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  • Review Article
  • Published:

The floor plate: multiple cells, multiple signals

Nature Reviews Neuroscience volume 6, pages 230–240 (2005)Cite this article

Key Points

  • The floor plate is a small group of cells located at the ventral midline of the neural tube that profoundly influences the development of the vertebrate nervous system by specifying cellular identities and directing axonal trajectories.

  • This review focuses on evidence that the floor plate is not composed of a uniform population of cells along the anteroposterior (AP) axis, and discusses the implications of this finding for resolving recent controversies about the embryological origin of the floor plate and the inductive mechanisms that control its development.

  • In the classic floor plate induction model, floor plate cells differentiate from neuroepithelial cells that occupy a ventral midline position, and are induced to a floor plate fate under the influence of signals from the underlying notochord. However, a second model proposes that some floor plate cells are induced early, during gastrulation, by prechordal mesoderm.

  • There are three main lines of evidence for AP differences in floor plate cells. First, there are molecular and morphological differences along the AP axis. Second, the floor plate seems to have separate embryological origins and ontogeny at different AP levels. Last, distinct inductive processes seem to be involved in the specification of the floor plate at different AP levels.

  • The initial evidence for AP differences in floor plate cells came from experiments in chick embryos, and promoter/enhancer studies in the mouse and zebrafish are beginning to indicate that floor plate-specific genes are regulated in distinct ways along the AP axis in these organisms.

  • Studies in amniotes indicate that sonic hedgehog is required for floor plate induction, whereas studies in zebrafish emphasize a requirement for the transforming growth factor-β family member Nodal. However, this distinction between zebrafish and amniotes might not be as clear-cut as was initially thought. One possibility is that Nodal has a pivotal role in the induction of the early-induced, predominantly anterior floor plate population, whereas hedgehog functions primarily to induce the later-arising posterior floor plate cells.

Abstract

One of the key organizers in the CNS is the floor plate — a group of cells that is responsible for instructing neural cells to acquire distinctive fates, and that has an important role in establishing the elaborate neuronal networks that underlie the function of the brain and spinal cord. In recent years, considerable controversy has arisen over the mechanism by which floor plate cells form. Here, we describe recent evidence that indicates that discrete populations of floor plate cells, with characteristic molecular properties, form in different regions of the neuraxis, and we discuss data that imply that the mode of floor plate induction varies along the anteroposterior axis.

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Figure 1: Heterogeneity in floor plate cells.
Figure 2: Origin and ontogeny of floor plate cells.
Figure 3: Transcriptional regulation of sonic hedgehog in the mouse.
Figure 4: Models for Nodal action in floor plate induction.

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References

  1. Jessell, T. M. & Dodd, J. Floor plate-derived signals and the control of neural cell pattern in vertebrates. Harvey Lect. 86, 87–128 (1990).

    PubMed  Google Scholar 

  2. Kingsbury, B. F. The developmental significance of the floor plate of the brain and spinal cord. J. Comp. Neurol. 50, 177–207 (1930). A review of the early floor plate literature, focusing, in part, on the AP extent of floor plate cells.

    Google Scholar 

  3. Kingsbury, B. F. The extent of the floor plate of His and its significance. J. Comp. Neurol. 32, 113–135 (1920).

    Google Scholar 

  4. His, W. Zur Geschichte des Gehirns, sowie der centralen und peripherischen Nervenbahnen beim menschlichen embryo. Abd. d. math. phys. Kl. d. Konigl. Sachsischen Gesellschaft d. Wiss 14, 341–392 (1888).

    Google Scholar 

  5. Ericson, J., Briscoe, J., Rashbass, P., van Heyningen, V. & Jessell, T. M. Graded sonic hedgehog signaling and the specification of cell fate in the ventral neural tube. Cold Spring Harb. Symp. Quant. Biol. 62, 451–466 (1997).

    CAS  PubMed  Google Scholar 

  6. Patten, I. & Placzek, M. The role of Sonic hedgehog in neural tube patterning. Cell. Mol. Life Sci. 57, 1695–1708 (2000).

    CAS  PubMed  Google Scholar 

  7. Lewis, K. E. & Eisen, J. S. From cells to circuits: development of the zebrafish spinal cord. Prog. Neurobiol. 69, 419–449 (2003).

    CAS  PubMed  Google Scholar 

  8. Marti, E., Bumcrot, D. A., Takada, R. & McMahon, A. P. Requirement of 19K form of Sonic hedgehog for induction of distinct ventral cell types in CNS explants. Nature 375, 322–325 (1995). Neural explants were exposed to recombinant SHH, and high concentrations of SHH were found to induce floor plate tissue. The inducing activity was shown to reside in a highly conserved 19K amino (N)-terminal peptide.

    CAS  PubMed  Google Scholar 

  9. Kessaris, N., Pringle, N. & Richardson, W. D. Ventral neurogenesis and the neuron-glial switch. Neuron 31, 677–680 (2001).

    CAS  PubMed  Google Scholar 

  10. Briscoe, J. & Ericson, J. The specification of neuronal identity by graded sonic hedgehog signalling. Sem. Cell Dev. Biol. 10, 353–362 (1999).

    CAS  Google Scholar 

  11. Colamarino, S. A. & Tessier-Lavigne, M. The role of the floor plate in axon guidance. Annu. Rev. Neurosci. 18, 497–529 (1995).

    CAS  PubMed  Google Scholar 

  12. Charron, F., Stein, E., Jeong, J., McMahon, A. P. & Tessier-Lavigne, M. The morphogen sonic hedgehog is an axonal chemoattractant that collaborates with netrin-1 in midline axon guidance. Cell 113, 11–23 (2003).

