Letter | Published:

Evidence from cyclostomes for complex regionalization of the ancestral vertebrate brain

Nature volume 531, pages 97100 (03 March 2016) | Download Citation

Abstract

The vertebrate brain is highly complex, but its evolutionary origin remains elusive. Because of the absence of certain developmental domains generally marked by the expression of regulatory genes, the embryonic brain of the lamprey, a jawless vertebrate, had been regarded as representing a less complex, ancestral state of the vertebrate brain. Specifically, the absence of a Hedgehog- and Nkx2.1-positive domain in the lamprey subpallium was thought to be similar to mouse mutants in which the suppression of Nkx2-1 leads to a loss of the medial ganglionic eminence1,2. Here we show that the brain of the inshore hagfish (Eptatretus burgeri), another cyclostome group, develops domains equivalent to the medial ganglionic eminence and rhombic lip, resembling the gnathostome brain. Moreover, further investigation of lamprey larvae revealed that these domains are also present, ruling out the possibility of convergent evolution between hagfish and gnathostomes. Thus, brain regionalization as seen in crown gnathostomes is not an evolutionary innovation of this group, but dates back to the latest vertebrate ancestor before the divergence of cyclostomes and gnathostomes more than 500 million years ago.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Accessions

Primary accessions

Data deposits

The sequences of the genes described in this study have been deposited in the NCBI GenBank under accessions LC028239LC028243, LC028245 and KT897926KT897927 and KT897930KT897938.

References

  1. 1.

    , , & Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development 126, 3359–3370 (1999)

  2. 2.

    , , & Evolution of the brain developmental plan: insights from agnathans. Dev. Biol. 280, 249–259 (2005)

  3. 3.

    , , & The embryonic vertebrate forebrain: the prosomeric model. Science 266, 578–580 (1994)

  4. 4.

    , & The Mouse Nervous System (Academic Press, 2011)

  5. 5.

    Insights into cyclostome phylogenomics: pre-2R or post-2R? Zoolog. Sci. 25, 960–968 (2008)

  6. 6.

    , & The Central Nervous System of Vertebrates (Springer, 1998)

  7. 7.

    , , & Evolution of the regionalization and patterning of the vertebrate telencephalon: what can we learn from cyclostomes? Curr. Opin. Genet. Dev. 23, 475–483 (2013)

  8. 8.

    & A long, remarkable journey: tangential migration in the telencephalon. Nature Rev. Neurosci. 2, 780–790 (2001)

  9. 9.

    , , , & Development and organization of the lamprey telencephalon with special reference to the GABAergic system. Front. Neuroanat. 5, 20 (2011)

  10. 10.

    , , , & Evolutionary conservation of the basal ganglia as a common vertebrate mechanism for action selection. Curr. Biol. 21, 1081–1091 (2011)

  11. 11.

    & The forebrain of the Pacific hagfish: a cladistic reconstruction of the ancestral craniate forebrain. Brain Behav. Evol. 40, 25–64 (1992)

  12. 12.

    & An immunohistochemical study of the telencephalon and the diencephalon in a myxinoid jawless fish, the Pacific hagfish, Eptatretus stouti. Brain Behav. Evol. 43, 140–161 (1994)

  13. 13.

    The Comparative Anatomy and Histology of the Cerebellum. (Univ. Minnesota Press 1967)

  14. 14.

    The development of the brain of Bdellostoma stouti 1. External growth changes. J. Comp. Neurol. 47, 343–403 (1929)

  15. 15.

    Studien zur vergleichenden Entwicklungsgeschichte des Kopfes der Kranioten, Heft 4: Zur Kopfentwicklung von Bdellostoma (Lehmann, 1900)

  16. 16.

    , & Hagfish embryology with reference to the evolution of the neural crest. Nature 446, 672–675 (2007)

  17. 17.

    On the Embryology of Bdellostoma stouti: a General Account of Myxinoid Development from the Egg and Segmentation to Hatching 220–276 (Harvard Univ., 1899)

  18. 18.

