Skip to main content
SpringerLink
Log in

Development and differentiation of neural rosettes derived from human embryonic stem cells

  • Original Article
  • Published:
Stem Cell Reviews Aims and scope Submit manuscript

Abstract

Neurons and glia are important targets of human embryonic stem cell research promising a renewable source of these differentiated cells for biomedical research and regenerative medicine. Neurons and glia are derived, in vivo from the neuroepithelium of the neural tube. Concomitant to development along the anterior to posterior axis, gradients of morphogens across the dorsal and ventral axis of the neural tube establish positional codes that generate distinct progenitor domains and ultimately specify subtype identity. The neural rosette is the developmental signature of neuroprogenitors in cultures of differentiating embryonic stem cells; rosettes are radial arrangements of columnar cells that express many of the proteins expressed in neuroepithelial cells in the neural tube. In addition to similar morphology, neuroprogenitors within neural rosettes differentiate into the main classes of progeny of neuroepithelial cells in vivo: neurons, oligodendrocytes, and astrocytes. Despite these similarities, important differences exist and the extent to which neural rosettes can model neurogenesis in vivo is not yet clear. Here, the authors review the recent studies on the development and differentiation of neural rosettes from human embryonic stem cells. The authors focus on efforts to generate motor neurons and oligodendrocytes in vitro as representative of the challenges to obtaining the progeny of a single progenitor domain with in vitro methods. Opportunities for further progress are discussed.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Thomson JA, Itskovitz-Eldor J, Shapiro SS, et al. Scence 1998; 282:1145–1147.

    CAS  Google Scholar 

  2. Ji RR, Stichartz G. Sci STEK 2004;2004:reE14.

    Google Scholar 

  3. Miller G. Science 2005;308:778–781.

    Article  PubMed  CAS  Google Scholar 

  4. Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. Nat Biotechnol 2000;18:399–404.

    Article  PubMed  CAS  Google Scholar 

  5. Reubinoff BE, Itsykson P, Turetsky T, et al. Nat Biotechnol 2001; 19:1134–1140.

    Article  PubMed  CAS  Google Scholar 

  6. Carpenter MK, Inokuma MS, Denham J, Mujtaba T, Chiu CP, Rao MS. Exp Neurol 2001;172:383–397.

    Article  PubMed  CAS  Google Scholar 

  7. Itskovitz-Eldor J, Schuldiner M, Karsenti D, et al. Mol Med 2000; 6:88–95.

    PubMed  CAS  Google Scholar 

  8. Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N. Proc Natl Acad Sci USA 2000;97:11,307–11,312.