    CAS  PubMed  Google Scholar 

  13. Salinas, P. C. The morphogen sonic hedgehog collaborates with netrin-1 to guide axons in the spinal cord. Trends Neurosci. 26, 641–643 (2003).

    CAS  PubMed  Google Scholar 

  14. Liu, A., Majumdar, A., Schauerte, H. E., Haffter, P. & Drummond, I. A. Zebrafish wnt4b expression in the floor plate is altered in sonic hedgehog and gli-2 mutants. Mech. Dev. 91, 409–413 (2000).

    CAS  PubMed  Google Scholar 

  15. McGrew, L. L., Otte, A. P. & Moon, R. T. Analysis of Xwnt-4 in embryos of Xenopus laevis: a Wnt family member expressed in the brain and floor plate. Development 115, 463–473 (1992).

    CAS  PubMed  Google Scholar 

  16. Lyuksyutova, A. I. et al. Anterior–posterior guidance of commissural axons by Wnt–frizzled signaling. Science 302, 1984–1988 (2003).

    CAS  PubMed  Google Scholar 

  17. Dale, K. et al. Differential patterning of ventral midline cells by axial mesoderm is regulated by BMP7 and chordin. Development 126, 397–408 (1999).

    CAS  PubMed  Google Scholar 

  18. Furuta, Y., Piston, D. W. & Hogan, B. L. Bone morphogenetic proteins (BMPs) as regulators of dorsal forebrain development. Development 124, 2203–2212 (1997).

    CAS  PubMed  Google Scholar 

  19. Placzek, M. The role of the notochord and floor plate in inductive interactions. Curr. Opin. Genet. Dev. 5, 499–506 (1995).

    CAS  PubMed  Google Scholar 

  20. Sasaki, H. & Hogan, B. L. Enhancer analysis of the mouse HNF-3β gene: regulatory elements for node/notochord and floor plate are independent and consist of multiple sub-elements. Genes Cells 1, 59–72 (1996).

    CAS  PubMed  Google Scholar 

  21. Ruiz i Altaba, A., Jessell, T. M. & Roelink, H. Restrictions to floor plate induction by hedgehog and winged-helix genes in the neural tube of frog embryos. Mol. Cell. Neurosci. 6, 106–121 (1995).

    CAS  PubMed  Google Scholar 

  22. Jeong, Y. & Epstein, D. J. Distinct regulators of Shh transcription in the floor plate and notochord indicate separate origins for these tissues in the mouse node. Development 130, 3891–3902 (2003). The cis -acting sequences that regulate the SHH floor plate enhancer SFPE2 were characterized in this study. The highly conserved binding sites that match the consensus for homeodomain, FOXA and FOXH1 transcription factors were identified. Mutational analysis revealed that the HD and FOXA-binding sites are both required for activation of the SHH floor plate enhancer, but that the FOXH1-binding site is not required. In addition, mutational analysis revealed that a T-box-binding site normally mediates Shh suppression in p4/p5. This study also provides evidence that the floor plate and notochord arise from distinct precursors in the mouse node.

    CAS  PubMed  Google Scholar 

  23. Rastegar, S. et al. A floor plate enhancer of the zebrafish netrin1 gene requires Cyclops (Nodal) signalling and the winged helix transcription factor FoxA2. Dev. Biol. 252, 1–14 (2002). This study demonstrates a role for FoxA2 in zebrafish floor plate differentiation. Analysis of FoxA2 morphant embryos shows that expression of floor plate markers is substantially reduced in the posterior neuraxis, but is unaffected in the ventral forebrain.

    CAS  PubMed  Google Scholar 

  24. Epstein, D. J., McMahon, A. P. & Joyner, A. L. Regionalization of Sonic hedgehog transcription along the anteroposterior axis of the mouse central nervous system is regulated by Hnf3-dependent and -independent mechanisms. Development 126, 281–292 (1999). This study identified three enhancers that direct Shh expression to distinct regions along the AP axis. Analysis of regulatory sequences indicated that FOXA2-dependent and -independent mechanisms direct Shh expression in the floor plate.

    CAS  PubMed  Google Scholar 

  25. Strahle, U., Blader, P. & Ingham, P. W. Expression of axial and sonic hedgehog in wildtype and midline defective zebrafish embryos. Int. J. Dev. Biol. 40, 929–940 (1996).

    CAS  PubMed  Google Scholar 

  26. Charrier, J. B., Lapointe, F., Le Douarin, N. M. & Teillet, M. A. Dual origin of the floor plate in the avian embryo. Development 129, 4785–4796 (2002).

    CAS  PubMed  Google Scholar 

  27. Marti, E., Takada, R., Bumcrot, D. A., Sasaki, H. & McMahon, A. P. Distribution of Sonic hedgehog peptides in the developing chick and mouse embryo. Development 121, 2537–2547 (1995).

    CAS  PubMed  Google Scholar 

  28. Odenthal, J., van Eeden, F. J., Haffter, P., Ingham, P. W. & Nusslein-Volhard, C. Two distinct cell populations in the floor plate of the zebrafish are induced by different pathways. Dev. Biol. 219, 350–363 (2000).

    CAS  PubMed  Google Scholar 

  29. Strahle, U., Lam, C. S., Ertzer, R. & Rastegar, S. Vertebrate floor-plate specification: variations on common themes. Trends Genet. 20, 155–162 (2004).

    PubMed  Google Scholar 

  30. Jessell, T. M., Bovolenta, P., Placzek, M., Tessier-Lavigne, M. & Dodd, J. Polarity and patterning in the neural tube: the origin and function of the floor plate. Ciba Found. Symp. 144, 255–276 (1989).