    , , , & Craniofacial development of hagfishes and the evolution of vertebrates. Nature 493, 175–180 (2013)

  19. 19.

    , , , & The early scaffold of axon tracts in the brain of a primitive vertebrate, the sea lamprey. Brain Res. Bull. 75, 42–52 (2008)

  20. 20.

    , , & New and old thoughts on the segmental organization of the forebrain in lampreys. Brain Behav. Evol. 74, 7–19 (2009)

  21. 21.

    et al. Patterns and consequences of vertebrate Emx gene duplications. Evol. Dev. 11, 343–353 (2009)

  22. 22.

    & The genetics of early telencephalon patterning: some assembly required. Nature Rev. Neurosci. 9, 678–685 (2008)

  23. 23.

    & A new scenario of hypothalamic organization: rationale of new hypotheses introduced in the updated prosomeric model. Front. Neuroanat. 9, 27 (2015)

  24. 24.

    & The role of organizers in patterning the nervous system. Annu. Rev. Neurosci. 35, 347–367 (2012)

  25. 25.

    et al. Involvement of Hedgehog and FGF signalling in the lamprey telencephalon: evolution of regionalization and dorsoventral patterning of the vertebrate forebrain. Development 138, 1217–1226 (2011)

  26. 26.

    , , & Role of Pax6 in development of the cerebellar system. Development 126, 3585–3596 (1999)

  27. 27.

    et al. The long adventurous journey of rhombic lip cells in jawed vertebrates: a comparative developmental analysis. Front. Neuroanat. 5, 27 (2011)

  28. 28.

    et al. Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). Proc. Natl Acad. Sci. USA 110, 16044–16049 (2013)

  29. 29.

    , & Evolution of the vertebrate Pax4/6 class of genes with focus on its novel member, the Pax10 gene. Genome Biol. Evol. 6, 1635–1651 (2014)

  30. 30.

    The Downtonian and Devonian Vertebrates of Spitsbergen: Part 1, Family Cephalaspidae (I kommisjon hos J. Dybwad, 1927)

  31. 31.

    , , & in In Situ Hybridization Methods (ed. ), Ch. 12, 249–262 (Springer, 2015)

  32. 32.

    , & Gene expression analysis of lamprey embryos. In: In Situ Hybridization Methods (ed. ), 263–278 (Springer, 2015)

  33. 33.

    Normal stages of development in the lamprey, Lampetra reissneri (Dybowski). Zoolog. Sci. 5, 109–118 (1988)

  34. 34.

    , & A series of normal stages for development of Scyliorhinus canicula, the lesser spotted dogfish (Chondrichthyes, Scyliorhinidae). J. Exp. Zool. 267, 318–336 (1993)

  35. 35.

    et al. Overview of the transcriptome profiles identified in hagfish, shark, and bichir: current issues arising from some nonmodel vertebrate taxa. J. Exp. Zool. B Mol. Dev. Evol . 316, 526–546 (2011)

  36. 36.

    , , , & Expression of thyroid transcription factor-1 (TTF-1) gene in the ventral forebrain and endostyle of the agnathan vertebrate, Lampetra japonica. Genesis 30, 51–58 (2001)

  37. 37.

    & Using GeneWise in the Drosophila annotation experiment. Genome Res. 10, 547–548 (2000)

  38. 38.

    & Prediction of complete gene structures in human genomic DNA. J. Mol. Biol. 268, 78–94 (1997)

  39. 39.

    et al. Identification of Cis-regulatory elements in the mouse Pax9/Nkx2-9 genomic region: implication for evolutionary conserved synteny. Genetics 165, 235–242 (2003)

  40. 40.

    et al. Structural evolution of Otx genes in craniates. Mol. Biol. Evol. 18, 1668–1678 (2001)

  41. 41.