    Article  CAS  Google Scholar 

  9. Pera MF, Trounson AC. Development 2004;131:5515–5525.

    Article  PubMed  CAS  Google Scholar 

  10. Attisano L, Wrana JL. Science 2000;296:1646, 1647.

    Article  Google Scholar 

  11. Moreau M, Leclerc C. Int J Dev Biol 2004;48:75–84.

    Article  PubMed  CAS  Google Scholar 

  12. Muñoz-Sanjuán I, Brivanlou AH. Nat Rev Neurosci 2002;3.

  13. Dupont S, Zacchigan L, Cordenonsi M, et al. Cell 2005;121:87–99.

    Article  PubMed  CAS  Google Scholar 

  14. Wilson SI, Graziano E, Harland R, Jessell TM, Edlund T. Curr Biol 2000;10:421–429.

    Article  PubMed  CAS  Google Scholar 

  15. Wilson SI, Rydstrom A, Trimborn T, et al. Nature 2001;1411: 325–330.

    Article  Google Scholar 

  16. Sasai Y. Nature 2005;435:433, 434.

    Article  PubMed  CAS  Google Scholar 

  17. Detraitt ER, George TM, Etchevers HC, Gilbert JR, Vekemans M, Speer MC. Neurotoxicol Teratol 2005;27:515–524.

    Article  CAS  Google Scholar 

  18. Gotz M, Barde YA. Neuron 2005;46:369–372.

    Article  PubMed  CAS  Google Scholar 

  19. Mori T, Buffo A, Gotz M. Curr Top Dev Biol 2005;69:65–97.

    Google Scholar 

  20. Fujita S. J Comp Neurol 1964;122.

  21. Sauer FC. J Comp Neurol 1935;62.

  22. Ever L, Gaiano N. Curr Opin Neurobiol 2005;15:29–33.

    Article  PubMed  CAS  Google Scholar 

  23. Rakic P. Glia 2003;43:19–32.

    Article  PubMed  Google Scholar 

  24. Hatakeyama J, Bessho Y, Katoh K, et al. Development 2004;131:5539–5550.

    Article  PubMed  CAS  Google Scholar 

  25. Glaser T, Brustle O. Trends Neurosci 2005;28:397–400.

    Article  PubMed  CAS  Google Scholar 

  26. Le Douarin NM, Creuzet S, Couly G, Dypin E. Development 2004;131:4637–4650.

    Article  PubMed  CAS  Google Scholar 

  27. Le Douarin NM, Dupin E. Curr Opin Genet Dev 2003;13:529–536.

    Article  PubMed  CAS  Google Scholar 

  28. Grundy D, Schemann M. Curr Opin Gastroenterol 2005;21:176–182.

    Article  PubMed  Google Scholar 

  29. Anderson DJ. Philos Trans R Soc Lond B Biol Sci 2000;355:953–964.

    Article  PubMed  CAS  Google Scholar 

  30. Kawasaki H, Mizuseki K, Nishikawa S, et al. Neuron 2000;28:31–40.

    Article  PubMed  CAS  Google Scholar 

  31. Mizuseki K, Sakamoto T, Watanabe K, et al. Proc Natl Acad Sci USA 2003;100:5828–5833.

    Article  PubMed  CAS  Google Scholar 

  32. Pomp O, Brokhman I, Ben-Dor I, Reubinoff B, Goldstein RS. Stem Cell 2005;23:923–930.

    Article  CAS  Google Scholar 

  33. Briscoe J, Ericson J. Curr Opi Neurobiol 2001;11:43–49.

    Article  CAS  Google Scholar 

  34. Helms AW, Johnson JE. Curr Opin Neurobiol 2003;13:42–49.

    Article  PubMed  CAS  Google Scholar 

  35. Jessell TM. Nat Rev Genet 2000;1:20–29.

