Abstract
The human oncogene β-catenin is a bifunctional protein with critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway1,2,3. Wnt/β-catenin signalling has been implicated in developmental processes as diverse as elaboration of embryonic polarity2,3,4,5,6, formation of germ layers4,5,6,7,8, neural patterning, spindle orientation and gap junction communication2, but the ancestral function of β-catenin remains unclear. In many animal embryos, activation of β-catenin signalling occurs in blastomeres that mark the site of gastrulation and endomesoderm formation5,6,7,8,9,10, raising the possibility that asymmetric activation of β-catenin signalling specified embryonic polarity and segregated germ layers in the common ancestor of bilaterally symmetrical animals. To test whether nuclear translocation of β-catenin is involved in axial identity and/or germ layer formation in ‘pre-bilaterians’, we examined the in vivo distribution, stability and function of β-catenin protein in embryos of the sea anemone Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis β-catenin is differentially stabilized along the oral–aboral axis, translocated into nuclei in cells at the site of gastrulation and used to specify entoderm, indicating an evolutionarily ancient role for this protein in early pattern formation.
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References
Miller, J. R. & Moon, R. T. Signal transduction through beta-catenin and specification of cell fate during embryogenesis. Genes Dev. 10, 2527–2539 (1996)
Huelsken, J. & Birchmeier, W. New aspects of Wnt signalling pathways in higher vertebrates. Curr. Opin. Genet. Dev. 11, 547–553 (2001)
Polakis, P. Wnt signalling and cancer. Genes Dev. 14, 1837–1851 (2000)
Wikramanayake, A. H., Huang, L. & Klein, W. H. beta-catenin is essential for patterning the maternally specified animal-vegetal axis in the sea urchin embryo. Proc. Natl Acad. Sci. USA 95, 9343–9348 (1998)
Logan, C. Y., Miller, J. R., Ferkowicz, M. J. & McClay, D. R. Nuclear beta-catenin is required to specify vegetal cell fates in the sea urchin embryo. Development 126, 345–357 (1999)
Imai, K., Takada, N., Satoh, N. & Satou, Y. Beta-catenin mediates the specification of endoderm cells in ascidian embryos. Development 127, 3009–3020 (2000)
Thorpe, C. H., Schlesinger, A., Carter, J. C. & Bowerman, B. Wnt signalling polarizes an early C. elegans blastomere to distinguish endoderm from mesoderm. Cell 90, 695–705 (1997)
Rocheleau, C. E. et al. Wnt signalling and an APC related gene specify endoderm in early C. elegans embryos. Cell 90, 707–716 (1997)
Schneider, S., Steinbeisser, H., Warga, R. M. & Hausen, P. Beta-catenin translocation into nuclei demarcates the dorsalizing centres in frog and fish embryos. Mech. Dev. 57, 191–198 (1996)
Miyawaki, K. et al. Nuclear localization of beta-catenin in vegetal pole cells during early embryogenesis of the starfish Asterina pectinifera. Dev. Growth Differ. 45, 121–128 (2003)
Medina, M., Collins, A. G., Silberman, J. D. & Sogin, M. L. Evaluating hypotheses of basal animal phylogeny using complete sequences of large and small subunit rRNA. Proc. Natl Acad. Sci. USA 98, 9707–9712 (2001)
Collins, A. G. Evaluating multiple alternative hypothesis for the origin of Bilateria: An analysis of 18S rRNA molecular evidence. Proc. Natl Acad. Sci. USA 95, 15458–15463 (1998)
Hand, C. & Uhlinger, K. R. The culture, sexual and asexual reproduction, and growth of the sea anemone Nematostella vectensis. Biol. Bull. 182, 169–176 (1992)
Goldstein, B. & Freeman, G. Axis specification in animal development. Bioessays 19, 105–116 (1997)
Knoll, A. & Carroll, S. Early animal evolution: emerging views from comparative biology and geology. Science 284, 2129–2137 (1999)
Hobmayer, B. et al. WNT signalling molecules act in axis formation in the diploblastic metazoan Hydra. Nature 407, 186–189 (2000)
Klein, P. S. & Melton, D. A. A molecular mechanism for the effect of lithium on development. Proc. Natl Acad. Sci. USA 93, 8455–8459 (1996)
Kao, K. R. & Elinson, R. P. The legacy of lithium effects on development. Biol. Cell 90, 585–590 (1998)
Schneider, S. Q., Finnerty, J. R. & Martindale, M. Q. Protein evolution: structure-function relationships of the oncogene beta-catenin in the evolution of multicellular animals. J. Exp. Zool. B 295, 25–44 (2003)
Miller, J. R. & Moon, R. T. Analysis of the signalling activities of localization mutants of beta-catenin during axis specification in Xenopus. J. Cell Biol. 139, 229–243 (1997)
Weitzel, H. E. & Ettensohn, C. A. beta-catenin is differentially degraded along the animal-vegetal axis of early sea urchin embryos in a GSK-3b-dependent manner. Dev. Biol. 247, 479a (2002)
Yost, C. et al. The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3. Genes Dev. 10, 1443–1454 (1996)
Ding, Y. & Dale, T. Wnt signal transduction: kinase cogs in a nano-machine? Trends Biochem. Sci. 27, 327–329 (2002)
Heasman, J. et al. Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. Cell 79, 791–803 (1994)
Montross, W. T., Ji, H. & McCrea, P. D. A beta-catenin/engrailed chimera selectively suppresses Wnt signalling. J. Cell Sci. 113, 1759–1770 (2000)
Freeman, G. & Miller, R. L. Hydrozoan eggs can only be fertilized at the site of polar body formation. Dev. Biol. 94, 142–152 (1982)
Larabell, C. A. et al. Establishment of the dorso-ventral axis in Xenopus embryos is presaged by early asymmetries in beta-catenin that are modulated by the Wnt signalling pathway. J. Cell Biol. 136, 1123–1136 (1997)
Mao, C.-A. et al. Altering cell fates in sea urchin embryos by overexpressing SpOtx, an orthodenticle-related protein. Development 122, 1489–1498 (1996)
Klymkowsky, M. W. & Hanken, J. Whole-mount staining of Xenopus and other vertebrates. Methods Cell Biol. 36, 419–441 (1991)
McCrea, P. D., Brieher, W. M. & Gumbiner, B. M. Induction of a secondary body axis in Xenopus by antibodies to beta-catenin. J. Cell Biol. 123, 477–484 (1993)
Acknowledgements
We thank Y. Marikawa, B. Klein and members of our laboratories for critical reading of the manuscript and for suggestions and P. McCrea for the gift of affinity-purified β-catenin antibody. This work was supported by grants from the NSF and the Hawaii Community Foundation to A.H.W. and by grants from the NSF and NASA to M.Q.M.
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Wikramanayake, A., Hong, M., Lee, P. et al. An ancient role for nuclear β-catenin in the evolution of axial polarity and germ layer segregation. Nature 426, 446–450 (2003). https://doi.org/10.1038/nature02113
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DOI: https://doi.org/10.1038/nature02113
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