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.

  • Letter
  • Published:

Initiation of neural induction by FGF signalling before gastrulation

Nature volume 406, pages 74–78 (2000)Cite this article

Abstract

During neural induction, the ‘organizer’ of the vertebrate embryo instructs neighbouring ectodermal cells to become nervous system rather than epidermis. This process is generally thought to occur around the mid-gastrula stage of embryogenesis1. Here we report the isolation of ERNI, an early response gene to signals from the organizer (Hensen's node). Using ERNI as a marker, we present evidence that neural induction begins before gastrulation—much earlier in development than previously thought. We show that the organizer and some of its precursor cells produce a fibroblast growth factor signal, which can initiate, and is required for, neural induction.

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: Structure and cellular localization of ERNI.
Figure 2: cERNI expression in the neural plate and its induction by Hensen's node and FGF8.
Figure 3: FGF signalling is an essential component of the neural induction pathway.
Figure 4: Organizer precursor cells initiate the neural induction cascade.

Similar content being viewed by others

References

  1. Harland, R. & Gerhart, J. Formation and function of Spemann's organizer. Annu. Rev. Cell Dev. Biol. 13, 611–667 (1997).

    Article  CAS  Google Scholar 

  2. Wilson, P. A. & Hemmati-Brivanlou, A. Vertebrate neural induction: inducers, inhibitors, and a new synthesis. Neuron 18 , 699–710 (1997).

    Article  CAS  Google Scholar 

  3. Schier, A. F. & Talbot, W. S. The zebrafish organizer. Curr. Opin. Genet. Dev. 8, 464–471 (1998).

    Article  CAS  Google Scholar 

  4. 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).

    CAS  PubMed  Google Scholar 

  5. Baker, J. C., Beddington, R. S. & Harland, R. M. Wnt signaling in Xenopus embryo inhibits BMP4 expression and activates neural development. Genes Dev. 13, 3149–3159 (1999).

    Article  CAS  Google Scholar 

  6. Klingensmith, J., Ang, S. L., Bachiller, D. & Rossant, J. Neural induction and patterning in the mouse in the absence of the node and its derivatives. Dev. Biol. 216, 535– 549 (1999).

    Article  Google Scholar 

  7. Streit, A. & Stern, C. D. Neural induction. A bird's eye view. Trends Genet. 15, 20– 24 (1999).

    Article  CAS  Google Scholar 

  8. Gurdon, J. B. Embryonic induction—molecular prospects. Development 99, 285–306 (1987).

    CAS  PubMed  Google Scholar 

  9. Streit, A. et al. Preventing the loss of competence for neural induction: HGF/SF, L5 and Sox-2. Development 124, 119– 1202 (1997).

    Google Scholar 

  10. Hatada, Y. & Stern, C. D. A fate map of the epiblast of the early chick embryo. Development 120, 2879 –2889 (1994).

    CAS  PubMed  Google Scholar 

  11. Garcia-Martinez, 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).

    Article  CAS  Google Scholar 

  12. Streit, A. & Stern, C. D. Establishment and maintenance of the border of the neural plate in the chick: involvement of FGF and BMP activity. Mech. Dev. 82, 51–66 (1999).

    Article  CAS  Google Scholar 

  13. Chambers, D. & Mason, I. Expression of sprouty-2 during early development of the chick embryo is coincident with known sites of FGF signalling. Mech. Dev. 91, 361–364 (2000).

    Article  CAS  Google Scholar 

  14. 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 

  15. Mohammadi, M. et al. Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276, 955–960 (1997).

    Article  CAS  Google Scholar 

  16. Ye, W., Shimamura, K., Rubenstein, J. L., Hynes, M. A. & Rosenthal, A. FGF and Shh signals control dopaminergic and serotonergic cell fate in the anterior neural plate. Cell 93, 755–659 (1993).

    Article  Google Scholar 

  17. Izpisua-Belmonte, J. C., De Robertis, E. M., Storey, K. G. & Stern, C. D. The homeobox gene goosecoid and the origin of organizer cells in the early chick blastoderm. Cell 74, 645– 659 (1993).

