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Progressive induction of caudal neural character by graded Wnt signaling

A Corrigendum to this article was published on 01 July 2002

This article has been updated

Abstract

Early in differentiation, all neural cells have a rostral character. Only later do posteriorly positioned neural cells acquire characteristics of caudal forebrain, midbrain and hindbrain cells. Caudalization of neural tissue in the chick embryo apparently involves the convergent actions of (i) fibroblast growth factor (FGF) signaling and (ii) signaling from the caudal paraxial mesoderm, or 'PMC activity', which has not yet been defined molecularly. Here we report evidence that Wnt signaling underlies PMC activity, and show that Wnt signals act directly and in a graded manner on anterior neural cells to induce their progressive differentiation into caudal forebrain, midbrain and hindbrain cells.

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Figure 1: Wnt11 and Wnt8c expression in the posterior region of the chick embryo at developmental stages when neural cell precursors are exposed to signals that induce caudal neural characters.
Figure 2: Wnt3A and FGF8 in combination induces the expression of Wnt8c in prospective rostral forebrain cells.
Figure 3: The induction of midbrain and hindbrain cells by caudal paraxial mesoderm requires Wnt signaling.
Figure 4: Ongoing Wnt signaling in neural plate cells is required for the acquisition of caudal forebrain but not rostral forebrain character.
Figure 5: Ongoing Wnt signaling in neural plate cells is required for the acquisition of midbrain and rostral hindbrain character.
Figure 6: Wnt signaling imposes rostrocaudal pattern on neural cells in intact chick embryos.
Figure 7: Graded Wnt3A activity, in combination with FGF8, induces caudal regional character in prospective rostral forebrain cells.

Change history

  • 11 June 2002

    Linked asterisk added to the phrase "rostral-to-caudal shift" -- the footnote reads: The authors wish to correct the phrase "rostral-to-caudal shift," which should read "rostrocaudal shift." An erratum will be published in the July issue.

Notes

  1. 1.

    NOTE: The authors wish to correct the phrase "rostral-to-caudal shift," which should read "rostrocaudal shift."

References

  1. 1

    Lumsden, A. & Krumlauf, R. Patterning the vertebrate neuraxis. Science 274, 1109–1115 (1996).

    CAS  PubMed  Google Scholar 

  2. 2

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

    CAS  PubMed  Google Scholar 

  3. 3

    Nieuwkoop, P. D. et al. Activation and organisation of the central nervous system in amphibians. J. Exp. Zool. 1–108 (1952).

  4. 4

    Muhr, J., Graziano, E., Wilson, S., Jessell, T. M. & Edlund, T. Convergent inductive signals specify midbrain, hindbrain and spinal cord identity in gastrula stage chick embryos. Neuron 23, 689–702 (1999).

    CAS  PubMed  Google Scholar 

  5. 5

    Muhr, J., Jessell, T. M. & Edlund, T. Assignment of early caudal identity to neural plate cells by a signal from caudal paraxial mesoderm. Neuron 19, 487–502 (1997).

    CAS  PubMed  Google Scholar 

  6. 6

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

    CAS  PubMed  Google Scholar 

  7. 7

    Domingos, P. M. et al. The Wnt/β-catenin pathway posteriorizes neural tissue in Xenopus by an indirect mechanism requiring FGF signaling. Dev. Biol. 239, 148–160 (2001).

    CAS  PubMed  Google Scholar 

  8. 8

    Maden, M. Heads or tails? Retinoic acid will decide. Bioessays 21, 809–812 (1999).

    CAS  PubMed  Google Scholar 

  9. 9

    Niederreither, K., Vermot, J., Schuhbaur, B., Chambon, P. & Dolle, P. Retinoic acid synthesis and hindbrain patterning in the mouse embryo. Development 127, 75–85 (2000).

    CAS  PubMed  Google Scholar 

  10. 10

    Liu, J. P., Laufer, E. & Jessell, T. M. Assigning the positional identity of spinal motor neurons. Rostrocaudal patterning of Hox-c expression by FGFs, Gdf11 and retinoids. Neuron 32, 997–1012 (2001).

    CAS  PubMed  Google Scholar 

  11. 11

    Woo, K. & Fraser, S. E. Specification of the zebrafish nervous system by nonaxial signals. Science 277, 254–257 (1997).

