. Philos Trans R Soc Lond Ser B Biol Sci 363(1496):1523–1528

    Article  Google Scholar 

  2. Hirth F (2010) On the origin and evolution of the tripartite brain. Brain Behav Evol 76(1):3–10

    Article  PubMed  Google Scholar 

  3. Galliot B, Quiquand M, Ghila L, de Rosa R, Miljkovic-Licina M, Chera S (2009) Origins of neurogenesis, a cnidarian view. Dev Biol 332(1):2–24

    Article  CAS  PubMed  Google Scholar 

  4. Nakanishi N, Renfer E, Technau U, Rentzsch F (2012) Nervous systems of the sea anemone Nematostella vectensis are generated by ectoderm and endoderm and shaped by distinct mechanisms. Development 139(2):347–357

    Article  CAS  PubMed  Google Scholar 

  5. Ohno S (1970) Evolution by gene duplication. Springer, Berlin

    Book  Google Scholar 

  6. Zhang J (2003) Evolution by gene duplication: an update. TRENDS Ecol Evol 18(6):292–298

    Article  Google Scholar 

  7. Betizeau M, Cortay V, Patti D, Pfister S, Gautier E, Bellemin-Menard A, Afanassieff M, Huissoud C, Douglas RJ, Kennedy H, Dehay C (2013) Precursor diversity and complexity of lineage relationships in the outer subventricular zone of the primate. Neuron 80(2):442–457

    Article  CAS  PubMed  Google Scholar 

  8. Borrell V, Calegari F (2014) Mechanisms of brain evolution: regulation of neural progenitor cell diversity and cell cycle length. Neurosci Res 86:14–24

    Article  PubMed  Google Scholar 

  9. Florio M, Huttner WB (2014) Neural progenitors, neurogenesis and the evolution of the neocortex. Development 141(11):2182–2194

    Article  CAS  PubMed  Google Scholar 

  10. Lewitus E, Kelava I, Huttner WB (2013) Conical expansion of the outer subventricular zone and the role of neocortical folding in evolution and development. Front Hum Neurosci 7:424

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lewitus E, Kelava I, Kalinka AT, Tomancak P, Huttner WB (2014) An adaptive threshold in mammalian neocortical evolution. PLoS Biol 12(11):e1002000

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Lui JH, Hansen DV, Kriegstein AR (2011) Development and evolution of the human neocortex. Cell 146(1):18–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Stahl R, Walcher T, De Juan Romero C, Pilz GA, Cappello S, Irmler M, Sanz-Aquela JM, Beckers J, Blum R, Borrell V, Gotz M (2013) Trnp1 regulates expansion and folding of the mammalian cerebral cortex by control of radial glial fate. Cell 153(3):535–549

    Article  CAS  PubMed  Google Scholar 

  14. Sun T, Hevner RF (2014) Growth and folding of the mammalian cerebral cortex: from molecules to malformations. Nat Rev Neurosci 15(4):217–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kaskan PM, Finlay BL (2001) Bigger is better: primate brain size in relationship to cognition. In: Falk D, Gibson KR (eds) Evolutionary anatomy of the primate cerebral cortex. Cambridge University Press, Cambridge, pp 79–97

    Google Scholar 

  16. Finlay BL, Darlington RB (1995) Linked regularities in the development and evolution of mammalian brains. Science (New York, NY) 268(5217):1578–1584

    Article  CAS  Google Scholar 

  17. Roth G, Dicke U (2005) Evolution of the brain and intelligence. Trends Cogn Sci 9(5):250–257

    Article  PubMed  Google Scholar 

  18. Jerison HJ (1973) Evolution of the brain and intelligence, XIV edn. Academic, New York

    Google Scholar 

  19. Derrien T, Johnson R, Bussotti G, Tanzer A, Djebali S, Tilgner H, Guernec G, Martin D, Merkel A, Knowles DG, Lagarde J, Veeravalli L, Ruan X, Ruan Y, Lassmann T, Carninci P, Brown JB, Lipovich L, Gonzalez JM, Thomas M, Davis CA, Shiekhattar R, Gingeras TR, Hubbard TJ, Notredame C, Harrow J, Guigo R (2012) The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22(9):1775–1789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Harrow J, Frankish A, Gonzalez JM, Tapanari E, Diekhans M, Kokocinski F, Aken BL, Barrell D, Zadissa A, Searle S, Barnes I, Bignell A, Boychenko V, Hunt T, Kay M, Mukherjee G, Rajan J, Despacio-Reyes G, Saunders G, Steward C, Harte R, Lin M, Howald C, Tanzer A, Derrien T, Chrast J, Walters N, Balasubramanian S, Pei B, Tress M, Rodriguez JM, Ezkurdia I, van Baren J, Brent M, Haussler D, Kellis M, Valencia A, Reymond A, Gerstein M, Guigo R, Hubbard TJ (2012) GENCODE: the reference human genome annotation for the ENCODE project. Genome Res 22(9):1760–1774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Necsulea A, Soumillon M, Warnefors M, Liechti A, Daish T, Zeller U, Baker JC, Grutzner F, Kaessmann H (2014) The evolution of lncRNA repertoires and expression patterns in tetrapods. Nature 505(7485):635–640

    Article  CAS  PubMed  Google Scholar 

  22. Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A 105(2):716–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Luo H, Sun S, Li P, Bu D, Cao H, Zhao Y (2013) Comprehensive characterization of 10,571 mouse large intergenic noncoding RNAs from whole transcriptome sequencing. PLoS One 8(8):e70835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ponjavic J, Oliver PL, Lunter G, Ponting CP (2009) Genomic and transcriptional co-localization of protein-coding and long non-coding RNA pairs in the developing brain. PLoS Genet 5(8):e1000617

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Francescatto M, Vitezic M, Heutink P, Saxena A (2014) Brain-specific noncoding RNAs are likely to originate in repeats and may play a role in up-regulating genes in cis. Int J Biochem Cell Biol 54:331–337

