Silencing of Smed-betacatenin1 generates radial-like hypercephalized planarians.
Little is known about the molecular mechanisms responsible for axis establishment during non-embryonic processes such as regeneration and homeostasis. To address this issue, we set out to analyze the role of the canonical Wnt pathway in planarians, flatworms renowned for their extraordinary morphological plasticity. Canonical Wnt signalling is an evolutionarily conserved mechanism to confer polarity during embryonic development, specifying the anteroposterior (AP) axis in most bilaterians and the dorsoventral (DV) axis in early vertebrate embryos. beta-Catenin is a key element in this pathway, although it is a bifunctional protein that is also involved in cell-cell adhesion. Here, we report the characterization of two beta-catenin homologs from Schmidtea mediterranea (Smed-betacatenin1/2). Loss of function of Smed-betacatenin1, but not Smed-betacatenin2, in both regenerating and intact planarians, generates radial-like hypercephalized planarians in which the AP axis disappears but the DV axis remains unaffected, representing a unique example of a striking body symmetry transformation. The radial-like hypercephalized phenotype demonstrates the requirement for Smed-betacatenin1 in AP axis re-establishment and maintenance, and supports a conserved role for canonical Wnt signalling in AP axis specification, whereas the role of beta-catenin in DV axis establishment would be a vertebrate innovation. When considered alongside the protein domains present in each S. mediterranea beta-catenin and the results of functional assays in Xenopus embryos demonstrating nuclear accumulation and axis induction with Smed-betacatenin1, but not Smed-betacatenin2, these data suggest that S. mediterranea beta-catenins could be functionally specialized and that only Smed-betacatenin1 is involved in Wnt signalling.
PubMed ID: 18287199
Article link: Development.
Genes referenced: cat2 cdh3 cdx4 ctnnb1 egr2 gsk3b otx2
Antibodies referenced: Somite Ab1
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|Fig. 4. mRNA injection of Smed-βcatenin1 but not Smed-βcatenin2 induces a secondary axis in Xenopus embryos. (A,B) Xenopus embryos injected with Smed-βcatenin1 (A) or Smed-βcat2 RNA (B), showing Otx2 (forebrain, red arrow), Krox20 (rhombomeres 3 and 5, green arrows) and Cad3 (spinal cord, white arrows) expression, along with muscle staining with the antibody 12/101 (brown signal). A schematic representation of the structure of each β-catenin is shown under the corresponding image. GSK3-binding domain and adhesion domains are shown with red and blue boxes, respectively. (C-H) Neurula (C-F) and tailbud (G,H) stage embryos injected with GFP-tagged constructs for both Schmidtea mediterranea β-catenins. (I,J) Smed-βcatenin1 but not Smed-βcatenin2 is found preferentially in the cell nucleus. (K) Quantification of the secondary axis obtained after each Smed-βcatenin injection (Xenopus β-catenin was used as a control).|