Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Regionally specific induction by the Spemann–Mangold organizer

Nature Reviews Genetics volume 5, pages 425–434 (2004)Cite this article

Key Points

  • The Spemann–Mangold organizer is an axis-inducing centre that is evolutionarily conserved in vertebrates. It coordinates pattern formation along the anterior–posterior, dorsal–ventral and left–right axes.

  • Head, trunk and tail organizers can be distinguished on the basis of transplantation experiments in all vertebrates. They have different cell compositions and express distinct genes.

  • A long-standing question is whether the regionally specific inductions of the Spemann–Mangold organizer are the result of quantitative or qualitative mechanisms. Recent evidence indicates that both models apply.

  • The head organizer requires inhibition of BMP, Nodal and Wnt growth factors and expresses a corresponding set of growth-factor antagonists.

  • The trunk organizer requires inhibition of BMP growth factors and expresses a corresponding set of BMP antagonists. It requires Nodal and Wnt signals.

  • The tail organizer requires activity of BMP, Nodal and Wnt growth factors. In zebrafish, the tail organizer is composed of cells from the dorsal as well as the ventral side of the gastrula-stage embryo.

  • During embryonic axis formation, BMP, Nodal and Wnt growth factors act in signalling gradients to pattern embryonic cells in a dose-dependent fashion. Nodal is upstream of the orthogonal activity gradients of Wnt and BMP, which specify the anterior–posterior and dorsal–ventral axes; the three growth-factor pathways cross-regulate each other.

Abstract

Eighty years ago, Spemann and Mangold discovered the extraordinary inductive potency of the dorsal blastopore lip in amphibian embryos. Many inducers released by this organizer have now been identified and they typically encode antagonists of bone morphogenetic protein, Nodal or Wnt growth factors. The different expression domains of these growth factors and their antagonists create signalling gradients, which pattern the early embryo in a combinatorial fashion and explain the regional specificities of head, trunk and tail organizers. New findings indicate that both quantitative and qualitative mechanisms account for regionally specific organizer function.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Comparative diagram of Spemann–Mangold organizer development in (a) Xenopus laevis, (b) zebrafish, (c) chick and (d) mouse gastrulae.
Figure 2: Combinatorial action of Wnts, bone morphogenetic proteins and Nodals during axis formation.
Figure 3: Genetics of the role of Wnt/β-catenin signalling in the head organizer.
Figure 4: Formation of Nodal gradients in Xenopus laevis.
Figure 5: Cross-regulation of growth-factor signalling at the early gastrula stage.
Figure 6: Double-gradient model of embryonic axis formation.

Similar content being viewed by others

References

  1. De Robertis, E. M., Larrain, J., Oelgeschlager, M. & Wessely, O. The establishment of Spemann's organizer and patterning of the vertebrate embryo. Nature Rev. Genet. 1, 171–181 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Gilbert, S. F. & Saxen, L. Spemann's organizer: models and molecules. Mech. Dev. 41, 73–89 (1993).

    Article  CAS  PubMed  Google Scholar 

  3. Grunz, H. The vertebrate organizer (Springer, Berlin, Heidelberg, 2003).

    Google Scholar 

  4. Keller, R. Shaping the vertebrate body plan by polarized embryonic cell movements. Science 298, 1950–1954 (2003).

    Article  CAS  Google Scholar 

  5. Wilson, S. I. & Edlund, T. Neural induction: toward a unifying mechanism. Nature Neurosci. 4 (Suppl.), 1161–1168 (2001).

    Article  CAS  PubMed  Google Scholar 

  6. Stern, C. D. Initial patterning of the central nervous system: how many organizers? Nature Rev. Neurosci. 2, 92–98 (2001).

    Article  CAS  Google Scholar 

  7. Böttcher, R. T. & Niehrs, C. Fibroblast growth factor signalling during early vertebrate development. Endocrine Rev. (in the press).

  8. Maden, M. Retinoid signalling in the development of the central nervous system. Nature Rev. Neurosci. 3, 843–853 (2002).

    Article  CAS  Google Scholar 

  9. Pera, E. M. & Kessel, M. Patterning of the chick forebrain anlage by the prechordal plate. Development 124, 4153–4162 (1997).