    CAS  PubMed  Google Scholar 

  31. Wilson, S. W. & Houart, C. Early steps in the development of the forebrain. Dev. Cell 6, 167–181 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Rubenstein, J. L., Shimamura, K., Martinez, S. & Puelles, L. Regionalization of the prosencephalic neural plate. Annu. Rev. Neurosci. 21, 445–477 (1998).

    CAS  PubMed  Google Scholar 

  33. Krauss, S., Concordet, J. P. & Ingham, P. W. A functionally conserved homolog of the Drosophila segment polarity gene hh is expressed in tissues with polarizing activity in zebrafish embryos. Cell 75, 1431–1444 (1993). This paper reports the cloning of the zebrafish shh gene. Ectopic expression of Shh in normal embryos provides evidence for a role for Shh in floor plate induction.

    CAS  PubMed  Google Scholar 

  34. Roelink, H. et al. Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord. Cell 76, 761–775 (1994). Evidence that SHH can directly induce floor plate cells is described in this article. The N-terminal product of SHH, SHH-N, was shown to induce floor plate cells in explants of neural plate in vitro.

    CAS  PubMed  Google Scholar 

  35. Ruiz i Altaba, A., Placzek, M., Baldassare, M., Dodd, J. & Jessell, T. M. Early stages of notochord and floor plate development in the chick embryo defined by normal and induced expression of HNF-3β. Dev. Biol. 170, 299–313 (1995).

    PubMed  Google Scholar 

  36. Ruiz i Altaba, A., Prezioso, V. R., Darnell, J. E. & Jessell, T. M. Sequential expression of HNF-3β and HNF-3α by embryonic organizing centers: the dorsal lip/node, notochord and floor plate. Mech. Dev. 44, 91–108 (1993).

    CAS  PubMed  Google Scholar 

  37. Echelard, Y. et al. Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75, 1417–1430 (1993). This article reports the identification of mouse homologues of the Drosophila melanogaster hh gene, including Shh . It demonstrates that Shh is expressed in the notochord and floor plate and that ectopic expression activates floor plate genes.

    CAS  PubMed  Google Scholar 

  38. Riddle, R. D., Johnson, R. L., Laufer, E. & Tabin, C. Sonic hedgehog mediates the polarizing activity of the ZPA. Cell 75, 1401–1416 (1993).

    CAS  PubMed  Google Scholar 

  39. Schier, A. F., Neuhauss, S. C., Helde, K. A., Talbot, W. S. & Driever, W. The one-eyed pinhead gene functions in mesoderm and endoderm formation in zebrafish and interacts with no tail. Development 124, 327–342 (1997). Analysis of combinatorial zebrafish mutant embryos indicates a differential genetic requirement for the differentiation of floor plate cells along the AP axis. In addition, this study indicates a role for prechordal mesoderm in floor plate formation in zebrafish.

    CAS  PubMed  Google Scholar 

  40. Strahle, U., Fischer, N. & Blader, P. Expression and regulation of a netrin homologue in the zebrafish embryo. Mech. Dev. 62, 147–160 (1997).

    CAS  PubMed  Google Scholar 

  41. Altman, J. & Bayer, S. A. The development of the rat spinal cord. Adv. Anat. Embryol. Cell Biol. 85, 1–164 (1984).

    CAS  PubMed  Google Scholar 

  42. Kennedy, T. E., Serafini, T., de la Torre, J. R. & Tessier-Lavigne, M. Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 78, 425–435 (1994).

    CAS  PubMed  Google Scholar 

  43. MacLennan, A. J. et al. Immunohistochemical localization of netrin-1 in the embryonic chick nervous system. J. Neurosci. 17, 5466–5479 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Serafini, T. et al. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 78, 409–424 (1994).

    CAS  PubMed  Google Scholar 

  45. Ang, S. L. & Rossant, J. HNF-3β is essential for node and notochord formation in mouse development. Cell 78, 561–574 (1994).

    CAS  PubMed  Google Scholar 

  46. Weinstein, D. C. et al. The winged-helix transcription factor HNF-3β is required for notochord development in the mouse embryo. Cell 78, 575–588 (1994).

    CAS  PubMed  Google Scholar 

  47. Dodd, J., Jessell, T. M. & Placzek, M. The when and where of floor plate induction. Science 282, 1654–1657 (1998).

    CAS  PubMed  Google Scholar 

  48. Placzek, M., Dodd, J. & Jessell, T. M. Discussion point. The case for floor plate induction by the notochord. Curr. Opin. Neurobiol. 10, 15–22 (2000).

    CAS  PubMed  Google Scholar 

  49. Smith, J. L. & Schoenwolf, G. C. Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation. J. Exp. Zool. 250, 49–62 (1989).

    CAS  PubMed  Google Scholar 

  50. Yamada, T., Placzek, M., Tanaka, H., Dodd, J. & Jessell, T. M. Control of cell pattern in the developing nervous system: polarizing activity of the floor plate and notochord. Cell 64, 635–647 (1991).

    Article  CAS  PubMed  Google Scholar 

  51. van Straaten, H. W., Hekking, J. W., Wiertz-Hoessels, E. J., Thors, F. & Drukker, J. Effect of the notochord on the differentiation of a floor plate area in the neural tube of the chick embryo. Anat. Embryol. (Berl.) 177, 317–324 (1988).

    CAS  Google Scholar 

  52. Placzek, M., Tessier-Lavigne, M., Yamada, T., Jessell, T. & Dodd, J. Mesodermal control of neural cell identity: floor plate induction by the notochord. Science 250, 985–988 (1990).

