An ancient role for nuclear β-catenin in the evolution of axial polarity and germ layer segregation


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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Figure 1: Lithium chloride treatment of N. vectensis embryos results in the hyperproliferation of entoderm at gastrulation.
Figure 2: The temporal and spatial dynamics of β-catenin–GFP protein in live N. vectensis embryos. mRNA coding for the fusion protein (green) was co-injected with rhodamine dextran (red) into zygotes.
Figure 3: Immunohistochemical localization of endogenous N. vectensis β-catenin.
Figure 4: Blocking the nuclear function of β-catenin inhibits entoderm formation in N. vectensis.


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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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Correspondence to Athula H. Wikramanayake or Mark Q. Martindale.

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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).

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