    CAS  PubMed  Google Scholar 

  12. 12

    Bang, A. G., Papalopulu, N., Kintner, C. & Goulding, M. D. Expression of Pax-3 is initiated in the early neural plate by posteriorizing signals produced by the organizer and by posterior non-axial mesoderm. Development 124, 2075–2085 (1997).

    CAS  PubMed  Google Scholar 

  13. 13

    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).

    CAS  PubMed  Google Scholar 

  14. 14

    Hume, C. R. & Dodd, J. Cwnt-8C: a novel Wnt gene with a potential role in primitive streak formation and hindbrain organization. Development 119, 1147–1160 (1993).

    CAS  PubMed  Google Scholar 

  15. 15

    Baranski, M., Berdougo, E., Sandler, J. S., Darnell, D. K. & Burrus, L. W. The dynamic expression pattern of frzb-1 suggests multiple roles in chick development. Dev. Biol. 217, 25–41 (2000).

    CAS  PubMed  Google Scholar 

  16. 16

    Yamaguchi, T. P. Heads or tails: Wnts and anterior-posterior patterning. Curr. Biol. 11, R713–724 (2001).

    Google Scholar 

  17. 17

    McGrew, L. L., Hoppler, S. & Moon, R. T. Wnt and FGF pathways cooperatively pattern anteroposterior neural ectoderm in Xenopus. Mech. Dev. 69, 105–114 (1997).

    CAS  PubMed  Google Scholar 

  18. 18

    Fredieu, J. R., Cui, Y., Maier, D., Danilchik, M. V. & Christian, J. L. Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos. Dev. Biol. 186, 100–114 (1997).

    CAS  PubMed  Google Scholar 

  19. 19

    Popperl, H. et al. Misexpression of Cwnt8C in the mouse induces an ectopic embryonic axis and causes a truncation of the anterior neuroectoderm. Development 124, 2997–3005 (1997).

    CAS  PubMed  Google Scholar 

  20. 20

    Bang, A.G., Papalopulu, N., Goulding, M.D. & Kintner, C. Expression of Pax-3 in the lateral neural plate is dependent on a Wnt-mediated signal from posterior nonaxial mesoderm. Dev. Biol. 212, 366–380 (1999).

    CAS  PubMed  Google Scholar 

  21. 21

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

    CAS  PubMed  Google Scholar 

  22. 22

    Huelsken, J. et al. Requirement for β-catenin in anterior-posterior axis formation in mice. J. Cell Biol. 148, 567–578 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Fekany-Lee, K., Gonzalez, E., Miller-Bertoglio, V. & Solnica-Krezel, L. The homeobox gene bozozok promotes anterior neuroectoderm formation in zebrafish through negative regulation of BMP2/4 and Wnt pathways. Development 127, 2333–2345 (2000).

    CAS  PubMed  Google Scholar 

  24. 24

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

    CAS  PubMed  Google Scholar 

  25. 25

    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).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

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

    CAS  PubMed  Google Scholar 

  27. 27

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

    CAS  PubMed  Google Scholar 

  28. 28

    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).

    CAS  PubMed  Google Scholar 

  29. 29

    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).

    CAS  PubMed  Google Scholar 

  30. 30

    Yoshikawa, Y., Fujimori, T., McMahon, A. P. & Takada, S. Evidence that absence of Wnt-3a signaling promotes neuralization instead of paraxial mesoderm development in the mouse. Dev. Biol. 183, 234–242 (1997).

    CAS  PubMed  Google Scholar 

  31. 31

    Takada, S. et al. Wnt-3a regulates somite and tailbud formation in the mouse embryo. Genes Dev. 8, 174–189 (1994).

    CAS  PubMed  Google Scholar 

  32. 32

    Eisenberg, C. A., Gourdie, R. G. & Eisenberg, L. M. Wnt-11 is expressed in early avian mesoderm and required for the differentiation of the quail mesoderm cell line QCE-6. Development 124, 525–536 (1997).

    CAS  PubMed  Google Scholar 

  33. 33

    Rex, M. et al. Dynamic expression of chicken Sox2 and Sox3 genes in ectoderm induced to form neural tissue. Dev. Dyn. 209, 323–332 (1997).

    CAS  PubMed  Google Scholar 

  34. 34

    Mallamaci, A., Di Blas, E., Briata, P., Boncinelli, E. & Corte, G. OTX2 homeoprotein in the developing central nervous system and migratory cells of the olfactory area. Mech. Dev. 58, 165–178 (1996).