    CAS  PubMed  Google Scholar 

  53. Baker, R. C. The early development of the ventral part of the neural plate of Amblystoma. J. Comp. Neurol. 44, 1–28 (1927).

    Google Scholar 

  54. Streeter, G. L. in Human Embryology. Vol. 2 (eds Keibel, F. & Mall, F. P.) 1–156 (1911).

    Google Scholar 

  55. Johnston, J. B. The morphology of the forebrain vesicle in vertebrates. J. Comp. Neurol. 29, 457–539 (1909).

    Google Scholar 

  56. Patten, I., Kulesa, P., Shen, M. M., Fraser, S. & Placzek, M. Distinct modes of floor plate induction in the chick embryo. Development 130, 4809–4821 (2003). Real-time fate mapping analysis in chick embryos shows that cells in area a and Hensen's node do not mix, that area a cells largely populate the anterior ventral midline and that they are induced by prechordal mesoderm.

    CAS  PubMed  Google Scholar 

  57. Strahle, U., Blader, P., Henrique, D. & Ingham, P. W. Axial, a zebrafish gene expressed along the developing body axis, shows altered expression in cyclops mutant embryos. Genes Dev. 7, 1436–1446 (1993).

    CAS  PubMed  Google Scholar 

  58. Chapman, S., Schubert, F., Schoenwolf, G. & Lumsden, A. Analysis of spatial and temporal gene expression patterns in blastula and gastrula stage chick embryos. Dev. Biol. 245, 187–199 (2002).

    CAS  PubMed  Google Scholar 

  59. Shen, M. M., Wang, H. & Leder, P. A differential display strategy identifies Cryptic, a novel EGF-related gene expressed in the axial and lateral mesoderm during mouse gastrulation. Development 124, 429–442 (1997).

    CAS  PubMed  Google Scholar 

  60. Mahmood, R., Kiefer, P., Guthrie, S., Dickson, C. & Mason, I. Multiple roles for FGF-3 during cranial neural development in the chicken. Development 121, 1399–1410 (1995).

    CAS  PubMed  Google Scholar 

  61. Ding, J. et al. Cripto is required for correct orientation of the anterior–posterior axis in the mouse embryo. Nature 395, 702–707 (1998).

    CAS  PubMed  Google Scholar 

  62. Colas, J. F. & Schoenwolf, G. C. Subtractive hybridization identifies chick-cripto, a novel EGF-CFC ortholog expressed during gastrulation, neurulation and early cardiogenesis. Gene 255, 205–217 (2000).

    CAS  PubMed  Google Scholar 

  63. Karabagli, H., Karabagli, P., Ladher, R. K. & Schoenwolf, G. C. Comparison of the expression patterns of several fibroblast growth factors during chick gastrulation and neurulation. Anat. Embryol. 205, 365–370 (2002).

    CAS  Google Scholar 

  64. Vesque, C. et al. Development of chick axial mesoderm: specification of prechordal mesoderm by anterior endoderm-derived TGFβ family signalling. Development 127, 2795–2809 (2000).

    CAS  PubMed  Google Scholar 

  65. Katsube, K. et al. The expression of chicken NOV, a member of the CCN gene family, in early stage development. Gene Expr. Patterns 1, 61–65 (2001).

    CAS  Google Scholar 

  66. Ruiz, J. C. & Robertson, E. J. The expression of the receptor-protein tyrosine kinase gene, eck, is highly restricted during early mouse development. Mech. Dev. 46, 87–100 (1994).

    CAS  PubMed  Google Scholar 

  67. Hynes, M. et al. Induction of midbrain dopaminergic neurons by Sonic hedgehog. Neuron 15, 35–44 (1995).

    CAS  PubMed  Google Scholar 

  68. Hynes, M., Poulsen, K., Tessier-Lavigne, M. & Rosenthal, A. Control of neuronal diversity by the floor plate: contact-mediated induction of midbrain dopaminergic neurons. Cell 80, 95–101 (1995).

    CAS  PubMed  Google Scholar 

  69. Roussa, E. & Krieglstein, K. Induction and specification of midbrain dopaminergic cells: focus on SHH, FGF8, and TGF-β. Cell Tissue Res. 318, 23–33 (2004).

    CAS  PubMed  Google Scholar 

  70. Yulis, C. R. & Munoz, R. I. Vertebrate floor plate transiently expresses a compound recognized by antisera raised against subcommissural organ secretion. Microsc. Res. Tech. 52, 608–614 (2001).

    CAS  PubMed  Google Scholar 

  71. del Brio, M. A., Riera, P., Munoz, R. I., Montecinos, H. & Rodriguez, E. M. The metencephalic floor plate of chick embryos expresses two secretory glycoproteins homologous with the two glycoproteins secreted by the subcommissural organ. Histochem. Cell Biol. 113, 415–426 (2000).

    CAS  PubMed  Google Scholar 

  72. Schoenwolf, G. C. & Sheard, P. Fate mapping the avian epiblast with focal injections of a fluorescent-histochemical marker: ectodermal derivatives. J. Exp. Zool. 255, 323–339 (1990). Fate mapping reveals that area a cells contribute to the floor plate of the early embryo and extend into the forebrain.

    CAS  PubMed  Google Scholar 

  73. Garcia, M. V., Alvarez, I. S. & Schoenwolf, G. C. Locations of the ectodermal and nonectodermal subdivisions of the epiblast at stages 3 and 4 of avian gastrulation and neurulation. J. Exp. Zool. 267, 431–446 (1993).

    Google Scholar 

  74. Selleck, M. A. J. & Stern, C. D. Fate mapping and cell lineage analysis of Hensen's node in the chick embryo. Development 112, 615–626 (1991).