    Article  CAS  PubMed  Google Scholar 

  10. Sagerstrom, C. G., Grinbalt, Y. & Sive, H. Anteroposterior patterning in the zebrafish, Danio rerio: an explant assay reveals inductive and suppressive cell interactions. Development 122, 1873–1883 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Saude, L., Woolley, K., Martin, P., Driever, W. & Stemple, D. L. Axis-inducing activities and cell fates of the zebrafish organizer. Development 127, 3407–3417 (2000).

    Article  CAS  PubMed  Google Scholar 

  12. Ang, S. L. & Rossant, J. Anterior mesendoderm induces mouse Engrailed genes in explant cultures. Development 118, 139–149 (1993). Shows that presumptive prechordal mesendoderm contains anterior neural-inducing activity.

    Article  CAS  PubMed  Google Scholar 

  13. Beddington, R. S. & Robertson, E. J. Anterior patterning in mouse. Trends Genet. 14, 277–284 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Knoetgen, H., Viebahn, C. & Kessel, M. Head induction in the chick by primitive endoderm of mammalian, but not avian origin. Development 126, 815–825 (1999).

    Article  CAS  PubMed  Google Scholar 

  15. Kimura, C. et al. Visceral endoderm mediates forebrain development by suppressing posteriorizing signals. Dev. Biol. 225, 304–321 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Kinder, S. J. et al. The organizer of the mouse gastrula is composed of a dynamic population of progenitor cells for the axial mesoderm. Development 128, 3623–3634 (2001). Refutes the view that head-organizer activity in the mouse resides exclusively in the anterior visceral endoderm; shows that definitive anterior mesendoderm that is derived from the primitive streak harbours head-organizer activity.

    Article  CAS  PubMed  Google Scholar 

  17. Tucker, A. S. & Slack, J. M. Tail bud determination in the vertebrate embryo. Curr. Biol. 5, 807–813 (1995).

    Article  CAS  PubMed  Google Scholar 

  18. Agathon, A., Thisse, C. & Thisse, B. The molecular nature of the zebrafish tail organizer. Nature 424, 448–452 (2003). Discovery of tail-inducer activity outside the Spemann–Mangold organizer and identification of the involvement of Wnt, bone morphogenetic proteins and Nodal signals.

    Article  CAS  PubMed  Google Scholar 

  19. Joubin, K. & Stern, C. Molecular interactions continously define the organizer during the cell movements of gastrulation. Cell 98, 559–571 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Kiecker, C. & Niehrs, C. The role of prechordal mesendoderm in neural patterning. Curr. Opin. Neurobiol. 11, 27–33 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Beddington, R. S. & Robertson, E. J. Axis development and early asymmetry in mammals. Cell 96, 195–209 (1999).

    Article  CAS  PubMed  Google Scholar 

  22. Schneider, V. A. & Mercola, M. Spatially distinct head and heart inducers within the Xenopus organizer region. Curr. Biol. 9, 800–809 (1999). Shows that head-organizer activity is predominatly located in presumptive prechordal mesendoderm, rather than the anterior endoderm.

    Article  CAS  PubMed  Google Scholar 

  23. Foley, A. C., Skromne, I. & Stern, C. D. Reconciling different models of forebrain induction and patterning: a dual role for the hypoblast. Development 127, 3839–3854 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Tam, P. P. & Steiner, K. A. Anterior patterning by synergistic activity of the early gastrula organizer and the anterior germ layer tissues of the mouse embryo. Development 126, 5171–5179 (1999).

    Article  CAS  PubMed  Google Scholar 

  25. Bradley, L., Wainstock, D. & Sive, H. Positive and negative signals modulate formation of the Xenopus cement gland. Development 122, 2739–2750 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Perea-Gomez, A. et al. Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks. Dev. Cell 3, 745–756 (2002). Shows that the role of Nodal antagonists is to negatively regulate mesoderm formation.

    Article  CAS  PubMed  Google Scholar 

  27. Chapman, S. C., Schubert, F. R., Schoenwolf, G. C. & Lumsden, A. Anterior identity is established in chick epiblast by hypoblast and anterior definitive endoderm. Development 130, 5091–5101 (2003).