    CAS  PubMed  Google Scholar 

  35. 35

    Bell, E., Ensini, M., Gulisano, M. & Lumsden, A. Dynamic domains of gene expression in the early avian forebrain. Dev. Biol. 236, 76–88 (2001).

    CAS  PubMed  Google Scholar 

  36. 36

    Matsunaga, E., Araki, I. & Nakamura, H. Pax6 defines the di-mesencephalic boundary by repressing En1 and Pax2. Development 127, 2357–2365 (2000).

    CAS  PubMed  Google Scholar 

  37. 37

    Davis, C. A. & Joyner, A. L. Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto-oncogene int-1 diverge during mouse development. Genes Dev. 2, 1736–1744 (1988).

    CAS  PubMed  Google Scholar 

  38. 38

    Shamim, H. & Mason, I. Expression of Gbx-2 during early development of the chick embryo. Mech. Dev. 76, 157–159 (1998).

    CAS  PubMed  Google Scholar 

  39. 39

    Nieto, M. A., Bradley, L. C. & Wilkinson, D. G. Conserved segmental expression of Krox-20 in the vertebrate hindbrain and its relationship to lineage restriction. Development Suppl. 2, 59–62 (1991).

  40. 40

    Hsieh, J. C., Rattner, A., Smallwood, P. M. & Nathans, J. Biochemical characterization of Wnt–frizzled interactions using a soluble, biologically active vertebrate Wnt protein. Proc. Natl. Acad. Sci. USA 96, 3546–3551 (1999).

    CAS  PubMed  Google Scholar 

  41. 41

    Wilson, S. et al. The status of Wnt signaling regulates neural and epidermal fates in the chick embryo. Nature 411, 325–330 (2001).

    CAS  PubMed  Google Scholar 

  42. 42

    New, D. A. A new technique for the cultivation of the chick embryo in vitro. J. Embryol. Exp. Morphol. 3, 320–331 (1955).

    Google Scholar 

  43. 43

    Shibamoto, S. et al. Cytoskeletal reorganization by soluble Wnt-3a protein signaling. Genes Cells 3, 659–670 (1998).

    CAS  PubMed  Google Scholar 

  44. 44

    Niehrs, C. Head in the WNT: the molecular nature of Spemann's head organizer. Trends Genet. 15, 314–319 (1999).

    CAS  PubMed  Google Scholar 

  45. 45

    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).

    CAS  PubMed  Google Scholar 

  46. 46

    Foley, A. C., Storey, K. G. & Stern, C. D. The prechordal region lacks neural inducing ability, but can confer anterior character to more posterior neuroepithelium. Development 124, 2983–2996 (1997).

    CAS  PubMed  Google Scholar 

  47. 47

    Gould, A., Itasaki, N. & Krumlauf, R. Initiation of rhombomeric Hoxb4 expression requires induction by somites and a retinoid pathway. Neuron 21, 39–51 (1998).

    CAS  PubMed  Google Scholar 

  48. 48

    Jessell, T. M. Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1, 20–29 (2000).

    CAS  PubMed  Google Scholar 

  49. 49

    Schaeren-Wiemers, N. & Gerfin-Moser, A. A single protocol to detect transcripts of various types and expression levels in neural tissue and cultured cells: in situ hybridization using digoxigenin-labelled cRNA probes. Histochemistry 100, 431–440 (1993).

    CAS  PubMed  Google Scholar 

  50. 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).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Y. Renoncourt for experimental contributions, members of the Edlund lab for discussions and H. Alstermark for technical assistance. We are grateful to R. Nusse for providing Wnt3A-expressing cells, to J. Nathans for the mFrzCRD-IgG plasmid and Xwnt8 cell line and to C. Tabin for Wnt probes. T.E. is supported by the Swedish Medical Research Council and by the Foundation for Strategic Research. T.M.J. is supported by grants from US National Institute of Neurological Disorders and Stroke (NIH-NINDS) and is an Investigator of the Howard Hughes Medical Institute.

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Correspondence to Thomas Edlund.

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Nordström, U., Jessell, T. & Edlund, T. Progressive induction of caudal neural character by graded Wnt signaling. Nat Neurosci 5, 525–532 (2002). https://doi.org/10.1038/nn0602-854

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