    Article  PubMed  CAS  Google Scholar 

  36. Guthrie S. Curr Biol 2002;12:R488-R490.

    Article  PubMed  CAS  Google Scholar 

  37. Guthrie S. Curr Biol 2004;14:R166-R168.

    Article  PubMed  CAS  Google Scholar 

  38. Caspary T, Anderson KV. Nat Rev Neurosci;2003;4:289–297.

    Article  PubMed  CAS  Google Scholar 

  39. Price SR, Briscoe J. Mech Dev 2004;121:1103–1115.

    Article  PubMed  CAS  Google Scholar 

  40. Chizhikov VV, Millen KJ. Dev Biol 2005;277:287–295.

    Article  PubMed  CAS  Google Scholar 

  41. Wilson L, Maden M. Dev Biol 2005;282:1–13.

    Article  PubMed  CAS  Google Scholar 

  42. Zhang J, Li L. Dev Biol 2005;284:1–11.

    Article  PubMed  CAS  Google Scholar 

  43. Jacob J, Briscoe J. EMBO Rep 2003;4:761–765.

    Article  PubMed  CAS  Google Scholar 

  44. Ericson J, Briscoe J, Rashbass P, van Heyningen V, Jessell TM. Cold Spring Harb Symp Quant Biol 1997;62:451–466.

    PubMed  CAS  Google Scholar 

  45. Stamataki D, Ulloa F, Tsoni SV, Mynett A, Briscoe J. Genes Dev 2005;19:626–641.

    Article  PubMed  CAS  Google Scholar 

  46. Appel B, Eisen JS. Neuron 2003;40:461–464.

    Article  PubMed  CAS  Google Scholar 

  47. Novitch BG, Wichterle H, Jessell TM, Sockanathan S. Neuron 2003;40:8–195.

    Article  Google Scholar 

  48. Wegner M, Stolt CC. Trends Neurosci 2005;28:583–588.

    Article  PubMed  CAS  Google Scholar 

  49. Episkopou V. Trends Neurosci 2005;28:219–221.

    Article  PubMed  CAS  Google Scholar 

  50. Graham V, Khudyakov J, Ellis P, Pevny L. Neuron 2003;39: 749–765.

    Article  PubMed  CAS  Google Scholar 

  51. Pevny LH, Lovell-Badge R. Curr Opin Genet Dev 1997;7:338–344.

    Article  PubMed  CAS  Google Scholar 

  52. Boyer LA, Lee TI, Cole MF, et al. Cell 2005;122:947–956.

    Article  PubMed  CAS  Google Scholar 

  53. Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Genes Dev 2003;17:126–140.

    Article  PubMed  CAS  Google Scholar 

  54. Reva T, Clevers H. Nature 2005;434:843–850.

    Article  CAS  Google Scholar 

  55. Gil J, Bernard D, Peters G. DNA Cell Biol 2005;24:117–125.

    Article  PubMed  CAS  Google Scholar 

  56. Cayuso J, Marti E. J Neurobiol 2005;64:376–387.

    Article  PubMed  Google Scholar 

  57. Molotsky AV, Pardal R, Morrison SI. Curr Opin Cell Biol 2004;16:700–707.

    Article  CAS  Google Scholar 

  58. Kleber M, Sommer L. Curr Opin Cell Biol 2004;16:681–687.

    Article  PubMed  CAS  Google Scholar 

  59. Kamachi Y, Uchikawa M, Kondoh H. Trends Genet 2000;16:182–187.

    Article  PubMed  CAS  Google Scholar 

  60. Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Iing N, Kondoh H. Mol Cell Biol 2004;24:8834–8846.