    Article  CAS  PubMed  Google Scholar 

  28. Piccolo, S. et al. The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wnt signals. Nature 397, 707–710 (1999). Provides evidence that head induction is the result of triple inhibition of Nodal, bone morphogenetic proteins and Wnt signals.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Silva, A. C., Filipe, M., Kuerner, K. M., Steinbeisser, H. & Belo, J. A. Endogenous Cerberus activity is required for anterior head specification in Xenopus. Development 130, 4943–4953 (2003).

    Article  CAS  PubMed  Google Scholar 

  30. Pera, E. M., Wessely, O., Li, S. Y. & De Robertis, E. M. Neural and head induction by insulin-like growth factor signals. Dev. Cell 1, 655–665 (2001). Identifies the first instructive signal required for organizer function.

    Article  CAS  PubMed  Google Scholar 

  31. Bachiller, D. et al. The organizer factors Chordin and Noggin are required for mouse forebrain development. Nature 403, 658–661 (2000). The first evidence in the mouse that bone morphogenetic protein antagonists are required for axial patterning, and specifically for head induction.

    Article  CAS  PubMed  Google Scholar 

  32. del Barco Barrantes, I., Davidson, G., Gröne, H. J., Westphal, H. & Niehrs, C. Dkk1 and noggin cooperate in mammalian head induction. Genes Dev. 17, 2239–2344 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Agathon, A., Thisse, B. & Thisse, C. Morpholino knock-down of antivin1 and antivin2 upregulates nodal signaling. Genesis 30, 178–182 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Schier, A. F. Nodal signaling in vertebrate development. Annu. Rev. Cell Dev. Biol. 19, 589–621 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Gonzalez, E. M. et al. Head and trunk in zebrafish arise via coinhibition of BMP signaling by bozozok and chordino. Genes Dev. 14, 3087–3092 (2000). Genetic evidence that bone morphogenetic protein antagonists function in the trunk organizer. bozozok/chordino double mutants only form tails.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vonica, A. & Gumbiner, B. M. Zygotic Wnt activity is required for Brachyury expression in the early Xenopus laevis embryo. Dev. Biol. 250, 112–127 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Hoppler, S., Brown, J. D. & Moon, R. T. Expression of a dominant–negative Wnt blocks induction of MyoD in Xenopus embryos. Genes Dev. 10, 2805–2817 (1996).

    Article  CAS  PubMed  Google Scholar 

  38. Glinka, A., Wu, W., Onichtchouk, D., Blumenstock, C. & Niehrs, C. Head induction by simultaneous repression of Bmp and Wnt signalling in Xenopus. Nature 389, 517–519 (1997). Proposes that head and trunk organizers arise from differential inhibition of Wnt and bone morphogenetic protein growth factors.

    Article  CAS  PubMed  Google Scholar 

  39. Yasuo, H. & Lemaire, P. Role of Goosecoid, Xnot and Wnt antagonists in the maintenance of the notochord genetic programme in Xenopus gastrulae. Development 128, 3783–3793 (2001).

    Article  CAS  PubMed  Google Scholar 

  40. Ariizumi, T., Sawamura, K., Uchiyama, H. & Asashima, M. Dose and time-dependent mesoderm induction and outgrowth formation by activin A in Xenopus laevis. Int. J. Dev. Biol. 35, 407–414 (1991).

    CAS  PubMed  Google Scholar 

  41. Ruiz i Altaba, A. & Melton, D. A. Interaction between peptide growth factors and homoeobox genes in the establishment of antero–posterior polarity in frog embryos. Nature 341, 33–38 (1989). One of the earliest papers to show region-specific axis inductions by different growth factors.

    Article  CAS  PubMed  Google Scholar 

  42. Alvarez, I. S., Araujo, M. & Nieto, M. A. Neural induction in whole chick embryo cultures by FGF. Dev. Biol. 199, 42–54 (1998).

    Article  CAS  PubMed  Google Scholar 

  43. Storey, K. G. et al. Early posterior neural tissue is induced by FGF in the chick embryo. Development 125, 473–484 (1998).