    Article  CAS  Google Scholar 

  18. Launay, C., Fromentoux, V., Shi, D. L. & Boucaut, J. C. A truncated FGF receptor blocks neural induction by endogenous Xenopus inducers. Development 122, 869– 880 (1996).

    CAS  Google Scholar 

  19. Sasai, Y., Lu, B., Piccolo, S. & De Robertis, E. M. Endoderm induction by the organizer-secreted factors chordin and noggin in Xenopus animal caps. EMBO J. 15, 4547– 4555 (1996).

    Article  CAS  Google Scholar 

  20. Amaya, E., Musci, T. J. & Kirschner, M. W. Expression of a dominant negative mutant of the FGF receptor disrupts mesoderm formation in Xenopus embryos. Cell 66, 257–270 ( 1991).

    Article  CAS  Google Scholar 

  21. Lamb, T. M. & Harland, R. M. Fibroblast growth factor is a direct neural inducer, which combined with noggin generates anterior–posterior neural pattern. Development 121, 3627– 3636 (1995).

    CAS  Google Scholar 

  22. 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  Google Scholar 

  23. Hongo, I., Kengaku, M. & Okamoto, H. FGF signaling and the anterior neural induction in Xenopus. Dev. Biol. 216, 561– 581 (1999).

    Article  CAS  Google Scholar 

  24. Biehs, B., Francois, V. & Bier, E. The Drosophila short gastrulation gene prevents Dpp from autoactivating and suppressing neurogenesis in the neuroectoderm. Genes Dev. 10, 2922–2934 (1996).

    Article  CAS  Google Scholar 

  25. Dulac, C. & Axel, R. A novel family of genes encoding putative pheromone receptors in mammals. Cell 83, 195–206 (1995).

    Article  CAS  Google Scholar 

  26. Eyal-Giladi, H. & Kochav, S. From cleavage to primitive streak formation: a complementary normal table and a new look at the first stages of the development of the chick. I. General morphology. Dev. Biol. 49, 321–337 ( 1976).

    Article  CAS  Google Scholar 

  27. Hamburger, V. & Hamilton, H. L. A series of normal stages in the development of the chick embryo. J. Morphol. 88 , 49–92 (1951).

    Article  CAS  Google Scholar 

  28. Stern, C. D. & Ireland, G. W. An integrated experimental study of endoderm formation in avian embryos. Anat. Embryol. 163, 245–263 (1981).

    Article  CAS  Google Scholar 

  29. Streit, A. & Stern, C. D. Mesoderm patterning and somite formation during node regression: differential effects of chordin and noggin. Mech. Dev. 85, 85–96 (1999).

    Article  CAS  Google Scholar 

  30. Stern, C. D. Detection of multiple gene products simultaneously by in situ hybridization and immunohistochemistry in whole mounts of avian embryos. Curr. Top. Dev. Biol. 36, 223–243 (1998).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Rosenthal and W. Ye (Genentech) for the FGFR1-IgG construct; R. Lovell-Badge for Sox3 and Sox2 and T. Jessell for S17; C. Dulac for advice on the differential screen; B. Cigich for technical assistance; I. Skromne for Fig. 4b, c; C. Ang for zebrafinch tissue; and T. Jessell, G. Sheng, K. Storey and D. Vasiliauskas for helpful comments on the manuscript. Supported by the National Institute of Mental Health.

Author information

Author notes

  1. Claudio D. Stern: Correspondence and requests for materials should be addressed to C.D.S.

Authors and Affiliations

  1. Department of Genetics and Development,

    Andrea Streit, Costis Papanayotou, Andrés Sirulnik & Claudio D. Stern

  2. Center for Neurobiology and Behavior, Columbia University, 701 West 168th Street #1602, New York, 10032, New York, USA

    Alyson J. Berliner & Claudio D. Stern

Authors
  1. Andrea Streit
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alyson J. Berliner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Costis Papanayotou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Andrés Sirulnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Claudio D. Stern
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Streit, A., Berliner, A., Papanayotou, C. et al. Initiation of neural induction by FGF signalling before gastrulation . Nature 406, 74–78 (2000). https://doi.org/10.1038/35017617

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/35017617

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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