    Article  CAS  PubMed  Google Scholar 

  26. Kaushik K, Leonard VE, Kv S, Lalwani MK, Jalali S, Patowary A, Joshi A, Scaria V, Sivasubbu S (2013) Dynamic expression of long non-coding RNAs (lncRNAs) in adult zebrafish. PLoS One 8(12):e83616

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Washietl S, Kellis M, Garber M (2014) Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals. Genome Res 24(4):616–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kelley D, Rinn J (2012) Transposable elements reveal a stem cell-specific class of long noncoding RNAs. Genome Biol 13(11):R107. doi:10.1186/gb-2012-13-11-r107

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell 147(7):1537–1550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lipovich L, Hou ZC, Jia H, Sinkler C, McGowen M, Sterner KN, Weckle A, Sugalski AB, Pipes L, Gatti DL, Mason CE, Sherwood CC, Hof PR, Kuzawa CW, Grossman LI, Goodman M, Wildman DE (2016) High-throughput RNA sequencing reveals structural differences of orthologous brain-expressed genes between western lowland gorillas and humans. J Comp Neurol 524(2):288–308

    Article  CAS  PubMed  Google Scholar 

  31. Basu S, Muller F, Sanges R (2013) Examples of sequence conservation analyses capture a subset of mouse long non-coding RNAs sharing homology with fish conserved genomic elements. BMC Bioinformatics 14(Suppl 7):S14. doi:10.1186/1471-2105-14-S7-S14. Epub 2013 Apr 22.

    PubMed  PubMed Central  Google Scholar 

  32. He Z, Bammann H, Han D, Xie G, Khaitovich P (2014) Conserved expression of lincRNA during human and macaque prefrontal cortex development and maturation. RNA (New York, NY) 20(7):1103–1111

    Article  CAS  Google Scholar 

  33. Bird CP, Stranger BE, Liu M, Thomas DJ, Ingle CE, Beazley C, Miller W, Hurles ME, Dermitzakis ET (2007) Fast-evolving noncoding sequences in the human genome. Genome Biol 8(6):R118

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Bush EC, Lahn BT (2008) A genome-wide screen for noncoding elements important in primate evolution. BMC Evol Biol 8:17. doi:10.1186/1471-2148-8-17

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, Haussler D (2006) An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443(7108):167–172

    Article  CAS  PubMed  Google Scholar 

  36. Prabhakar S, Visel A, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Morrison H, Fitzpatrick DR, Afzal V, Pennacchio LA, Rubin EM, Noonan JP (2008) Human-specific gain of function in a developmental enhancer. Science (New York, NY) 321(5894):1346–1350

    Article  CAS  Google Scholar 

  37. Capra JA, Erwin GD, McKinsey G, Rubenstein JL, Pollard KS (2013) Many human accelerated regions are developmental enhancers. Philos Trans R Soc Lond Ser B Biol Sci 368(1632):20130025

    Article  CAS  Google Scholar 

  38. Meyer G, Soria JM, Martinez-Galan JR, Martin-Clemente B, Fairen A (1998) Different origins and developmental histories of transient neurons in the marginal zone of the fetal and neonatal rat cortex. J Comp Neurol 397(4):493–518

    Article  CAS  PubMed  Google Scholar 

  39. Rakic S, Zecevic N (2003) Emerging complexity of layer I in human cerebral cortex. Cereb Cortex (New York, NY: 1991) 13(10):1072–1083

    Google Scholar 

  40. Meyer G, Wahle P (1999) The paleocortical ventricle is the origin of reelin-expressing neurons in the marginal zone of the foetal human neocortex. Eur J Neurosci 11(11):3937–3944

    Article  CAS  PubMed  Google Scholar 

  41. Zecevic N, Rakic P (2001) Development of layer I neurons in the primate cerebral cortex. J Neurosci 21(15):5607–5619

    CAS  PubMed  Google Scholar 

  42. Pang KC, Frith MC, Mattick JS (2006) Rapid evolution of noncoding RNAs: lack of conservation does not mean lack of function. Trends Genet 22(1):1–5

    Article  CAS  PubMed  Google Scholar 

  43. Lewitus E, Huttner WB (2015) Neurodevelopmental LincRNA Microsyteny conservation and mammalian brain size evolution. PLoS One 10(7):e0131818

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Kelava I, Reillo I, Murayama AY, Kalinka AT, Stenzel D, Tomancak P, Matsuzaki F, Lebrand C, Sasaki E, Schwamborn JC, Okano H, Huttner WB, Borrell V (2012) Abundant occurrence of basal radial glia in the subventricular zone of embryonic neocortex of a lissencephalic primate, the common marmoset Callithrix jacchus. Cereb Cortex (New York, NY: 1991) 22(2):469–481

    Google Scholar 

  45. Kelava I, Lewitus E, Huttner WB (2013) The secondary loss of gyrencephaly as an example of evolutionary phenotypical reversal. Front Neuroanat 7:16

    Article  PubMed  PubMed Central  Google Scholar 

  46. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y, FANTOM Consortium & RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group) (2005) The transcriptional landscape of the mammalian genome. Science (New York, NY) 309(5740):1559–1563

    Article  CAS  Google Scholar 

  47. Xie C, Yuan J, Li H, Li M, Zhao G, Bu D, Zhu W, Wu W, Chen R, Zhao Y (2014) NONCODEv4: exploring the world of long non-coding RNA genes. Nucleic Acids Res 42:D98–103

    Article  CAS  PubMed  Google Scholar 

  48. Lv J, Liu H, Huang Z, Su J, He H, Xiu Y, Zhang Y, Wu Q (2013) Long non-coding RNA identification over mouse brain development by integrative modeling of chromatin and genomic features. Nucleic Acids Res 41(22):10044–10061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Blackshaw S, Harpavat S, Trimarchi J, Cai L, Huang H, Kuo WP, Weber G, Lee K, Fraioli RE, Cho SH, Yung R, Asch E, Ohno-Machado L, Wong WH, Cepko CL (2004) Genomic analysis of mouse retinal development. PLoS Biol 2(9):E247