    Article  PubMed  CAS  Google Scholar 

  61. Kondoh H, Castro DS, and Guillemot F. Nat Rev Neurosci 2002; 3:517–530.

    Article  CAS  Google Scholar 

  62. Lee KJ, Jessell TM. Annu Rev Neurosci 1999;22:261–294.

    Article  PubMed  CAS  Google Scholar 

  63. Shirasaki R, Pfaff SL. Ann Rev Neurosci 2002;25:251–281.

    Article  PubMed  CAS  Google Scholar 

  64. Lee SK, Lee B, Ruiz EC, Pfaff SL. Genes Dev 2005;19:282–294.

    Article  PubMed  CAS  Google Scholar 

  65. Guidato S, Prin F, Guthrie S. Development 2003;130:2981–2996.

    Article  PubMed  CAS  Google Scholar 

  66. Sun T, Pringle NP, Hardy AP, Richardson WD, Smith HK. Mol Cell Neurosci 1998;12:228–239.

    Article  PubMed  CAS  Google Scholar 

  67. Takeuchi K, Mileikovskaia M, Koshiba-Takeuchi K, et al. Development 2005;132:2463–2474.

    Article  PubMed  CAS  Google Scholar 

  68. Thaler JP, Koo SJ, Kania A, et al. Neuron 2004:41:337–350.

    Article  PubMed  CAS  Google Scholar 

  69. Lu QR, Sun T, Zhu Z, et al. Cell 2002;10:75–86.

    Article  Google Scholar 

  70. Novitch BG, Chen AI, Jessell TM. Neuron 2001;31:773–789.

    Article  PubMed  CAS  Google Scholar 

  71. Zhou Q, Anderson DJ. Cell 2002;109:61–73.

    Article  PubMed  CAS  Google Scholar 

  72. Mizuguchi R, Sugimori M, Takebayashi H, et al. Neuron 2001;31: 757–771.

    Article  PubMed  CAS  Google Scholar 

  73. Briscoe J, Pierani A, Jessell TM, Ericson J. Cell 2000;101:435–445.

    Article  PubMed  CAS  Google Scholar 

  74. Thaler JP, Lee SK, Jurata LW, Gill GN, Pfaff SL. Cell 2002;110:237–249.

    Article  PubMed  CAS  Google Scholar 

  75. Zhou Q, Choi G, Anderson DJ. Neuron 2001;31:791–807.

    Article  PubMed  CAS  Google Scholar 

  76. Zhang X, Cai J, Klueber KM, et al. Stem Cells 2005;23:442–453.

    Article  PubMed  CAS  Google Scholar 

  77. Arnett HA, Fancy SP, Alberta JA, et al. Science 2004;306:2111–2115.

    Article  PubMed  CAS  Google Scholar 

  78. Balasubramanivan V, Timmer N, Kust B, Boddeke E, Copray S. Stem Cells 2004;22:878–882.

    Article  Google Scholar 

  79. Buzzard IJ, Gough NM, Crook JM, Colman A. Nat Biotechnol 2004;22:381–382, author reply 382.

    Article  PubMed  CAS  Google Scholar 

  80. Draper IS, Smith K, Gokhale P, et al. Nat Biotechnol 2004;22: 53, 54.

    Article  PubMed  CAS  Google Scholar 

  81. Maitra A, Arking DE, Shivapurkar N, et al. Nat Genet 2005; 37:1099–1103.

    Article  PubMed  CAS  Google Scholar 

  82. Mitalipova MM, Rao RR, Hoyer DM, et al. Nat Biotechnol 2005; 23:19, 20.

    Article  PubMed  CAS  Google Scholar 

  83. Ludwig TE, Levenstein ME, Jones JM, et al. Nat Biotechnol 2006;24:185–187.

    Article  PubMed  CAS  Google Scholar 

  84. Amit M, Carpenter MK, Inokuma MS, et al. Dev Biol 2000;227: 271–278.

    Article  PubMed  CAS  Google Scholar 

  85. Kaneko Y, Sakakibara S, Imai T, et al. Dev Neurosci 2000;22; 139–153.

    Article  PubMed  CAS  Google Scholar 

  86. Lendahl U, Zimmerman LB, McKay RD. Cell 1990;60:585–595.

    Article  PubMed  CAS  Google Scholar 

  87. Okano H, Kawahara H, Toriya M, Nakao K, Shibata S, Imai T. Exp Cell Res 2005;306:349–356.

    Article  PubMed  CAS  Google Scholar 

  88. Knoblich JA. Nat Rev Mol Cell Biol 2001;2:11–20.

    Article  PubMed  CAS  Google Scholar 

  89. Prokopenko SN, Chia W. Semin Cell Dev Biol 2005;16:423–437.

    Article  PubMed  CAS  Google Scholar 

  90. Zhang SC, Wernig M, Duncan ID, Brustle O, Thomson JA. Nat Biotechnol 2001;19:1129–1133.

    Article  PubMed  CAS  Google Scholar 

  91. Zhang SC, Ge B, Duncan ID. Proc Natl Acad Sci USA 1999;96: 4089–4094.

    Article  PubMed  CAS  Google Scholar 

  92. Zhang SC, Ge B, Duncan ID. J Neurosci Res 2000;59;421–429.

    Article  PubMed  CAS  Google Scholar 

  93. Pera MF, Andrade J, Houssami S, et al. J Cell Sci 2004;117: 1269–1280.

    Article  PubMed  CAS  Google Scholar 

  94. Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH. Nat Med 2004;10:55–63.