    CAS  PubMed  Google Scholar 

  75. Schoenwolf, G. C., Bortier, H. & Vakaet, L. Fate mapping the avian neural plate with quail/chick chimeras: origin of prospective median wedge cells. J. Exp. Zool. 249, 271–278 (1989). Analysis of chick–quail chimaeras reveals that floor plate cells derive from area a — a region of epiblast just anterior to Hensen's node.

    CAS  PubMed  Google Scholar 

  76. Le Douarin, N. M. & Halpern, M. E. Discussion point. Origin and specification of the neural tube floor plate: insights from the chick and zebrafish. Curr. Opin. Neurobiol. 10, 23–30 (2000).

    CAS  PubMed  Google Scholar 

  77. van Straaten, H. W. & Hekking, J. W. Development of floor plate, neurons and axonal outgrowth pattern in the early spinal cord of the notochord-deficient chick embryo. Anat. Embryol. (Berl.) 184, 55–63 (1991).

    CAS  Google Scholar 

  78. Placzek, M., Jessell, T. M. & Dodd, J. Induction of floor plate differentiation by contact-dependent, homeogenetic signals. Development 117, 205–218 (1993).

    CAS  PubMed  Google Scholar 

  79. Muller, F. et al. Intronic enhancers control expression of zebrafish sonic hedgehog in floor plate and notochord. Development 126, 2103–2116 (1999).

    CAS  PubMed  Google Scholar 

  80. Kapsimali, M., Caneparo, L., Houart, C. & Wilson, S. W. Inhibition of Wnt/Axin/β-catenin pathway activity promotes ventral CNS midline tissue to adopt hypothalamic rather than floorplate identity. Development 131, 5923–5933 (2004). A study of the development of a hypothalamic ventral midline cell group that differentiates in the anterior forebrain around p3–p5. The analyses reveal that Wnt antagonists promote a p3–p5 hypothalamic floor plate fate, as opposed to a posterior floor plate fate.

    CAS  PubMed  Google Scholar 

  81. Etheridge, L. A., Wu, T., Liang, J. O., Ekker, S. C. & Halpern, M. E. Floor plate develops upon depletion of tiggy-winkle and sonic hedgehog. Genesis 30, 164–169 (2001).

    CAS  PubMed  Google Scholar 

  82. Tian, J. et al. A temperature-sensitive mutation in the nodal-related gene cyclops reveals that the floor plate is induced during gastrulation in zebrafish. Development 130, 3331–3342 (2003). Abrogation of Cyc/Nodal signalling in zebrafish embryos at various stages using a temperature-sensitive mutant indicates that the floor plate in zebrafish is induced during gastrulation. In addition, continuous Cyc signalling is required throughout gastrulation to produce a complete ventral neural tube throughout the length of the neuraxis.

    CAS  PubMed  Google Scholar 

  83. Odenthal, J. et al. Mutations affecting the formation of the notochord in the zebrafish, Danio rerio. Development 123, 103–115 (1996).

    CAS  PubMed  Google Scholar 

  84. Halpern, M. E. et al. Cell-autonomous shift from axial to paraxial mesodermal development in zebrafish floating head mutants. Development 121, 4257–4264 (1995).

    CAS  PubMed  Google Scholar 

  85. Halpern, M. E. et al. Genetic interactions in zebrafish midline development. Dev. Biol. 187, 154–170 (1997).

    CAS  PubMed  Google Scholar 

  86. Talbot, W. S. et al. A homeobox gene essential for zebrafish notochord development. Nature 378, 150–157 (1995).

    CAS  PubMed  Google Scholar 

  87. Beattie, C. E. et al. Temporal separation in the specification of primary and secondary motoneurons in zebrafish. Dev. Biol. 187, 171–182 (1997).

    CAS  PubMed  Google Scholar 

  88. Hatta, K., Kimmel, C. B., Ho, R. K. & Walker, C. The cyclops mutation blocks specification of the floor plate of the zebrafish central nervous system. Nature 350, 339–341 (1991). The first report that development of the floor plate fails in zebrafish embryos that bear the newly discovered zygotic lethal cyclops (nodal) mutation, cyc1 (b16).

    CAS  PubMed  Google Scholar 

  89. Zhang, J., Talbot, W. S. & Schier, A. F. Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation. Cell 92, 241–251 (1998).

    CAS  PubMed  Google Scholar 

  90. Strahle, U. et al. one-eyed pinhead is required for development of the ventral midline of the zebrafish (Danio rerio) neural tube. Genes Funct. 1, 131–148 (1997).

    CAS  PubMed  Google Scholar 

  91. Sirotkin, H. I., Gates, M. A., Kelly, P. D., Schier, A. F. & Talbot, W. S. Fast1 is required for the development of dorsal axial structures in zebrafish. Curr. Biol. 10, 1051–1054 (2000).

    CAS  PubMed  Google Scholar 

  92. Pogoda, H. M., Solnica-Krezel, L., Driever, W. & Meyer, D. The zebrafish forkhead transcription factor FoxH1/Fast1 is a modulator of Nodal signaling required for organizer formation. Curr. Biol. 10, 1041–1049 (2000).

    CAS  PubMed  Google Scholar 

  93. Sampath, K. et al. Induction of the zebrafish ventral brain and floorplate requires cyclops/nodal signalling. Nature 395, 185–189 (1998).

