Skip to main content

Thank you for visiting 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.

Unexpected complexity of the Wnt gene family in a sea anemone


The Wnt gene family encodes secreted signalling molecules that control cell fate in animal development and human diseases1. Despite its significance, the evolution of this metazoan-specific protein family is unclear. In vertebrates, twelve Wnt subfamilies were defined, of which only six have counterparts in Ecdysozoa (for example, Drosophila and Caenorhabditis)2. Here, we report the isolation of twelve Wnt genes from the sea anemone Nematostella vectensis3, a species representing the basal group4 within cnidarians. Cnidarians are diploblastic animals and the sister-group to bilaterian metazoans5. Phylogenetic analyses of N. vectensis Wnt genes reveal a thus far unpredicted ancestral diversity within the Wnt family2,6,7. Cnidarians and bilaterians have at least eleven of the twelve known Wnt gene subfamilies in common; five subfamilies appear to be lost in the protostome lineage. Expression patterns of Wnt genes during N. vectensis embryogenesis indicate distinct roles of Wnts in gastrulation, resulting in serial overlapping expression domains along the primary axis of the planula larva. This unexpectedly complex inventory of Wnt family signalling factors evolved in early multi-cellular animals about 650 million years (Myr) ago, predating the Cambrian explosion by at least 100 Myr (refs 5, 8). It emphasizes the crucial function of Wnt genes in the diversification of eumetazoan body plans9.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Bayesian inference consensus tree of the Wnt gene family.
Figure 2: Expression of N. vectensis Wnt genes during embryogenesis.
Figure 3: Overlapping expression domains of Wnt genes in a N. vectensis planula.


  1. Nelson, W. J. & Nusse, R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303, 1483–1487 (2004)

    ADS  CAS  Article  Google Scholar 

  2. Prud'homme, B., Lartillot, N., Balavoine, G., Adoutte, A. & Vervoort, M. Phylogenetic analysis of the Wnt gene family. Insights from lophotrochozoan members. Curr. Biol. 12, 1395–1400 (2002)

    CAS  Article  Google Scholar 

  3. Ball, E. E., Hayward, D. C., Saint, R. & Miller, D. J. A simple plan—cnidarians and the origins of developmental mechanisms. Nature Rev. Genet. 5, 567–577 (2004)

    CAS  Article  Google Scholar 

  4. Bridge, D., Cunningham, C. W., DeSalle, R. & Buss, L. W. Class-level relationships in the phylum Cnidaria: molecular and morphological evidence. Mol. Biol. Evol. 12, 679–689 (1995)

    CAS  PubMed  Google Scholar 

  5. Peterson, K. J. et al. Estimating metazoan divergence times with a molecular clock. Proc. Natl Acad. Sci. USA 101, 6536–6541 (2004)

    ADS  CAS  Article  Google Scholar 

  6. Hobmayer, B. et al. WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra. Nature 407, 186–189 (2000)

    ADS  CAS  Article  Google Scholar 

  7. Holland, L. Z. Heads or tails? Amphioxus and the evolution of anterior-posterior patterning in deuterostomes. Dev. Biol. 241, 209–228 (2002)

    CAS  Article  Google Scholar 

  8. Conway Morris, S. The Cambrian “explosion”: slow-fuse or megatonnage? Proc. Natl Acad. Sci. USA 97, 4426–4429 (2000)

    ADS  CAS  Article  Google Scholar 

  9. Primus, A. & Freeman, G. The cnidarian and the canon: the role of Wnt/beta-catenin signaling in the evolution of metazoan embryos. Bioessays 26, 474–478 (2004)

    CAS  Article  Google Scholar 

  10. Marsal, M., Pineda, D. & Salo, E. Gtwnt-5, a member of the wnt family, expressed in a subpopulation of the nervous system of the planarian Girardia tigrina. Gene Expr. Patterns 3, 489–495 (2003)

    CAS  Article  Google Scholar 

  11. Nusse, R. An ancient cluster of Wnt paralogues. Trends Genet. 17, 443 (2001)

    CAS  Article  Google Scholar 

  12. King, N., Hittinger, C. T. & Carroll, S. B. Evolution of key cell signaling and adhesion protein families predates animal origins. Science 301, 361–363 (2003)

    ADS  CAS  Article  Google Scholar 

  13. Fritzenwanker, J. H., Saina, M. & Technau, U. Analysis of forkhead and snail expression reveals epithelialmesenchymal transitions during embryonic and larval development of Nematostella vectensis . Dev. Biol. 275, 389–402 (2004)

    CAS  Article  Google Scholar 

  14. Salvini-Plawen, L. On the origin and evolution of the lower Metazoa. Z. Zool. Syst. Evol. 16, 40–88 (1978)

    Article  Google Scholar 

  15. Finnerty, J. R., Pang, K., Burton, P., Paulson, D. & Martindale, M. Q. Origins of bilateral symmetry: Hox and dpp expression in a sea anemone. Science 304, 1335–1337 (2004)