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Aprea J, Prenninger S, Dori M, Ghosh T, Monasor LS, Wessendorf E, Zocher S, Massalini S, Alexopoulou D, Lesche M, Dahl A, Groszer M, Hiller M, Calegari F (2013) Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment. EMBO J 32(24):3145–3160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mehler MF, Mattick JS (2007) Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiol Rev 87(3):799–823

    Article  CAS  PubMed  Google Scholar 

  52. Cabili MN, Trapnell C, Goff L, Koziol M, Tazon-Vega B, Regev A, Rinn JL (2011) Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes Dev 25(18):1915–1927

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Jorgenson LA, Newsome WT, Anderson DJ, Bargmann CI, Brown EN, Deisseroth K, Donoghue JP, Hudson KL, Ling GS, MacLeish PR, Marder E, Normann RA, Sanes JR, Schnitzer MJ, Sejnowski TJ, Tank DW, Tsien RY, Ugurbil K, Wingfield JC (2015) The BRAIN initiative: developing technology to catalyse neuroscience discovery. Philos Trans R Soc Lond Ser B Biol Sci 370(1668). doi:10.1098/rstb.2014.0164

  54. Zhang K, Huang K, Luo Y, Li S (2014) Identification and functional analysis of long non-coding RNAs in mouse cleavage stage embryonic development based on single cell transcriptome data. BMC Genomics 15:845. doi:10.1186/1471-2164-15-845

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF, Sharpless NE (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA (New York, NY) 19(2):141–157

    Article  CAS  Google Scholar 

  56. Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO (2012) Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One 7(2):e30733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Barrett SP, Salzman J (2016) Circular RNAs: analysis, expression and potential functions. Development 143(11):1838–1847

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333–338

    Article  CAS  PubMed  Google Scholar 

  59. Bussotti G, Leonardi T, Clark MB, Mercer TR, Crawford J, Malquori L, Notredame C, Dinger ME, Mattick JS, Enright AJ (2016) Improved definition of the mouse transcriptome via targeted RNA sequencing. Genome Res 26(5):705–716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mercer TR, Gerhardt DJ, Dinger ME, Crawford J, Trapnell C, Jeddeloh JA, Mattick JS, Rinn JL (2011) Targeted RNA sequencing reveals the deep complexity of the human transcriptome. Nat Biotechnol 30(1):99–104

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Clark MB, Mercer TR, Bussotti G, Leonardi T, Haynes KR, Crawford J, Brunck ME, Cao KA, Thomas GP, Chen WY, Taft RJ, Nielsen LK, Enright AJ, Mattick JS, Dinger ME (2015) Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing. Nat Methods 12(4):339–342

    Article  CAS  PubMed  Google Scholar 

  62. Mercer TR, Clark MB, Crawford J, Brunck ME, Gerhardt DJ, Taft RJ, Nielsen LK, Dinger ME, Mattick JS (2014) Targeted sequencing for gene discovery and quantification using RNA Capture-Seq. Nat Protoc 9(5):989–1009

    Article  CAS  PubMed  Google Scholar 

  63. Dinger ME, Amaral PP, Mercer TR, Pang KC, Bruce SJ, Gardiner BB, Askarian-Amiri ME, Ru K, Solda G, Simons C, Sunkin SM, Crowe ML, Grimmond SM, Perkins AC, Mattick JS (2008) Long noncoding RNAs in mouse embryonic stem cell pluripotency and differentiation. Genome Res 18(9):1433–1445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bruce SJ, Gardiner BB, Burke LJ, Gongora MM, Grimmond SM, Perkins AC (2007) Dynamic transcription programs during ES cell differentiation towards mesoderm in serum versus serum-freeBMP4 culture. BMC Genomics 8:365

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR (2002) A stem cell molecular signature. Science (New York, NY) 298(5593):601–604

    Article  CAS  Google Scholar 

  66. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) "Stemness": transcriptional profiling of embryonic and adult stem cells. Science (New York, NY) 298(5593):597–600

    Article  CAS  Google Scholar 

  67. Meshorer E, Yellajoshula D, George E, Scambler PJ, Brown DT, Misteli T (2006) Hyperdynamic plasticity of chromatin proteins in pluripotent embryonic stem cells. Dev Cell 10(1):105–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Meshorer E, Misteli T (2006) Chromatin in pluripotent embryonic stem cells and differentiation. Nat Rev Mol Cell Biol 7(7):540–546

    Article  CAS  PubMed  Google Scholar 

  69. Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, Ramalho-Santos M (2009) Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature 460(7257):863–868

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES (2009) Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458(7235):223–227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Guttman M, Garber M, Levin JZ, Donaghey J, Robinson J, Adiconis X, Fan L, Koziol MJ, Gnirke A, Nusbaum C, Rinn JL, Lander ES, Regev A (2010) Ab initio reconstruction of cell type-specific transcriptomes in mouse reveals the conserved multi-exonic structure of lincRNAs. Nat Biotechnol 28(5):503–510

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mercer TR, Qureshi IA, Gokhan S, Dinger ME, Li G, Mattick JS, Mehler MF (2010) Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation. BMC Neurosci 11:14. doi:10.1186/1471-2202-11-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T (2002) Identification of tissue-specific microRNAs from mouse. Curr Biol 12(9):735–739

    Article  CAS  PubMed  Google Scholar 

  74. Makeyev EV, Zhang J, Carrasco MA, Maniatis T (2007) The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. Mol Cell 27(3):435–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Ng SY, Johnson R, Stanton LW (2012) Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J 31(3):522–533

    Article  CAS  PubMed  Google Scholar 

  76. Guo Y, Zhang P, Sheng Q, Zhao S, Hackett TA (2016) lncRNA expression in the auditory forebrain during postnatal development. Gene 593(1):201–216