    CAS  PubMed  Google Scholar 

  94. Matise, M. P., Epstein, D. J., Park, H. L., Platt, K. A. & Joyner, A. L. Gli2 is required for induction of floor plate and adjacent cells, but not most ventral neurons in the mouse central nervous system. Development 125, 2759–2770 (1998). Analysis of a mouse that is mutant for the Gli2 gene, which codes for a crucial downstream component on the SHH signalling pathway, reveals that SHH signalling is required for the induction of floor plate cells from the spinal cord up to the midbrain/forebrain junction. These studies also show that GLI2 function is not required for the expression of FOXA1 and SHH in the more anterior forebrain. Motor neurons and ventral interneurons form in the mutant mouse.

    CAS  PubMed  Google Scholar 

  95. Ding, Q. et al. Diminished Sonic hedgehog signaling and lack of floor plate differentiation in Gli2 mutant mice. Development 125, 2533–2543 (1998). Similar to reference 94, these analyses show that GLI2 function is crucial for the development of floor plate cells that differentiate up to the midbrain, but is not required for the expression of FOXA1 and SHH in the forebrain. These analyses also reveal that motor neurons can differentiate in the absence of a floor plate, although note that the notochord stays in unusually close proximity to the ventral neural tube in Gli2 mutant mice.

    CAS  PubMed  Google Scholar 

  96. Motoyama, J. et al. Differential requirement for Gli2 and Gli3 in ventral neural cell fate specification. Dev. Biol. 259, 150–161 (2003).

    CAS  PubMed  Google Scholar 

  97. Chu, G. C., Dunn, N. R., Anderson, D. C., Oxburgh, L. & Robertson, E. J. Differential requirements for Smad4 in TGFβ-dependent patterning of the early mouse embryo. Development 131, 3501–3512 (2004).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  99. Jin, O., Harpal, K., Ang, S. L. & Rossant, J. Otx2 and HNF3β genetically interact in anterior patterning. Int. J. Dev. Biol. 45, 357–365 (2001).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  101. Varlet, I., Collignon, J., Norris, D. P. & Robertson, E. J. Nodal signaling and axis formation in the mouse. Cold Spring Harb. Symp. Quant. Biol. 62, 105–113 (1997).

    CAS  PubMed  Google Scholar 

  102. Catala, M., Teillet, M. A., De Robertis, E. M. & Le Douarin, M. L. A spinal cord fate map in the avian embryo: while regressing, Hensen's node lays down the notochord and floor plate thus joining the spinal cord lateral walls. Development 122, 2599–2610 (1996).

    CAS  PubMed  Google Scholar 

  103. Le Douarin, N. M. Teillet, M. A. & Catala, M. Neurulation in amniote vertebrates: a novel view deduced from the use of quail–chick chimeras. Int. J. Dev. Biol. 42, 909–916 (1998).

    CAS  PubMed  Google Scholar 

  104. Teillet, M. A., Lapointe, F. & Le Douarin, N. M. The relationships between notochord and floor plate in vertebrate development revisited. Proc. Natl Acad. Sci. USA 95, 11733–11738 (1998). Chick–quail chimaeras were used to follow the descendants of cells in the chordoneural hinge, a region of the embryo that links the regressing node and the forming notochord. The results provided evidence that some floor plate cells derive from the chordoneural hinge, resulting in the suggestion that floor plate cells are not induced by notochord, but are instead predetermined.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Artinger, K. B. & Bronner-Fraser, M. Delayed formation of the floor plate after ablation of the avian notochord. Neuron 11, 1147–1161 (1993).

    CAS  PubMed  Google Scholar 

  106. Chiang, C. et al. Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. Nature 383, 407–413 (1996).

    CAS  PubMed  Google Scholar 

  107. Wijgerde, M., McMahon, J. A., Rule, M. & McMahon, A. P. A direct requirement for Hedgehog signalling for normal specification of all ventral progenitor domains in the presumptive mammalian spinal cord. Genes Dev. 16, 2849–2864 (2002). The genetic removal of SMO, an obligate transducer of HH signalling, in mouse embryos reveals that HH signalling is required for floor plate specification.

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Incardona, J. P., Gaffield, W., Kapur, R. P. & Roelink, H. The teratogenic Veratrum alkaloid cyclopamine inhibits sonic hedgehog signal transduction. Development 125, 3553–3562 (1998). Evidence that in the chick, as in the mouse, SHH signalling is required for floor plate specification.

    CAS  PubMed  Google Scholar 

  109. Goodrich, L. V., Milenkovic, L., Higgins, K. M. & Scott, M. P. Altered neural cell fates and medulloblastoma in mouse patched mutants. Science 277, 1109–1113 (1997).

    CAS  PubMed  Google Scholar 

  110. Park, H. L. et al. Mouse Gli1 mutants are viable but have defects in SHH signaling in combination with a Gli2 mutation. Development 127, 1593–1605 (2000).

    CAS  PubMed  Google Scholar 

  111. Sasaki, H., Nishizaki, Y., Hui, C., Nakafuku, M. & Kondoh, H. Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development 126, 3915–3924 (1999).

    CAS  PubMed  Google Scholar 

  112. Sasaki, H., Hui, C., Nakafuku, M. & Kondoh, H. A binding site for Gli proteins is essential for HNF-3β floor plate enhancer activity in transgenics and can respond to Shh in vitro. Development 124, 1313–1322 (1997).

    CAS  PubMed  Google Scholar 

  113. Bai, C. B., Stephen, D. & Joyner, A. L. All mouse ventral spinal cord patterning by hedgehog is Gli dependent and involves an activator function of Gli3. Dev. Cell 6, 103–115 (2004).