    ADS  CAS  Article  Google Scholar 

  16. Angerer, L. M. & Angerer, R. C. Patterning the sea urchin embryo: gene regulatory networks, signaling pathways, and cellular interactions. Curr. Top. Dev. Biol. 53, 159–198 (2003)

    CAS  Article  Google Scholar 

  17. Le Gouar, M. et al. Expression of a SoxB and a Wnt2/13 gene during the development of the mollusc Patella vulgata . Dev. Genes Evol. 214, 250–256 (2004)

    Article  Google Scholar 

  18. Lengyel, J. A. & Iwaki, D. D. It takes guts: the Drosophila hindgut as a model system for organogenesis. Dev. Biol. 243, 1–19 (2002)

    CAS  Article  Google Scholar 

  19. Technau, U. & Scholz, C. B. Origin and evolution of endoderm and mesoderm. Int. J. Dev. Biol. 47, 531–539 (2003)

    PubMed  Google Scholar 

  20. Martindale, M. Q., Pang, K. & Finnerty, J. R. Investigating the origins of triploblasty: ‘mesodermal’ gene expression in a diploblastic animal, the sea anemone Nematostella vectensis (phylum, Cnidaria; class, Anthozoa). Development 131, 2463–2474 (2004)

    CAS  Article  Google Scholar 

  21. Davidson, B. & Levine, M. Evolutionary origins of the vertebrate heart: Specification of the cardiac lineage in Ciona intestinalis . Proc. Natl Acad. Sci. USA 100, 11469–11473 (2003)

    ADS  CAS  Article  Google Scholar 

  22. Christian, J. L., McMahon, J. A., McMahon, A. P. & Moon, R. T. Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. Development 111, 1045–1055 (1991)

    CAS  PubMed  Google Scholar 

  23. Hoppler, S. & Moon, R. T. BMP-2/-4 and Wnt-8 cooperatively pattern the Xenopus mesoderm. Mech. Dev. 71, 119–129 (1998)

    CAS  Article  Google Scholar 

  24. McMahon, A. P. & Bradley, A. The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell 62, 1073–1085 (1990)

    CAS  Article  Google Scholar 

  25. 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 

  26. Landesman, Y. & Sokol, S. Y. Xwnt-2b is a novel axis-inducing Xenopus Wnt, which is expressed in embryonic brain. Mech. Dev. 63, 199–209 (1997)

    CAS  Article  Google Scholar 

  27. Nakagawa, S., Takada, S., Takada, R. & Takeichi, M. Identification of the laminar-inducing factor: Wnt-signal from the anterior rim induces correct laminar formation of the neural retina in vitro . Dev. Biol. 260, 414–425 (2003)

    CAS  Article  Google Scholar 

  28. Holland, P. W. & Garcia-Fernandez, J. Hox genes and chordate evolution. Dev. Biol. 173, 382–395 (1996)

    CAS  Article  Google Scholar 

  29. Ng, M. & Yanofsky, M. F. Function and evolution of the plant MADS-box gene family. Nature Rev. Genet. 2, 186–195 (2001)

    CAS  Article  Google Scholar 

  30. Vinh, L. S. & von Haeseler, A. IQPNNI: Moving fast through tree space and stopping in time. Mol. Biol. Evol. 21, 1565–1571 (2004)

    CAS  Article  Google Scholar 

Download references


This work was supported by grants from NASA and the NSF to M.Q.M. and the German Science Foundation (DFG) to U.T., B.H. and T.W.H. Some computations were carried out on the JUMP supercomputer at the ZAM/NIC of the Research Center Jülich. We thank A. Busch and C. Niehrs for critically reading the manuscript.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Mark Q. Martindale or Thomas W. Holstein.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1

A ML tree of Wnt gene phylogeny reconstructed with TREE-PUZZLE using the JTT model with default settings. (PDF 206 kb)

Supplementary Figure S2

A ML tree of Wnt gene phylogeny reconstructed with the IQPNNI program assuming 8 G-distributed mutation rates with the JTT model of evolution. (PDF 212 kb)

Supplementary Figure S3

A 50% majority-rule consensus tree of Wnt gene phylogeny reconstructed from 1000 bootstrap samples with PAUP*. (PDF 204 kb)

Supplementary Figure S4

Asymmetrical Expression of the NvWntA gene in Nematostella vectensis embryos. (JPG 34 kb)

Supplementary Figure S5

Expression of NvWnt7 in Nematostella vectensis embryos. (JPG 33 kb)

Supplementary Figure S6

Expression of NvWnt5 in Nematostella vectensis embryos. (JPG 70 kb)

Supplementary Table 1

Accession numbers and list of Wnt sequences used in the phylogenetic reconstructions. (PDF 956 kb)

Supplementary Table 2

Alignment of Wnt sequences from Nematostella vectensis, and representative bilaterians used in the phylogenetic reconstructions. (PDF 1277 kb)

Supplementary Methods

Detailed description of phylogenetic methods used in this study. (DOC 26 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kusserow, A., Pang, K., Sturm, C. et al. Unexpected complexity of the Wnt gene family in a sea anemone. Nature 433, 156–160 (2005).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


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.


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