    Article  CAS  PubMed  Google Scholar 

  77. Ramos AD, Diaz A, Nellore A, Delgado RN, Park KY, Gonzales-Roybal G, Oldham MC, Song JS, Lim DA (2013) Integration of genome-wide approaches identifies lncRNAs of adult neural stem cells and their progeny in vivo. Cell Stem Cell 12(5):616–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Liu SJ, Nowakowski TJ, Pollen AA, Lui JH, Horlbeck MA, Attenello FJ, He D, Weissman JS, Kriegstein AR, Diaz AA, Lim DA (2016) Single-cell analysis of long non-coding RNAs in the developing human neocortex. Genome Biol 17:67. doi:10.1186/s13059-016-0932-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Rapicavoli NA, Blackshaw S (2009) New meaning in the message: noncoding RNAs and their role in retinal development. Dev Dyn 238(9):2103–2114

    Article  CAS  PubMed  Google Scholar 

  80. Molyneaux BJ, Goff LA, Brettler AC, Chen HH, Brown JR, Hrvatin S, Rinn JL, Arlotta P (2015) DeCoN: genome-wide analysis of in vivo transcriptional dynamics during pyramidal neuron fate selection in neocortex. Neuron 85(2):275–288

    Article  CAS  PubMed  Google Scholar 

  81. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, Boe AF, Boguski MS, Brockway KS, Byrnes EJ, Chen L, Chen L, Chen TM, Chin MC, Chong J, Crook BE, Czaplinska A, Dang CN, Datta S, Dee NR, Desaki AL, Desta T, Diep E, Dolbeare TA, Donelan MJ, Dong HW, Dougherty JG, Duncan BJ, Ebbert AJ, Eichele G, Estin LK, Faber C, Facer BA, Fields R, Fischer SR, Fliss TP, Frensley C, Gates SN, Glattfelder KJ, Halverson KR, Hart MR, Hohmann JG, Howell MP, Jeung DP, Johnson RA, Karr PT, Kawal R, Kidney JM, Knapik RH, Kuan CL, Lake JH, Laramee AR, Larsen KD, Lau C, Lemon TA, Liang AJ, Liu Y, Luong LT, Michaels J, Morgan JJ, Morgan RJ, Mortrud MT, Mosqueda NF, Ng LL, Ng R, Orta GJ, Overly CC, Pak TH, Parry SE, Pathak SD, Pearson OC, Puchalski RB, Riley ZL, Rockett HR, Rowland SA, Royall JJ, Ruiz MJ, Sarno NR, Schaffnit K, Shapovalova NV, Sivisay T, Slaughterbeck CR, Smith SC, Smith KA, Smith BI, Sodt AJ, Stewart NN, Stumpf KR, Sunkin SM, Sutram M, Tam A, Teemer CD, Thaller C, Thompson CL, Varnam LR, Visel A, Whitlock RM, Wohnoutka PE, Wolkey CK, Wong VY, Wood M, Yaylaoglu MB, Young RC, Youngstrom BL, Yuan XF, Zhang B, Zwingman TA, Jones AR (2007) Genome-wide atlas of gene expression in the adult mouse brain. Nature 445(7124):168–176

    Article  CAS  PubMed  Google Scholar 

  82. Kour S, Rath PC (2015) Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain. Int J Dev Neurosci 47(Pt B):286–297

    Article  CAS  PubMed  Google Scholar 

  83. Mills JD, Chen J, Kim WS, Waters PD, Prabowo AS, Aronica E, Halliday GM, Janitz M (2015) Long intervening non-coding RNA 00320 is human brain-specific and highly expressed in the cortical white matter. Neurogenetics 16(3):201–213

    Article  CAS  PubMed  Google Scholar 

  84. Dietz WH, Masterson K, Sittig LJ, Redei EE, Herzing LB (2012) Imprinting and expression of Dio3os mirrors Dio3 in rat. Front Genet 3:279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kohtz JD, Baker DP, Corte G, Fishell G (1998) Regionalization within the mammalian telencephalon is mediated by changes in responsiveness to sonic hedgehog. Development 125(24):5079–5089

    CAS  PubMed  Google Scholar 

  86. Kohtz JD, Fishell G (2004) Developmental regulation of EVF-1, a novel non-coding RNA transcribed upstream of the mouse Dlx6 gene. Gene Expr Patterns 4(4):407–412

    Article  CAS  PubMed  Google Scholar 

  87. Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD (2006) The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes Dev 20(11):1470–1484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Davis CJ, Taishi P, Honn KA, Koberstein JN, Krueger JM (2016) P2X7 receptors in body temperature, locomotor activity, and brain mRNA and lncRNA responses to sleep deprivation. Am J Physiol Regul Integr Comp Physiol 311(6):R1004–R1012. doi:10.1152/ajpregu.00167.2016

    Article  PubMed  Google Scholar 

  89. Zhong J, Jiang L, Cheng C, Huang Z, Zhang H, Liu H, He J, Cao F, Peng J, Jiang Y, Sun X (2016) Altered expression of long non-coding RNA and mRNA in mouse cortex after traumatic brain injury. Brain Res 1646:589–600

    Article  CAS  PubMed  Google Scholar 

  90. Jiang H, Good DJ (2016) A molecular conundrum involving hypothalamic responses to and roles of long non-coding RNAs following food deprivation. Mol Cell Endocrinol 438:52–60

    Article  CAS  PubMed  Google Scholar 

  91. D’haene E, Jacobs EZ, Volders PJ, De Meyer T, Menten B, Vergult S (2016) Identification of long non-coding RNAs involved in neuronal development and intellectual disability. Sci Rep 6:28396

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Chen R, Liu L, Xiao M, Wang F, Lin X (2016) Microarray expression profile analysis of long noncoding RNAs in premature brain injury: a novel point of view. Neuroscience 319:123–133

    Article  CAS  PubMed  Google Scholar 

  93. Kraus TF, Haider M, Spanner J, Steinmaurer M, Dietinger V, Kretzschmar HA (2016) Altered long noncoding RNA expression precedes the course of Parkinson’s disease-a preliminary report. Mol Neurobiol 54(4):2869–2877