    CAS  PubMed  Google Scholar 

  114. Roelink, H. et al. Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. Cell 81, 445–455 (1995).

    CAS  PubMed  Google Scholar 

  115. Dale, J. K. et al. Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm. Cell 90, 257–269 (1997).

    CAS  PubMed  Google Scholar 

  116. Hynes, M. et al. The seven-transmembrane receptor smoothened cell-autonomously induces multiple ventral cell types. Nature Neurosci. 1, 41–46 (2000).

    Google Scholar 

  117. Schauerte, H. E. et al. Sonic hedgehog is not required for the induction of medial floor plate cells in the zebrafish. Development 125, 2983–2993 (1998).

    CAS  PubMed  Google Scholar 

  118. Lewis, K. E. & Eisen, J. S. Hedgehog signaling is required for primary motoneuron induction in zebrafish. Development 128, 3485–3495 (2001).

    CAS  PubMed  Google Scholar 

  119. Chen, W., Burgess, S. & Hopkins, N. Analysis of the zebrafish smoothened mutant reveals conserved and divergent functions of hedgehog activity. Development 128, 2385–2396 (2001).

    CAS  PubMed  Google Scholar 

  120. Varga, Z. M. et al. Zebrafish smoothened functions in ventral neural tube specification and axon tract formation. Development 128, 3497–3509 (2001).

    CAS  PubMed  Google Scholar 

  121. Nakano, Y. et al. Inactivation of dispatched 1 by the chameleon mutation disrupts Hedgehog signalling in the zebrafish embryo. Dev. Biol. 269, 381–392 (2004).

    CAS  PubMed  Google Scholar 

  122. Karlstrom, R. O. et al. Genetic analysis of zebrafish gli1 and gli2 reveals divergent requirements for gli genes in vertebrate development. Development 130, 1549–1564 (2003). Analyses of zebrafish gli1 and gli2 mutants and morphants reveal divergent requirements for Gli1 and Gli2 in mouse and zebrafish. In addition, these studies indicate that depletion of Hh signalling does not completely eliminate Gli1 expression in zebrafish.

    CAS  PubMed  Google Scholar 

  123. Hatta, K. Role of the floor plate in axonal patterning in the zebrafish CNS. Neuron 9, 629–642 (1992).

    CAS  PubMed  Google Scholar 

  124. Rebagliati, M. R., Toyama, R., Haffter, P. & Dawid, I. B. cyclops encodes a nodal-related factor involved in midline signaling. Proc. Natl Acad. Sci. USA 95, 9932–9937 (1998).

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Mathieu, J., Barth, A., Rosa, F. M., Wilson, S. W. & Peyrieras, N. Distinct and cooperative roles for Nodal and Hedgehog signals during hypothalamic development. Development 129, 3055–3065 (2002). In zebrafish, maternal and zygotic removal of oep shows that Nodal signalling is required cell-autonomously for the differentiation of a set of forebrain (hypothalamic) ventral midline cells.

    CAS  PubMed  Google Scholar 

  126. Shinya, M., Furutani-Seiki, M., Kuroiwa, A. & Takeda, H. Mosaic analysis with oep mutant reveals a repressive interaction between floor-plate and non-floor-plate mutant cells in the zebrafish neural tube. Dev. Growth Differ. 41, 135–142 (1999).

    CAS  PubMed  Google Scholar 

  127. Muller, F. et al. Direct action of the nodal-related signal cyclops in induction of sonic hedgehog in the ventral midline of the CNS. Development 127, 3889–3897 (2000).

    CAS  PubMed  Google Scholar 

  128. Labbe, E., Silvestri, C., Hoodless, P. A., Wrana, J. L. & Attisano, L. Smad2 and Smad3 positively and negatively regulate TGFβ-dependent transcription through the forkhead DNA-binding protein FAST2. Mol. Cell 2, 109–120 (1998).

    CAS  PubMed  Google Scholar 

  129. Albert, S. et al. Cyclops-independent floor plate differentiation in zebrafish embryos. Dev. Dyn. 226, 59–66 (2003). One-day-old cyc mutant zebrafish embryos lack a floor plate, but in the hindbrain and spinal cord, floor plate cells are restored on embryonic day 2. This late differentiation depends on an intact Hh signalling pathway.

    PubMed  Google Scholar 

  130. Norton, W. H. et al. Monorail/Foxa2 regulates floor plate differentiation and specification of oligodendrocytes, serotonergic raphe neurones and cranial motoneurones. Development 132, 645–658 (2005).

    CAS  PubMed  Google Scholar 

  131. Heyer, J. et al. Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis. Proc. Natl Acad. Sci. USA 96, 12595–12600 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Nomura, M. & Li, E. Smad2 role in mesoderm formation, left–right patterning and craniofacial development. Nature 393, 786–790 (1998).

    CAS  PubMed  Google Scholar 

  133. Amacher, S. L., Draper, B. W., Summers, B. R. & Kimmel, C. B. The zebrafish T-box genes no tail and spadetail are required for development of trunk and tail mesoderm and medial floor plate. Development 129, 3311–3323 (2002).

    CAS  PubMed  Google Scholar 

  134. Woo, K. & Fraser, S. E. Order and coherence in the fate map of the zebrafish nervous system. Development 121, 2595–2609 (1995).

    CAS  PubMed  Google Scholar 

  135. Hynes, M. et al. Control of cell pattern in the neural tube by the zinc finger transcription factor and oncogene Gli-1. Neuron 19, 15–26 (1997).

    CAS  PubMed  Google Scholar 

  136. Sasaki, H. & Hogan, B. L. HNF-3β as a regulator of floor plate development. Cell 76, 103–115 (1994).

    CAS  PubMed  Google Scholar 

  137. Litingtung, Y. & Chiang, C. Control of Shh activity and signaling in the neural tube. Dev. Dyn. 219, 143–154 (2000).

