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:

Hagfish embryology with reference to the evolution of the neural crest

Abstract

Hagfish, which lack both jaws and vertebrae, have long been the subject of intense interest owing to their position at a crucial point in the evolutionary transition to a truly vertebrate body plan1,2,3,4. However, unlike the comparatively well characterized vertebrate agnathan lamprey, little is known about hagfish development. The inability to analyse hagfish at early embryonic stages has frustrated attempts to resolve questions with important phylogenetic implications, including fundamental ones relating to the emergence of the neural crest1,5,6. Here we report the obtainment of multiple pharyngula-stage embryos of the hagfish species Eptatretus burgeri and our preliminary analyses of their early development. We present histological evidence of putative neural crest cells, which appear as delaminated cells that migrate along pathways corresponding to neural crest cells in fish and amphibians2,7,8,9,10,11. Molecular cloning studies further revealed the expression of several regulatory genes, including cognates of Pax6, Pax3/7, SoxEa and Sox9, suggesting that the hagfish neural crest is specified by molecular mechanisms that are general to vertebrates. We propose that the neural crest emerged as a population of de-epithelialized migratory cells in a common vertebrate ancestor, and suggest that the possibility of classical and molecular embryology in hagfish opens up new approaches to clarifying the evolutionary history of vertebrates.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Evolution of vertebrates and neural crest.
Figure 2: Embryos of Eptatretus burgeri.
Figure 3: Neural crest cells in E. burgeri.
Figure 4: Sox9 expression in the neural crest of E. burgeri.

Similar content being viewed by others

References

  1. Janvier, P. Early Vertebrates (Oxford Univ. Press, Oxford, 1996)

    Google Scholar 

  2. Hall, B. K. The Neural Crest in Development and Evolution (Springer, New York, 1999)

    Book  Google Scholar 

  3. Wicht, H. & Northcutt, R. G. Ontogeny of the head of the Pacific hagfish (Eptatretus stouti, Myxinoidea): development of the lateral line system. Phil. Trans. R. Soc. Lond. B 349, 119–134 (1995)

    Article  ADS  CAS  Google Scholar 

  4. Ota, K. G. & Kuratani, S. The history of scientific endeavors towards understanding hagfish embryology. Zoolog. Sci. 23, 403–418 (2006)

    Article  Google Scholar 

  5. Holmgren, N. On two embryos of Myxine glutinosa. Acta Zoologica 27, 1–90 (1946)

    Article  Google Scholar 

  6. Løvtrup, S. The Phylogeny of Vertebrata (Wiley, New York, 1977)

    Google Scholar 

  7. Bronner-Fraser, M. Environmental influences on neural crest cell migration. J. Neurobiol. 24, 233–247 (1993)

    Article  CAS  Google Scholar 

  8. Collazo, A., Bronner-Fraser, M. & Fraser, S. E. Vital dye labelling of Xenopus laevis trunk neural crest reveals multipotency and novel pathways of migration. Development 118, 363–376 (1993)

    CAS  PubMed  Google Scholar 

  9. Eisen, J. S. & Weston, J. A. Development of the neural crest in the zebrafish. Dev. Biol. 159, 50–59 (1993)

    Article  CAS  Google Scholar 

  10. McCauley, D. W. & Bronner-Fraser, M. Neural crest contributions to the lamprey head. Development 130, 2317–2327 (2003)

    Article  CAS  Google Scholar 

  11. Le Douarin, N. & Kalcheim, C. The Neural Crest (Cambridge Univ. Press, Cambridge, 1999)

    Book  Google Scholar 

  12. Gorbman, A. Hagfish development. Zoolog. Sci. 14, 375–390 (1997)

    Article  Google Scholar 

  13. Dean, B. On the embryology of Bdellostoma stouti. A general account of myxinoid development from the egg and segmentation to hatching. In Festschrift zum 70ten Geburststag Carl von Kupffer 220–276 (Gustav Fischer, Jena, 1899)

    Google Scholar 

  14. Gans, C. & Northcutt, R. G. Neural crest and the origin of vertebrates: A new head. Science 220, 268–274 (1983)

    Article  ADS  CAS  Google Scholar 

  15. Wicht, H. & Tusch, U. in The Biology of Hagfish (eds Jørgensen, J. M., Lomholt, J. R., Weber, R. E. & Malte, H.) 431–451 (Chapman & Hall, London, 1998)

    Book  Google Scholar 

  16. Conel, J. L. The origin of the neural crest. J. Comp. Neurol. 76, 191–215 (1942)

    Article  Google Scholar 

  17. Mallatt, J. & Sullivan, J. 28S and 18S rDNA sequences support the monophyly of lampreys and hagfishes. Mol. Biol. Evol. 15, 1706–1718 (1998)