    Article  PubMed  CAS  Google Scholar 

  94. Faedo A, Quinn JC, Stoney P, Long JE, Dye C, Zollo M, Rubenstein JL, Price DJ, Bulfone A (2004) Identification and characterization of a novel transcript down-regulated in Dlx1/Dlx2 and up-regulated in Pax6 mutant telencephalon. Dev Dyn 231(3):614–620

    Article  CAS  PubMed  Google Scholar 

  95. Kour S, Rath PC (2016) All-trans retinoic acid induces expression of a novel Intergenic long noncoding RNA in adult rat primary hippocampal neurons. J Mol Neurosci 58(2):266–276

    Article  CAS  PubMed  Google Scholar 

  96. Chen X, Zhou X, Lu D, Yang X, Zhou Z, Chen X, Chen Y, He W, Feng X (2016) Aberrantly expressed long noncoding RNAs are involved in sevoflurane-induced developing hippocampal neuronal apoptosis: a microarray related study. Metab Brain Dis 31(5):1031–1040

    Article  CAS  PubMed  Google Scholar 

  97. Clark BS, Blackshaw S (2014) Long non-coding RNA-dependent transcriptional regulation in neuronal development and disease. Front Genet 5:164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Guttman M, Donaghey J, Carey BW, Garber M, Grenier JK, Munson G, Young G, Lucas AB, Ach R, Bruhn L, Yang X, Amit I, Meissner A, Regev A, Rinn JL, Root DE, Lander ES (2011) lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477(7364):295–300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Wang C, Li G, Wu Y, Xi J, Kang J (2016) LincRNA1230 inhibits the differentiation of mouse ES cells towards neural progenitors. Sci China Life Sci 59(5):443–454

    Article  CAS  PubMed  Google Scholar 

  100. Lin N, Chang KY, Li Z, Gates K, Rana ZA, Dang J, Zhang D, Han T, Yang CS, Cunningham TJ, Head SR, Duester G, Dong PD, Rana TM (2014) An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. Mol Cell 53(6):1005–1019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Chu C, Qu K, Zhong FL, Artandi SE, Chang HY (2011) Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell 44(4):667–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ng SY, Bogu GK, Soh BS, Stanton LW (2013) The long noncoding RNA RMST interacts with SOX2 to regulate neurogenesis. Mol Cell 51(3):349–359

    Article  CAS  PubMed  Google Scholar 

  103. Anderegg A, Lin HP, Chen JA, Caronia-Brown G, Cherepanova N, Yun B, Joksimovic M, Rock J, Harfe BD, Johnson R, Awatramani R (2013) An Lmx1b-miR135a2 regulatory circuit modulates Wnt1/Wnt signaling and determines the size of the midbrain dopaminergic progenitor pool. PLoS Genet 9(12):e1003973

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Anderegg A, Awatramani R (2015) k the size of the midbrain and the dopaminergic progenitor pool. Neurogenesis (Austin, TX) 2(1):e998101

    Article  Google Scholar 

  105. Caronia-Brown G, Anderegg A, Awatramani R (2016) Expression and functional analysis of the Wnt/beta-catenin induced mir-135a-2 locus in embryonic forebrain development. Neural Dev 11:9. doi:10.1186/s13064-016-0065-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Tochitani S, Hayashizaki Y (2008) Nkx2.2 antisense RNA overexpression enhanced oligodendrocytic differentiation. Biochem Biophys Res Commun 372(4):691–696

    Article  CAS  PubMed  Google Scholar 

  107. Qi Y, Cai J, Wu Y, Wu R, Lee J, Fu H, Rao M, Sussel L, Rubenstein J, Qiu M (2001) Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development 128(14):2723–2733

    CAS  PubMed  Google Scholar 

  108. Dong X, Chen K, Cuevas-Diaz Duran R, You Y, Sloan SA, Zhang Y, Zong S, Cao Q, Barres BA, Wu JQ (2015) Comprehensive identification of long non-coding RNAs in purified cell types from the brain reveals functional LncRNA in OPC fate determination. PLoS Genet 11(12):e1005669

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Yang N, Zuchero JB, Ahlenius H, Marro S, Ng YH, Vierbuchen T, Hawkins JS, Geissler R, Barres BA, Wernig M (2013) Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol 31(5):434–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Lu QR, Sun T, Zhu Z, Ma N, Garcia M, Stiles CD, Rowitch DH (2002) Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell 109(1):75–86

    Article  CAS  PubMed  Google Scholar 

  111. Zhou Q, Choi G, Anderson DJ (2001) The bHLH transcription factor Olig2 promotes oligodendrocyte differentiation in collaboration with Nkx2.2. Neuron 31(5):791–807

    Article  CAS  PubMed  Google Scholar 

  112. Rani N, Nowakowski TJ, Zhou H, Godshalk SE, Lisi V, Kriegstein AR, Kosik KS (2016) A primate lncRNA mediates notch signaling during neuronal development by sequestering miRNA. Neuron 90(6):1174–1188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A, Bozzoni I (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147(2):358–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Ebert MS, Sharp PA (2010) Emerging roles for natural microRNA sponges. Curr Biol 20(19):R858–R861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Hansen TB, Kjems J, Damgaard CK (2013) Circular RNA and miR-7 in cancer. Cancer Res 73(18):5609–5612

    Article  CAS  PubMed  Google Scholar 

  116. Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, Lu L, Liu C, Yi JS, Zhang H, Min W, Bennett AM, Gregory RI, Ding Y, Huang Y (2013) The imprinted H19 lncRNA antagonizes let-7 microRNAs. Mol Cell 52(1):101–112

    Article  CAS  PubMed  Google Scholar 

  117. Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F, Lieberman J, Rigoutsos I, Pandolfi PP (2011) Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 147(2):344–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505(7483):344–352

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Wang Y, Xu Z, Jiang J, Xu C, Kang J, Xiao L, Wu M, Xiong J, Guo X, Liu H (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25(1):69–80