    Article  CAS  PubMed  Google Scholar 

  44. Gont, L. K., Steinbeisser, H., Blumberg, B. & De Robertis, E. M. Tail formation as a continuation of gastrulation: the multiple cell populations of the Xenopus tailbud derive from the late blastopore lip. Development 119, 991–1004 (1993).

    Article  CAS  PubMed  Google Scholar 

  45. Knezevic, V., De Santo, R. & Mackem, S. Continuing organizer function during chick tail development. Development 125, 1791–1801 (1998).

    Article  CAS  PubMed  Google Scholar 

  46. Beck, C. W. & Slack, J. M. A developmental pathway controlling outgrowth of the Xenopus tail bud. Development 126, 1611–1620 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Beck, C. W., Whitman, M. & Slack, J. M. The role of BMP signaling in outgrowth and patterning of the Xenopus tail bud. Dev. Biol. 238, 303–314 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Gawantka, V. et al. Gene expression screening in Xenopus identifies molecular pathways, predicts gene function and provides a global view of embryonic patterning. Mech. Dev. 77, 95–141 (1998).

    Article  CAS  PubMed  Google Scholar 

  49. Whitman, M. Nodal signaling in early vertebrate embryos: themes and variations. Dev. Cell 1, 605–617 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Green, J. B. & Smith, J. C. Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate. Nature 347, 391–394 (1990). The first evidence for a TGF-β functioning in a graded fashion in embryonic patterning.

    Article  CAS  PubMed  Google Scholar 

  51. Gurdon, J. B., Harger, P., Mitchell, A. & Lemaire, P. Activin signalling and response to a morphogen gradient. Nature 371, 487–492 (1994). Original study that showed long-range patterning effects of a TGF-β.

    Article  CAS  PubMed  Google Scholar 

  52. Agius, E., Oelgeschlager, M., Wessely, O., Kemp, C. & De Robertis, E. M. Endodermal Nodal-related signals and mesoderm induction in Xenopus. Development 127, 1173–1183 (2000).

    Article  CAS  PubMed  Google Scholar 

  53. Lee, M. A., Heasman, J. & Whitman, M. Timing of endogenous activin-like signals and regional specification of the Xenopus embryo. Development 128, 2939–2952 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Kofron, M. et al. Mesoderm induction in Xenopus is a zygotic event regulated by maternal VegT via TGFβ growth factors. Development 126, 5759–5770 (1999).

    Article  CAS  PubMed  Google Scholar 

  55. Schohl, A. & Fagotto, F. β-catenin, MAPK and Smad signaling during early Xenopus development. Development 129, 37–52 (2002).

    Article  CAS  PubMed  Google Scholar 

  56. Faure, S., Lee, M. A., Keller, T., ten Dijke, P. & Whitman, M. Endogenous patterns of TGFβ superfamily signaling during early Xenopus development. Development 127, 2917–2931 (2000).

    Article  CAS  PubMed  Google Scholar 

  57. Thisse, B., Wright, C. V. & Thisse, C. Activin- and Nodal-related factors control antero–posterior patterning of the zebrafish embryo. Nature 403, 425–428 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Gritsman, K., Talbot, W. S. & Schier, A. F. Nodal signaling patterns the organizer. Development 127, 921–932 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. Dougan, S. T., Warga, R. M., Kane, D. A., Schier, A. F. & Talbot, W. S. The role of the zebrafish nodal-related genes squint and cyclops in patterning of mesendoderm. Development 130, 1837–1851 (2003).

    Article  CAS  PubMed  Google Scholar 

  60. Lowe, L. A., Yamada, S. & Kuehn, M. R. Genetic dissection of nodal function in patterning the mouse embryo. Development 128, 1831–1843 (2001).

    Article  CAS  PubMed  Google Scholar 

  61. Vincent, S. D., Dunn, N. R., Hayashi, S., Norris, D. P. & Robertson, E. J. Cell fate decisions within the mouse organizer are governed by graded Nodal signals. Genes Dev. 17, 1646–1662 (2003). Together with reference 82, this presents a rare case of a study on dose-dependent patterning effects by a growth factor in the mouse.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lane, M. C. & Smith, W. C. The origins of primitive blood in Xenopus: implications for axial patterning. Development 126, 423–434 (1999).