    , , & Development of the head and trunk mesoderm in the dogfish, Scyliorhinus torazame: II. Comparison of gene expression between the head mesoderm and somites with reference to the origin of the vertebrate head. Evol. Dev. 14, 257–276 (2012)

  42. 42.

    , , , & The Dlx genes as clues to vertebrate genomics and craniofacial evolution. Semin. Cell Dev. Biol. 24, 110–118 (2013)

  43. 43.

    , & Reevaluating Emx gene phylogeny: homopolymeric amino acid tracts as a potential factor obscuring orthology signals in cyclostome genes. BMC Evol. Biol. 15, 78 (2015)

  44. 44.

    et al. The fifth neurohypophysial hormone receptor is structurally related to the V2-type receptor but functionally similar to V1-type receptors. Gen. Comp. Endocrinol. 178, 519–528 (2012)

  45. 45.

    in Handbuch der Vergleichenden und Experimentellen Entwicklungslehre der Wirbeltiere Vol. 2 (ed. ) 1–272 (G. Fischer, 1906)

  46. 46.

    The development of the brain of Bdellostoma stouti. II. Internal growth changes. J. Comp. Neurol. 52, 365–499 (1931)

  47. 47.

    & nkx2.1 and nkx2.4 genes function partially redundant during development of the zebrafish hypothalamus, preoptic region, and pallidum. Front. Neuroanat. 8, 145 (2014)

Download references

Acknowledgements

We thank O. Kakitani for hagfish sampling; K. Shirato for shark sampling; S. Shibuya, K. Yamamoto and Y. Yamamoto for maintenance of aquarium tanks; D. Sipp for critical reading of this manuscript; C. Mitgutsch and M. Kawaguchi for discussions; K. G. Ota and I. Sato for technical support; and H. Nagashima for lamprey sampling and discussions. This research was supported by direct budget supplied by Centre for Developmental Biology, RIKEN, JSPS KAKENHI grant numbers 15H02416 and 25840133, and by Hyogo Science and Technology Association.

Author information

Affiliations

  1. Evolutionary Morphology Laboratory, RIKEN, Kobe 650-0047, Japan

    • Fumiaki Sugahara
    • , Juan Pascual-Anaya
    • , Shin-ichi Aota
    • , Wataru Takagi
    • , Tamami Hirai
    •  & Shigeru Kuratani
  2. Division of Biology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan

    • Fumiaki Sugahara
  3. Development and Function of Inhibitory Neural Circuits, Max Planck Florida Institute for Neuroscience, Jupiter, Florida 33458, USA

    • Yasuhiro Oisi
  4. Phyloinformatics Unit, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan

    • Shigehiro Kuraku
  5. Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA

    • Noritaka Adachi
  6. Division of Gross Anatomy and Morphogenesis, Niigata University Graduate School of Medical and Dental Sciences, Niigata 950-8510, Japan

    • Noboru Sato
  7. Graduate School of Science and Engineering, Ehime University, Matsuyama 790-8577, Japan

    • Yasunori Murakami

Authors

  1. Search for Fumiaki Sugahara in:

  2. Search for Juan Pascual-Anaya in:

  3. Search for Yasuhiro Oisi in:

  4. Search for Shigehiro Kuraku in:

  5. Search for Shin-ichi Aota in:

  6. Search for Noritaka Adachi in:

  7. Search for Wataru Takagi in:

  8. Search for Tamami Hirai in:

  9. Search for Noboru Sato in:

  10. Search for Yasunori Murakami in:

  11. Search for Shigeru Kuratani in:

Contributions

F.S., J.P.-A., Y.M. and S. Kuratani designed the experiments and wrote the paper. F.S., J.P.-A., Y.O., S.A., N.A. and T.H. performed molecular works. N.S. discussed and interpreted the data. S. Kuraku performed the molecular phylogenetic analysis. W.T. performed the Nkx2.1/2.4 locus synteny conservation analysis.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Shigeru Kuratani.

Extended data

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature16518

Further reading

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.

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