    Article  CAS  PubMed  Google Scholar 

  120. Zhang Z, Zhu Z, Watabe K, Zhang X, Bai C, Xu M, Wu F, Mo YY (2013) Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ 20(11):1558–1568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Bail S, Swerdel M, Liu H, Jiao X, Goff LA, Hart RP, Kiledjian M (2010) Differential regulation of microRNA stability. RNA (New York, NY) 16(5):1032–1039

    Article  CAS  Google Scholar 

  122. Legnini I, Morlando M, Mangiavacchi A, Fatica A, Bozzoni I (2014) A feedforward regulatory loop between HuR and the long noncoding RNA linc-MD1 controls early phases of myogenesis. Mol Cell 53(3):506–514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Stevens SJ, van Ravenswaaij-Arts CM, Janssen JW, Klein Wassink-Ruiter JS, van Essen AJ, Dijkhuizen T, van Rheenen J, Heuts-Vijgen R, Stegmann AP, Smeets EE, Engelen JJ (2011) MYT1L is a candidate gene for intellectual disability in patients with 2p25.3 (2pter) deletions. Am J Med Genet A 155A(11):2739–2745

    Article  PubMed  CAS  Google Scholar 

  124. Rio M, Royer G, Gobin S, de Blois MC, Ozilou C, Bernheim A, Nizon M, Munnich A, Bonnefont JP, Romana S, Vekemans M, Turleau C, Malan V (2013) Monozygotic twins discordant for submicroscopic chromosomal anomalies in 2p25.3 region detected by array CGH. Clin Genet 84(1):31–36

    Article  CAS  PubMed  Google Scholar 

  125. Doco-Fenzy M, Leroy C, Schneider A, Petit F, Delrue MA, Andrieux J, Perrin-Sabourin L, Landais E, Aboura A, Puechberty J, Girard M, Tournaire M, Sanchez E, Rooryck C, Ameil A, Goossens M, Jonveaux P, Lefort G, Taine L, Cailley D, Gaillard D, Leheup B, Sarda P, Genevieve D (2014) Early-onset obesity and paternal 2pter deletion encompassing the ACP1, TMEM18, and MYT1L genes. Eur J Hum Genet 22(4):471–479

    Article  CAS  PubMed  Google Scholar 

  126. Bonaglia MC, Giorda R, Zanini S (2014) A new patient with a terminal de novo 2p25.3 deletion of 1.9 Mb associated with early-onset of obesity, intellectual disabilities and hyperkinetic disorder. Mol Cytogenet 7:53. doi:10.1186/1755-8166-7-53

    Article  PubMed  PubMed Central  Google Scholar 

  127. Gaiano N, Nye JS, Fishell G (2000) Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron 26(2):395–404

    Article  CAS  PubMed  Google Scholar 

  128. Shimojo H, Ohtsuka T, Kageyama R (2008) Oscillations in notch signaling regulate maintenance of neural progenitors. Neuron 58(1):52–64

    Article  CAS  PubMed  Google Scholar 

  129. Yoon KJ, Koo BK, Im SK, Jeong HW, Ghim J, Kwon MC, Moon JS, Miyata T, Kong YY (2008) Mind bomb 1-expressing intermediate progenitors generate notch signaling to maintain radial glial cells. Neuron 58(4):519–531

    Article  CAS  PubMed  Google Scholar 

  130. Gordon FE, Nutt CL, Cheunsuchon P, Nakayama Y, Provencher KA, Rice KA, Zhou Y, Zhang X, Klibanski A (2010) Increased expression of angiogenic genes in the brains of mouse meg3-null embryos. Endocrinology 151(6):2443–2452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Sun S, Payer B, Namekawa S, An JY, Press W, Catalan-Dibene J, Sunwoo H, Lee JT (2015) Xist imprinting is promoted by the hemizygous (unpaired) state in the male germ line. Proc Natl Acad Sci U S A 112(47):14415–14422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Alfano G, Vitiello C, Caccioppoli C, Caramico T, Carola A, Szego MJ, McInnes RR, Auricchio A, Banfi S (2005) Natural antisense transcripts associated with genes involved in eye development. Hum Mol Genet 14(7):913–923

    Article  CAS  PubMed  Google Scholar 

  133. Young TL, Matsuda T, Cepko CL (2005) The noncoding RNA taurine upregulated gene 1 is required for differentiation of the murine retina. Curr Biol 15(6):501–512

    Article  CAS  PubMed  Google Scholar 

  134. Krol J, Krol I, Alvarez CP, Fiscella M, Hierlemann A, Roska B, Filipowicz W (2015) A network comprising short and long noncoding RNAs and RNA helicase controls mouse retina architecture. Nat Commun 6:7305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Rapicavoli NA, Poth EM, Blackshaw S (2010) The long noncoding RNA RNCR2 directs mouse retinal cell specification. BMC Dev Biol 10:49. doi:10.1186/1471-213X-10-49

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Rapicavoli NA, Poth EM, Zhu H, Blackshaw S (2011) The long noncoding RNA Six3OS acts in trans to regulate retinal development by modulating Six3 activity. Neural Dev 6:32. doi:10.1186/1749-8104-6-32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Khalil AM, Guttman M, Huarte M, Garber M, Raj A, Rivea Morales D, Thomas K, Presser A, Bernstein BE, van Oudenaarden A, Regev A, Lander ES, Rinn JL (2009) Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106(28):11667–11672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Ishii N, Ozaki K, Sato H, Mizuno H, Saito S, Takahashi A, Miyamoto Y, Ikegawa S, Kamatani N, Hori M, Saito S, Nakamura Y, Tanaka T (2006) Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction. J Hum Genet 51(12):1087–1099

    Article  CAS  PubMed  Google Scholar 

  139. Sone M, Hayashi T, Tarui H, Agata K, Takeichi M, Nakagawa S (2007) The mRNA-like noncoding RNA Gomafu constitutes a novel nuclear domain in a subset of neurons. J Cell Sci 120(Pt 15):2498–2506