    Article  CAS  PubMed  Google Scholar 

  63. Wessely, O., Agius, E., Oelgeschlager, M., Pera, E. M. & De Robertis, E. M. Neural induction in the absence of mesoderm: β-catenin-dependent expression of secreted BMP antagonists at the blastula stage in Xenopus. Dev. Biol. 234, 161–173 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Feldman, B. et al. Zebrafish organizer development and germ-layer formation require nodal-related signals. Nature 395, 181–185 (1998).

    Article  CAS  PubMed  Google Scholar 

  65. Dosch, R., Gawantka, V., Delius, H., Blumenstock, C. & Niehrs, C. Bmp-4 acts as a morphogen in dorsoventral mesoderm patterning in Xenopus. Development 124, 2325–2334 (1997).

    Article  CAS  PubMed  Google Scholar 

  66. Wilson, P. A., Lagna, G., Suzuki, A. & Hemmati-Brivanlou, A. Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1. Development 124, 3177–3184 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Knecht, A. & Harland, R. M. Mechanisms of dorsal–ventral paterning in noggin-induced neural tissue. Development 124, 2477–2488 (1997).

    Article  CAS  PubMed  Google Scholar 

  68. Kishimoto, Y., Lee, K. H., Zon, L., Hammerschmidt, M. & Schulte, M. S. The molecular nature of zebrafish swirl: BMP2 function is essential during early dorsoventral patterning. Development 124, 4457–4466 (1997).

    Article  CAS  PubMed  Google Scholar 

  69. Nguyen, V. H. et al. Ventral and lateral regions of the zebrafish gastrula, including the neural crest progenitors, are established by a bmp2b/swirl pathway of genes. Dev. Biol. 199, 93–110 (1998).

    Article  CAS  PubMed  Google Scholar 

  70. Dick, A. et al. Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo. Development 127, 343–354 (2000).

    Article  CAS  PubMed  Google Scholar 

  71. Schmid, B. et al. Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. Development 127, 957–967 (2000).

    Article  CAS  PubMed  Google Scholar 

  72. Hild, M. et al. The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral patterning of the zebrafish embryo. Development 126, 2149–2159 (1999).

    Article  CAS  PubMed  Google Scholar 

  73. Schulte-Merker, S., Lee, K. J., McMahon, A. P. & Hammerschmid, M. The zebrafish organizer requires chordino. Nature 387, 862–863 (1997).

    Article  CAS  PubMed  Google Scholar 

  74. Barth, K. A. et al. Bmp activity establishes a gradient of positional information throughout the entire neural plate. Development 126, 4977–4987 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Neave, B., Holder, N. & Patient, R. A graded response to BMP-4 spatially coordinates patterning ofthe mesoderm and ectoderm in the zebrafish. Mech. Dev. 62, 103–246 (1997).

    Article  Google Scholar 

  76. Winnier, G., Blessing, M., Labosky, P. A. & Hogan, B. L. Bone morphogenetic protein 4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 9, 2105–2116 (1995).

    Article  CAS  PubMed  Google Scholar 

  77. McGrew, L. L., Lai, C. J. & Moon, R. T. Specification of the anteroposterior neural axis through synergistic interaction of the Wnt signaling cascade with noggin and follistatin. Dev. Biol. 172, 337–342 (1995). An early paper that showed that Wnts can posteriorize central nervous system development.

    Article  CAS  PubMed  Google Scholar 

  78. Kiecker, C. & Niehrs, C. A morphogen gradient of Wnt/β-catenin signalling regulates anteroposterior neural patterning in Xenopus. Development 128, 4189–4201 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Nordstrom, U., Jessell, T. M. & Edlund, T. Progressive induction of caudal neural character by graded Wnt signaling. Nature Neurosci. 5, 525–532 (2002).