    Article  PubMed  CAS  Google Scholar 

  95. Xu RH, Peck RM, Li DS, Feng X, Ludwig T, Thomson JA. Nat Methods 2005;2:185–190.

    Article  PubMed  CAS  Google Scholar 

  96. Gerrard L, Rodgers L, Cui W. Stem Cells 2005;23:1234–1241.

    Article  PubMed  CAS  Google Scholar 

  97. Itsykson P, Ilouz N, Turetsky T, et al. Mol Cell Neurosci 2005;30:24–36.

    Article  PubMed  CAS  Google Scholar 

  98. Xu RH, Chen X, Li DS, et al. Nat Biotechnol 2002;20:1261–1264.

    Article  PubMed  CAS  Google Scholar 

  99. Ying QL, Nichols J, Chambers I, Smith A. Cell 2003a;115:281–292.

    Article  PubMed  CAS  Google Scholar 

  100. Shin S, Mitalipova M, Noggle S, et al. Stem Cells 2006;24:125–138.

    Article  PubMed  Google Scholar 

  101. Ying QL, Stavridis M, Griffiths D, Li M, Smith A. Nat Biotechnol 2003b;21:183–186.

    Article  PubMed  CAS  Google Scholar 

  102. Li XJ, Du ZW, Zarnowska ED, et al. Nat Biotechnol 2005;23:215–221.

    Article  PubMed  CAS  Google Scholar 

  103. Shin S, Dalton S, Stice SL. Stem Cells Dev 2005;14:266–269.

    Article  PubMed  CAS  Google Scholar 

  104. Copp AJ, Greene ND, Murdoch JN. Nat Rev Genet 2003;4: 784–793.

    Article  PubMed  Google Scholar 

  105. Wu P, Tarasenko YI, Gu Y, Huang LY, Coggeshall RE, Yu Y. Nat Neurosci 2002;5:1271–1278.

    Article  PubMed  CAS  Google Scholar 

  106. Singh Roy N, Nakano T, Xuing L, Kang J, Nedergaard M, Goldman SA. Exp Neurol 2005;196:224–234.

    Article  PubMed  CAS  Google Scholar 

  107. Wichterle H, Lieberam I, Porter IA, Jessell TM. Cell 2002;110: 385–397.

    Article  PubMed  CAS  Google Scholar 

  108. Arber S, Han B, Mendelsohn M, Smith M, Jessell TM, Sockanathan S. Neuron 1999;23:659–674.

    Article  PubMed  CAS  Google Scholar 

  109. Roy NS, Nakano T, Keyoung HM, et al. Nat Biotechnol 2004; 22:297–305.

    Article  PubMed  CAS  Google Scholar 

  110. Pfaff SL, Mendelsohn M, Stewart CL, Edlund T, Jessell TM. Cell 1996;84:309–320.

    Article  PubMed  CAS  Google Scholar 

  111. Kalb R. Trends Neurosci 2005;28:5–11.

    Article  PubMed  CAS  Google Scholar 

  112. Rao M, Sockanathan S. Science 2005;309:2212–2215.

    Article  PubMed  CAS  Google Scholar 

  113. Nistor GI, Totoiu MO, Haque N, Carpenter MK, Keirstead HS. Glia 2005;49:385–396.

    Article  PubMed  Google Scholar 

  114. Du ZW, Zhang SC. Stem Cells Dev 2004;13:372–381.

    Article  PubMed  Google Scholar 

  115. Kilpatrick TJ, Bartlett PF. Neuron 1993;10:255–265.

    Article  PubMed  CAS  Google Scholar 

  116. Rao M. Dev Biol 2004;275:269–286.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Regenerative Bioscience Center, University of Georgia, 125 River Rd, 30602, Athens, GA

    Patricia G. Wilson & Steve S. Stice

Authors
  1. Patricia G. Wilson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Steve S. Stice
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patricia G. Wilson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilson, P.G., Stice, S.S. Development and differentiation of neural rosettes derived from human embryonic stem cells. Stem Cell Rev 2, 67–77 (2006). https://doi.org/10.1007/s12015-006-0011-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-006-0011-1

Index Entries

Search

Navigation