    Article  CAS  PubMed  Google Scholar 

  140. Barry G, Briggs JA, Vanichkina DP, Poth EM, Beveridge NJ, Ratnu VS, Nayler SP, Nones K, Hu J, Bredy TW, Nakagawa S, Rigo F, Taft RJ, Cairns MJ, Blackshaw S, Wolvetang EJ, Mattick JS (2014) The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing. Mol Psychiatry 19(4):486–494

    Article  CAS  PubMed  Google Scholar 

  141. Zhao J, Ohsumi TK, Kung JT, Ogawa Y, Grau DJ, Sarma K, Song JJ, Kingston RE, Borowsky M, Lee JT (2010) Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell 40(6):939–953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Meola N, Pizzo M, Alfano G, Surace EM, Banfi S (2012) The long noncoding RNA Vax2os1 controls the cell cycle progression of photoreceptor progenitors in the mouse retina. RNA (New York, NY) 18(1):111–123

    Article  CAS  Google Scholar 

  143. Ramos AD, Andersen RE, Liu SJ, Nowakowski TJ, Hong SJ, Gertz CC, Salinas RD, Zarabi H, Kriegstein AR, Lim DA (2015) The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells. Cell Stem Cell 16(4):439–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Kriegstein A, Alvarez-Buylla A (2009) The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci 32:149–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Zheng S, Gray EE, Chawla G, Porse BT, O’Dell TJ, Black DL (2012) PSD-95 is post-transcriptionally repressed during early neural development by PTBP1 and PTBP2. Nat Neurosci 15(3):381–388, S1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Yap K, Lim ZQ, Khandelia P, Friedman B, Makeyev EV (2012) Coordinated regulation of neuronal mRNA steady-state levels through developmentally controlled intron retention. Genes Dev 26(11):1209–1223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Keppetipola N, Sharma S, Li Q, Black DL (2012) Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit Rev Biochem Mol Biol 47(4):360–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Shibasaki T, Tokunaga A, Sakamoto R, Sagara H, Noguchi S, Sasaoka T, Yoshida N (2013) PTB deficiency causes the loss of adherens junctions in the dorsal telencephalon and leads to lethal hydrocephalus. Cereb Cortex (New York, NY: 1991) 23(8):1824–1835

    Google Scholar 

  149. Boutz PL, Stoilov P, Li Q, Lin CH, Chawla G, Ostrow K, Shiue L, Ares M Jr, Black DL (2007) A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons. Genes Dev 21(13):1636–1652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Licatalosi DD, Yano M, Fak JJ, Mele A, Grabinski SE, Zhang C, Darnell RB (2012) Ptbp2 represses adult-specific splicing to regulate the generation of neuronal precursors in the embryonic brain. Genes Dev 26(14):1626–1642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Bond AM, Vangompel MJ, Sametsky EA, Clark MF, Savage JC, Disterhoft JF, Kohtz JD (2009) Balanced gene regulation by an embryonic brain ncRNA is critical for adult hippocampal GABA circuitry. Nat Neurosci 12(8):1020–1027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Berghoff EG, Clark MF, Chen S, Cajigas I, Leib DE, Kohtz JD (2013) Evf2 (Dlx6as) lncRNA regulates ultraconserved enhancer methylation and the differential transcriptional control of adjacent genes. Development 140(21):4407–4416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Cajigas I, Leib DE, Cochrane J, Luo H, Swyter KR, Chen S, Clark BS, Thompson J, Yates JR 3rd, Kingston RE, Kohtz JD (2015) Evf2 lncRNA/BRG1/DLX1 interactions reveal RNA-dependent inhibition of chromatin remodeling. Development 142(15):2641–2652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Kraus P, Sivakamasundari V, Lim SL, Xing X, Lipovich L, Lufkin T (2013) Making sense of Dlx1 antisense RNA. Dev Biol 376(2):224–235

    Article  CAS  PubMed  Google Scholar 

  155. Cobos I, Calcagnotto ME, Vilaythong AJ, Thwin MT, Noebels JL, Baraban SC, Rubenstein JL (2005) Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nat Neurosci 8(8):1059–1068

    Article  CAS  PubMed  Google Scholar 

  156. Jones DL, Howard MA, Stanco A, Rubenstein JL, Baraban SC (2011) Deletion of Dlx1 results in reduced glutamatergic input to hippocampal interneurons. J Neurophysiol 105(5):1984–1991

    Article  PubMed  PubMed Central  Google Scholar 

  157. Petryniak MA, Potter GB, Rowitch DH, Rubenstein JL (2007) Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain. Neuron 55(3):417–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108(2):193–199

    Article  CAS  PubMed  Google Scholar 

  159. Stuhmer T, Anderson SA, Ekker M, Rubenstein JL (2002) Ectopic expression of the Dlx genes induces glutamic acid decarboxylase and Dlx expression. Development 129(1):245–252

    CAS  PubMed  Google Scholar 

  160. Sauvageau M, Goff LA, Lodato S, Bonev B, Groff AF, Gerhardinger C, Sanchez-Gomez DB, Hacisuleyman E, Li E, Spence M, Liapis SC, Mallard W, Morse M, Swerdel MR, D’Ecclessis MF, Moore JC, Lai V, Gong G, Yancopoulos GD, Frendewey D, Kellis M, Hart RP, Valenzuela DM, Arlotta P, Rinn JL (2013) Multiple knockout mouse models reveal lincRNAs are required for life and brain development. elife 2:e01749

    Article  PubMed  PubMed Central  Google Scholar 

  161. Grote P, Herrmann BG (2013) The long non-coding RNA Fendrr links epigenetic control mechanisms to gene regulatory networks in mammalian embryogenesis. RNA Biol 10(10):1579–1585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Grote P, Wittler L, Hendrix D, Koch F, Wahrisch S, Beisaw A, Macura K, Blass G, Kellis M, Werber M, Herrmann BG (2013) The tissue-specific lncRNA Fendrr is an essential regulator of heart and body wall development in the mouse. Dev Cell 24(2):206–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. McEvilly RJ, de Diaz MO, Schonemann MD, Hooshmand F, Rosenfeld MG (2002) Transcriptional regulation of cortical neuron migration by POU domain factors. Science (New York, NY) 295(5559):1528–1532