    Article  PubMed  Google Scholar 

  80. Lekven, A. C., Thorpe, C. J., Waxman, J. S. & Moon, R. T. Zebrafish wnt8 encodes two wnt8 proteins on a bicistronic transcript and is required for mesoderm and neurectoderm patterning. Dev. Cell 1, 103–114 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Erter, C. E., Wilm, T. P., Basler, N., Wright, C. V. & Solnica-Krezel, L. Wnt8 is required in lateral mesendodermal precursors for neural posteriorization in vivo. Development 128, 3571–3583 (2001).

    Article  CAS  PubMed  Google Scholar 

  82. Greco, T. L. et al. Analysis of the vestigial tail mutation demonstrates that Wnt-3a gene dosage regulates mouse axial development. Genes Dev. 10, 313–324 (1996).

    Article  CAS  PubMed  Google Scholar 

  83. Marvin, M. J., Di Rocco, G., Gardiner, A., Bush, S. M. & Lassar, A. B. Inhibition of Wnt activity induces heart formation from posterior mesoderm. Genes Dev. 15, 316–327 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kazanskaya, O., Glinka, A. & Niehrs, C. The role of Xenopus dickkopf1 in prechordal plate specification and neural patterning. Development 127, 4981–4992 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Aybar, M. J. & Mayor, R. Early induction of neural crest cells: lessons learned from frog, fish and chick. Curr. Opin. Genet. Dev. 12, 452–458 (2002).

    Article  CAS  PubMed  Google Scholar 

  86. Strigini, M. & Cohen, S. M. Formation of morphogen gradients in the Drosophila wing. Semin. Cell Dev. Biol. 10, 335–344 (1999).

    Article  CAS  PubMed  Google Scholar 

  87. Hoppler, S. & Moon, R. T. BMP-2/-4 and Wnt-8 cooperatively pattern the Xenopus mesoderm. Mech. Dev. 71, 119–129 (1998).

    Article  CAS  PubMed  Google Scholar 

  88. Graff, J. M., Thies, R. S., Song, J. J., Celeste, A. J. & Melton, D. A. Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo. Cell 79, 169–179 (1994). Together with reference 104, this paper showed for the first time that the organizer is antagonized by bone morphogenetic proteins, and provided the basis for understanding its molecular nature.

    Article  CAS  PubMed  Google Scholar 

  89. de Souza, F. S. et al. The zinc finger gene Xblimp1 controls anterior endomesodermal cell fate in Spemann's organizer. EMBO J. 18, 6062–6072 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Dosch, R. & Niehrs, C. Requirement for anti-dorsalizing morphogenetic protein in organizer patterning. Mech. Dev. 90, 195–203 (2000).

    Article  CAS  PubMed  Google Scholar 

  91. Gerhart, J. Evolution of the organizer and the chordate body plan. Int. J. Dev. Biol. 45, 133–153 (2001).

    CAS  PubMed  Google Scholar 

  92. Glinka, A. et al. Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391, 357–362 (1998).

    Article  CAS  PubMed  Google Scholar 

  93. Houart, C. et al. Establishment of the telencephalon during gastrulation by local antagonism of Wnt signaling. Neuron 35, 255–265 (2002).

    Article  CAS  PubMed  Google Scholar 

  94. Kim, C. H. et al. Repressor activity of Headless/Tcf3 is essential for vertebrate head formation. Nature 407, 913–916 (2000). First genetic evidence that head-organizer activity requires Wnt inhibition.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Heisenberg, C. P. et al. A mutation in the Gsk3-binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon. Genes Dev. 15, 1427–1434 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. van de Water, S. et al. Ectopic Wnt signal determines the eyeless phenotype of zebrafish masterblind mutant. Development 128, 3877–3888 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Kim, S. H. et al. Specification of an anterior neuroectoderm patterning by Frizzled8a-mediated Wnt8b signalling during late gastrulation in zebrafish. Development 129, 4443–4455 (2002).

    Article  CAS  PubMed  Google Scholar 

  98. Connors, S. A., Trout, J., Ekker, M. & Mullins, M. C. Role of tolloid/mini fin in dorsoventral pattern formation of the zebrafish embryo. Development 126, 3119–3130 (1999).

    Article  CAS  PubMed  Google Scholar 

  99. Mullins, M. C. et al. Genes establishing dorsoventral pattern formation in the zebrafish embryo: the ventral specifying genes. Development 123, 81–93 (1996).