    Article  CAS  Google Scholar 

  18. Takezaki, N., Figueroa, F., Zaleska-Rutczynska, Z. & Klein, J. Molecular phylogeny of early vertebrates: monophyly of the agnathans as revealed by sequences of 35 genes. Mol. Biol. Evol. 20, 287–292 (2003)

    Article  CAS  Google Scholar 

  19. Furlong, R. F. & Holland, P. W. Bayesian phylogenetic analysis supports monophyly of ambulacraria and of cyclostomes. Zoolog. Sci. 19, 593–599 (2002)

    Article  Google Scholar 

  20. Goodrich, E. S. Studies on the Structure and Development of Vertebrates (McMillan, London, 1930)

    Book  Google Scholar 

  21. Callaerts, P., Halder, G. & Gehring, W. J. PAX-6 in development and evolution. Annu. Rev. Neurosci. 20, 483–532 (1997)

    Article  CAS  Google Scholar 

  22. Goulding, M. D., Chalepakis, G., Deutsch, U., Erselius, J. R. & Gruss, P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J. 10, 1135–1147 (1991)

    Article  CAS  Google Scholar 

  23. Cheung, M. & Briscoe, J. Neural crest development is regulated by the transcription factor Sox9. Development 130, 5681–5693 (2003)

    Article  CAS  Google Scholar 

  24. McCauley, D. W. & Bronner-Fraser, M. Importance of SoxE in neural crest development and the evolution of the pharynx. Nature 441, 750–752 (2006)

    Article  ADS  CAS  Google Scholar 

  25. Nieto, M. A., Sargent, M. G., Wilkinson, D. G. & Cooke, J. Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Science 264, 835–839 (1994)

    Article  ADS  CAS  Google Scholar 

  26. Locascio, A., Manzanares, M., Blanco, M. J. & Nieto, M. A. Modularity and reshuffling of Snail and Slug expression during vertebrate evolution. Proc. Natl Acad. Sci. USA 99, 16841–16846 (2002)

    Article  ADS  CAS  Google Scholar 

  27. Jeffery, W. R., Strickler, A. G. & Yamamoto, Y. Migratory neural crest-like cells form body pigmentation in a urochordate embryo. Nature 431, 696–699 (2004)

    Article  ADS  CAS  Google Scholar 

  28. Shu, D. G. et al. Head and backbone of the Early Cambrian vertebrate Haikouichthys. Nature 421, 526–529 (2003)

    Article  ADS  CAS  Google Scholar 

  29. Kumar, S. & Hedges, S. B. A molecular timescale for vertebrate evolution. Nature 392, 917–920 (1998)

    Article  ADS  CAS  Google Scholar 

  30. Gorbman, A. & Tamarin, A. Early development of oral, olfactory and adenohypophyseal structures of agnathans and its evolutionary implications. In Evolutionary Biology of Primitive Fishes (eds Foreman, R. E., Gorbman, A., Dodd, J. M. and Olsson, R.) 165–185 (Plenum, New York, 1985)

    Chapter  Google Scholar 

Download references

Acknowledgements

We thank O. Kakitani for the sample collection, H. Nagashima and Y. K. Ohya for technical advice, and R. Ladher and D. Sipp for critical reading of this manuscript. This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author Contributions K.G.O. performed sample collection, maintenance of the aquarium tank, molecular cloning and in situ hybridization. S. Kuraku was particularly engaged in isolation of Snail family genes and performed phylogenetic analyses. S. Kuratani operated on the hagfish embryos and conducted histological analysis. K.G.O. and S. Kuratani wrote the manuscript. All of the authors discussed the results and commented on the manuscript.

Sequences for Pax6, Pax3/7, Snail, SoxEa and Sox9 from E. burgeri are deposited in DNA Data Bank of Japan (DDBJ) under accession numbers AB270704, AB270703, AB288229, AB288230 and AB270702, respectively.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shigeru Kuratani.

Ethics declarations

Competing interests

Sequences for Pax6, Pax3/7, Snail, SoxEa and Sox9 from E. burgeri are deposited in DNA Data Bank of Japan (DDBJ) under accession numbers AB270704, AB270703, AB288229, AB288230 and AB270702, respectively. Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Methods, Supplementary Figures 1-6 and Supplementary Table1. (PDF 736 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ota, K., Kuraku, S. & Kuratani, S. Hagfish embryology with reference to the evolution of the neural crest. Nature 446, 672–675 (2007). https://doi.org/10.1038/nature05633

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05633

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

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