    Article  CAS  Google Scholar 

  164. Sugitani Y, Nakai S, Minowa O, Nishi M, Jishage K, Kawano H, Mori K, Ogawa M, Noda T (2002) Brn-1 and Brn-2 share crucial roles in the production and positioning of mouse neocortical neurons. Genes Dev 16(14):1760–1765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Dominguez MH, Ayoub AE, Rakic P (2013) POU-III transcription factors (Brn1, Brn2, and Oct6) influence neurogenesis, molecular identity, and migratory destination of upper-layer cells of the cerebral cortex. Cereb Cortex (New York, NY: 1991) 23(11):2632–2643

    Google Scholar 

  166. Goff LA, Groff AF, Sauvageau M, Trayes-Gibson Z, Sanchez-Gomez DB, Morse M, Martin RD, Elcavage LE, Liapis SC, Gonzalez-Celeiro M, Plana O, Li E, Gerhardinger C, Tomassy GS, Arlotta P, Rinn JL (2015) Spatiotemporal expression and transcriptional perturbations by long noncoding RNAs in the mouse brain. Proc Natl Acad Sci U S A 112(22):6855–6862

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Eissmann M, Gutschner T, Hammerle M, Gunther S, Caudron-Herger M, Gross M, Schirmacher P, Rippe K, Braun T, Zornig M, Diederichs S (2012) Loss of the abundant nuclear non-coding RNA MALAT1 is compatible with life and development. RNA Biol 9(8):1076–1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Nakagawa S, Ip JY, Shioi G, Tripathi V, Zong X, Hirose T, Prasanth KV (2012) Malat1 is not an essential component of nuclear speckles in mice. RNA (New York, NY) 18(8):1487–1499

    Article  CAS  Google Scholar 

  169. Zhang B, Arun G, Mao YS, Lazar Z, Hung G, Bhattacharjee G, Xiao X, Booth CJ, Wu J, Zhang C, Spector DL (2012) The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep 2(1):111–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Oliver PL, Chodroff RA, Gosal A, Edwards B, Cheung AF, Gomez-Rodriguez J, Elliot G, Garrett LJ, Lickiss T, Szele F, Green ED, Molnar Z, Ponting CP (2015) Disruption of Visc-2, a brain-expressed conserved long noncoding RNA, does not elicit an overt anatomical or behavioral phenotype. Cereb cortex (New York, NY: 1991) 25(10):3572–3585

    Google Scholar 

  171. Sunwoo H, Dinger ME, Wilusz JE, Amaral PP, Mattick JS, Spector DL (2009) MEN epsilon/beta nuclear-retained non-coding RNAs are up-regulated upon muscle differentiation and are essential components of paraspeckles. Genome Res 19(3):347–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Sasaki YT, Ideue T, Sano M, Mituyama T, Hirose T (2009) MENepsilon/beta noncoding RNAs are essential for structural integrity of nuclear paraspeckles. Proc Natl Acad Sci U S A 106(8):2525–2530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Clemson CM, Hutchinson JN, Sara SA, Ensminger AW, Fox AH, Chess A, Lawrence JB (2009) An architectural role for a nuclear noncoding RNA: NEAT1 RNA is essential for the structure of paraspeckles. Mol Cell 33(6):717–726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Fox AH, Bond CS, Lamond AI (2005) P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner. Mol Biol Cell 16(11):5304–5315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Chen LL, Carmichael GG (2009) Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA. Mol Cell 35(4):467–478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Nakagawa S, Naganuma T, Shioi G, Hirose T (2011) Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice. J Cell Biol 193(1):31–39

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Nakagawa S, Shimada M, Yanaka K, Mito M, Arai T, Takahashi E, Fujita Y, Fujimori T, Standaert L, Marine JC, Hirose T (2014) The lncRNA Neat1 is required for corpus luteum formation and the establishment of pregnancy in a subpopulation of mice. Development 141(23):4618–4627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. West JA, Mito M, Kurosaka S, Takumi T, Tanegashima C, Chujo T, Yanaka K, Kingston RE, Hirose T, Bond C, Fox A, Nakagawa S (2016) Structural, super-resolution microscopy analysis of paraspeckle nuclear body organization. J Cell Biol 214(7):817–830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Nishimoto Y, Nakagawa S, Hirose T, Okano HJ, Takao M, Shibata S, Suyama S, Kuwako K, Imai T, Murayama S, Suzuki N, Okano H (2013) The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis. Mol Brain 6:31. doi:10.1186/1756-6606-6-31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Ip JY, Sone M, Nashiki C, Pan Q, Kitaichi K, Yanaka K, Abe T, Takao K, Miyakawa T, Blencowe BJ, Nakagawa S (2016) Gomafu lncRNA knockout mice exhibit mild hyperactivity with enhanced responsiveness to the psychostimulant methamphetamine. Sci Rep 6:27204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Tsuiji H, Yoshimoto R, Hasegawa Y, Furuno M, Yoshida M, Nakagawa S (2011) Competition between a noncoding exon and introns: Gomafu contains tandem UACUAAC repeats and associates with splicing factor-1. Genes Cells 16(5):479–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Ishizuka A, Hasegawa Y, Ishida K, Yanaka K, Nakagawa S (2014) Formation of nuclear bodies by the lncRNA Gomafu-associating proteins Celf3 and SF1. Genes Cells 19(9):704–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

B.S.C. was supported by F32EY024201 from the NIH.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Seth Blackshaw Ph.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Clark, B.S., Blackshaw, S. (2017). Understanding the Role of lncRNAs in Nervous System Development. In: Rao, M. (eds) Long Non Coding RNA Biology. Advances in Experimental Medicine and Biology, vol 1008. Springer, Singapore. https://doi.org/10.1007/978-981-10-5203-3_9

Download citation

Publish with us

Policies and ethics