    Article  CAS  PubMed  Google Scholar 

  100. Gritsman, K. et al. The EGF-CFC protein one-eyed pinhead is essential for Nodal signaling. Cell 97, 121–132 (1999).

    Article  CAS  PubMed  Google Scholar 

  101. Davidson, G., Mao, B., Del Barco Barrantes, I. & Niehrs, C. Kremen proteins interact with Dickkopf1 to regulate anteroposterior CNS patterning. Development 129, 5587–5596 (2002).

    Article  CAS  PubMed  Google Scholar 

  102. Oelgeschläger, M., Kuroda, H., Reversade, B. & Robertis, E. M. Chordin is required for the Spemann organizer transplantation phenomenon in Xenopus embryos. Dev. Cell 4, 219–230 (2003).

    Article  PubMed  Google Scholar 

  103. Sedohara, A., Fukui, A., Michiue, T. & Asashima, M. Role of BMP-4 in the inducing ability of the head organizer in Xenopus laevis. Zoolog. Sci. 19, 67–80 (2002).

    Article  CAS  PubMed  Google Scholar 

  104. Suzuki, A. et al. A truncated bone morphogenetic protein receptor affects dorsal–ventral patterning in the early Xenopus embryo. Proc. Natl Acad. Sci. USA 91, 10255–10259 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Smith, W. C. & Harland, R. M. Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Cell 70, 829–840 (1992). The first growth-factor antagonist discovered as an effector of the Spemann organizer.

    Article  CAS  PubMed  Google Scholar 

  106. Sasai, Y. et al. Xenopus chordin: a novel dorsalizing factor activated by organizer-specific homeobox genes. Cell 79, 779–790 (1994). Discovery of Chordin, an evolutionarily conserved bone morphogenetic protein antagonist of the Spemann organizer.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Smith, J. C., Price, B. M., Van, N. K. & Huylebroeck, D. Identification of a potent Xenopus mesoderm-inducing factor as a homologue of activin A. Nature 345, 729–731 (1990).

    Article  CAS  PubMed  Google Scholar 

  108. Streit, A. et al. Chordin regulates primitive streak development and the stability of induced neural cells, but is not sufficient for neural induction in the chick embryo. Development 125, 507–519 (1998).

    Article  CAS  PubMed  Google Scholar 

  109. Mitrani, E. et al. Activin can induce the formation of axial structures and is expressed in the hypoblast of the chick. Cell 63, 495–501 (1990).

    Article  CAS  PubMed  Google Scholar 

  110. Bertocchini, F. & Stern, C. D. The hypoblast of the chick embryo positions the primitive streak by antagonizing Nodal signaling. Dev. Cell 3, 735–744 (2002).

    Article  CAS  PubMed  Google Scholar 

  111. Mukhopadhyay, M. et al. Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev. Cell 1, 423–434 (2001).

    Article  CAS  PubMed  Google Scholar 

  112. Lagutin, O. V. et al. Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development. Genes Dev. 17, 368–379 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Liu, P. et al. Requirement for Wnt3 in vertebrate axis formation. Nature Genet. 22, 361–365 (1999).

    Article  CAS  PubMed  Google Scholar 

  114. Yamaguchi, T. P., Bradley, A., McMahon, A. P. & Jones, S. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126, 1211–1223 (1999).

    Article  CAS  PubMed  Google Scholar 

  115. Pinson, K. I., Brennan, J., Monkley, S., Avery, B. J. & Skarnes, W. C. An LDL-receptor-related protein mediates Wnt signalling in mice. Nature 407, 535–538 (2000).

    Article  CAS  PubMed  Google Scholar 

  116. Galceran, J., Farinas, I., Depew, M. J., Clevers, H. & Grosschedl, R. Wnt3a−/−-like phenotype and limb deficiency in Lef1(−/−)Tcf1(−/−) mice. Genes Dev. 13, 709–717 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Kalantry, S. et al. The amnionless gene, essential for mouse gastrulation, encodes a visceral-endoderm-specific protein with an extracellular cysteine-rich domain. Nature Genet. 27, 412–416 (2001).