    CAS  PubMed  Google Scholar 

  138. Lee, J., Platt, K. A., Censullo, P. & Ruiz i Altaba, A. Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. Development 124, 2537–2552 (1997).

    CAS  PubMed  Google Scholar 

  139. McMahon, J. A. et al. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 12, 1438–1452 (1998).

    CAS  PubMed Central  PubMed  Google Scholar 

  140. Patten, I. & Placzek, M. Opponent activities of Shh and BMP signaling during floor plate induction in vivo. Curr. Biol. 12, 47–52 (2002).

    CAS  PubMed  Google Scholar 

  141. Liem, K. F., Jessell, T. M. & Briscoe, J. Regulation of the neural patterning activity of sonic hedgehog by secreted BMP inhibitors expressed by notochord and somites. Development 127, 4855–4866 (2000).

    CAS  PubMed  Google Scholar 

  142. Jacob, J. & Briscoe, J. Gli proteins and the control of spinal-cord patterning. EMBO Rep. 4, 761–765 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  143. Liu, F., Massague, J. & Ruiz i Altaba, A. Carboxy-terminally truncated Gli3 proteins associate with Smads. Nature Genet. 20, 325–326 (1998).

    CAS  PubMed  Google Scholar 

  144. Yeo, C. & Whitman, M. Nodal signals to Smads through Cripto-dependent and Cripto-independent mechanisms. Mol. Cell 7, 949–957 (2001).

    CAS  PubMed  Google Scholar 

  145. Pinheiro, P., Gering, M. & Patient, R. The basic helix–loop–helix transcription factor, Tal2, marks the lateral floor plate of the spinal cord in zebrafish. Gene Expr. Patterns 4 85–92 (2004).

    CAS  PubMed  Google Scholar 

  146. Schafer, M. et al. Hedgehog and retinoid signalling confines nkx2.2b expression to the lateral floor plate of the zebrafish trunk. Mech. Dev. 122, 43–56 (2005).

    PubMed  Google Scholar 

  147. Barth, K. A. & Wilson, S. W. Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embyronic forebrain. Development 121, 1755–1768 (1995).

    CAS  PubMed  Google Scholar 

  148. Yuan, S. & Schoenwolf, G. C. de novo induction of the organiser and formation of the primitive streak in an experimental model of notochord reconstitution in avian embryos. Development 125, 201–213 (1998).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank D. Epstein, S. Amacher, E. Robertson and K. Lewis for helpful discussion, and A. Furley and E. Manning for help with figures.

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Authors and Affiliations

  1. Department of Biomedical Science, Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, S10 2TN, UK

    Marysia Placzek

  2. National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    James Briscoe

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Correspondence to Marysia Placzek.

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DATABASES

Entrez Gene

BMP7

chordin

cyc

disp1

ECK

ehh

flh

FOXA2

FOXH1

GLI2

GLI3

GSC

Nodal

noggin

NOV

ntl

oep

SHH

SMAD2

Smo

sur

twhh

Glossary

WNT PROTEINS

A family of highly conserved secreted signalling molecules that regulate cell–cell interactions during embryogenesis. WNT proteins bind at the cell surface to receptors of the Frizzled family.

BONE MORPHOGENETIC PROTEINS

(BMPs). Multifunctional secreted proteins of the transforming growth factor-β superfamily. In the early embryo, they participate in dorsoventral patterning.

NOTOCHORD

A rod-like structure of mesodermal origin that is found in vertebrate embryos. It derives from the node and participates in the differentiation of adjacent tissue, including the ventral neural tube.

PROSOMERES

Six subdivisions that are thought to compose the embryonic forebrain, and which are defined by their specific patterns of gene expression. Prosomeres 1–2 constitute the posterior diencephalon, caudal to the ZLI. Prosomeres 3–6 constitute the anterior diencephalon and telencephalon, including the hypothalamus.

ROSTROCAUDAL AXIS

(RC axis). During early stages of development, the neural tube is a straight structure with a clear anterior and posterior end. However, when the cephalic flexures form, the most anterior part of the neural tube bends over, so that technically, the most 'anterior' part is around the midbrain region. From this point in development, what was previously known as the anteroposterior axis is termed the rostrocaudal axis, with the forebrain representing the rostral-most point.

ZONA LIMITANS INTRATHALAMICA

(ZLI). An embryonic structure that determines the limit between the dorsal and ventral thalamus.

NODE

An important organizing centre in primitive-streak-stage embryos that regulates pattern formation. It is known as Hensen's node in the chick and as the Spemann organizer in the frog.

OPTIC CHIASM

The crossing point, in the base of the forebrain, for fibres from the two optic stalks that project to the opposite sides of the brain.

RECEPTOR TYROSINE KINASE

Any of a family of transmembrane receptors, the intracellular domains of which catalyse the phosphorylation, by ATP, of specific tyrosine residues on their target proteins.

EPIBLAST

The outer layer of a blastula, which gives rise to the ectoderm after gastrulation.

GASTRULATION

The process by which the embryo becomes regionalized into three layers: ectoderm, mesoderm and endoderm.

CIS-ACTING REGULATORY ELEMENTS

Regulatory genetic elements that are located in the same DNA molecule as the gene that is being regulated.

MORPHANT

Morphant technology is a method for inhibiting gene expression by using antisense oligonucleotides to block translation from specific mRNAs.

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Placzek, M., Briscoe, J. The floor plate: multiple cells, multiple signals. Nat Rev Neurosci 6, 230–240 (2005). https://doi.org/10.1038/nrn1628

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