    Article  CAS  PubMed  Google Scholar 

  118. Conlon, F. L. et al. A primary requirement for nodal in the formation and maintenance of the primitive streak in the mouse. Development 120, 1919–1928 (1994).

    Article  CAS  PubMed  Google Scholar 

  119. Heasman, J., Kofron, M. & Wylie, C. β-catenin signaling activity dissected in the early Xenopus embryo: a novel antisense approach. Dev. Biol. 222, 124–134 (2000). The first paper to introduce morpholino antisense oligonucleotides into developmental biology. It also highlights the inhibitory role of β-catenin in head induction.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Christof Niehrs

Authors
  1. Christof Niehrs
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

DATABASES

Entrez

bmp2

bmp4

bmp7

bozozok

brachyury

chordin

Crescent

derriere

Dkk1

flh

follistatin

Frzb-1

gsc

Hex

noggin

Six3

Smad2

Smad3

smad5

tcf3

Wnt3a

Xnot

FURTHER INFORMATION

Axeldb

Dynamic development

The zebrafish information network

Xenbase

Glossary

DORSAL BLASTOPORE LIP

The region in amphibian embryos where gastrulation begins. Also known as the Spemann–Mangold organizer.

ORGANISIN

An elusive compound that was predicted by Dalq and Pasteels in the1930s to be emitted by the Spemann–Mangold organizer and its derivatives. Its regional distribution followed sulfhydryl-rich proteins.

WNTS

A growth-factor family that acts through seven transmembrane receptors.

GASTRULATION

A morphogenetic process that leads to the formation of the germ layers and the body plan.

BONE MORPHOGENETIC PROTEINS

(BMPs). A subfamily of the transforming growth factor β-superfamily.

NODALS

A subfamily of the transforming growth factor β-superfamily.

SECONDARY EMBRYONIC AXIS

A twin embryo that is induced by transplantation of the Spemann–Mangold organizer or by manipulation of organizer effectors.

NEURULA

The embryonic stage when the central nervous system forms the neural tube.

ANIMAL POLE

In amphibians and zebrafish, the top-most pole of the embryo.

ANTERIOR ENDODERM

An embryonic tissue that is derived from the Spemann–Mangold organizer/Hensen's node, which will form the foregut and pharynx.

EPIBLAST

The outer layer of the blastoderm in the chicken; the epiblast gives rise to the definitive embryonic tissues.

HYPOBLAST

The inner layer of the blastoderm in the chicken, which covers the yolk; the hypoblast gives rise to extraembryonic tissues.

PRIMITIVE STREAK

An elongated structure that is formed by an accumulation of cells, through which cells gastrulate.

ECTODERM, MESODERM AND ENDODERM

The three germ layers that give rise to all somatic tissues in animals.

GASTRULA

The embryonic stage when the germ layers aquire the final position relative to each other through a complex process of morphogenetic movements.

PRESUMPTIVE PRECHORDAL MESENDODERM

An embryonic tissue that is derived from the Spemann–Mangold organizer/Hensen's node, which will form the pharynx and head mesenchyme.

BLASTOCOEL

A fluid-filled cavity that develops in the interior of the blastula in amphibian embryos.

PRESUMPTIVE CHORDAMESODERM

An embryonic tissue that is derived from the Spemann–Mangold organizer/Hensen's node, which will form the notochord.

HENSEN'S NODE

A condensation of cells in the primitive streak in, for example, chick and mouse embryos, that contains organizer activity.

TAILBUD STAGE

The embryonic stage when neurulation is completed and tail formation begins, visible by an emerging tail primordium.

BLASTULA

An early-stage embryo that is composed of a hollow ball of cells.

MORPHOGEN

A substance that is active in pattern formation, the spatial concentration or activity of which varies, and to which cells respond differently at different threshold concentrations.

VEGETAL POLE

In amphibians and zebrafish, the bottom-most, yolk-rich pole of the embryo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Niehrs, C. Regionally specific induction by the Spemann–Mangold organizer. Nat Rev Genet 5, 425–434 (2004). https://doi.org/10.1038/nrg1347

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg1347

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing