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Zebrafish Naked1 and Naked2 antagonize both canonical and non-canonical Wnt signaling.

Wnt signaling controls a wide range of developmental processes and its aberrant regulation can lead to disease. To better understand the regulation of this pathway, we identified zebrafish homologues of Naked Cuticle (Nkd), Nkd1 and Nkd2, which have previously been shown to inhibit canonical Wnt/beta-catenin signaling. Zebrafish nkd1 expression increases substantially after the mid-blastula transition in a pattern mirroring that of activated canonical Wnt/beta-catenin signaling, being expressed in both the ventrolateral blastoderm margin and also in the axial mesendoderm. In contrast, zebrafish nkd2 is maternally and ubiquitously expressed. Overexpression of Nkd1 or Nkd2a suppressed canonical Wnt/beta-catenin signaling at multiple stages of early zebrafish development and also exacerbated the cyclopia and axial mesendoderm convergence and extension (C&E) defect in the non-canonical Wnt/PCP mutant silberblick (slb/wnt11). Thus, Nkds are sufficient to antagonize both canonical and non-canonical Wnt signaling. Reducing Nkd function using antisense morpholino oligonucleotides resulted in increased expression of canonical Wnt/beta-catenin target genes. Finally, reducing Nkd1 function in slb mutants suppressed the axial mesendoderm C&E defect. These data indicate that zebrafish Nkd1 and Nkd2 function to limit both canonical and non-canonical Wnt signaling.

Pubmed ID: 17689523

Authors

  • Van Raay TJ
  • Coffey RJ
  • Solnica-Krezel L

Journal

Developmental biology

Publication Data

September 15, 2007

Associated Grants

  • Agency: PHS HHS, Id: P50 95103
  • Agency: NCI NIH HHS, Id: P50 CA095103
  • Agency: NCI NIH HHS, Id: P50 CA095103-04
  • Agency: NCI NIH HHS, Id: R01 CA46413
  • Agency: NIGMS NIH HHS, Id: R01 GM055101
  • Agency: NIGMS NIH HHS, Id: R01 GM055101-09
  • Agency: NIGMS NIH HHS, Id: R01 GM055101-10
  • Agency: NIGMS NIH HHS, Id: R01 GM55101
  • Agency: PHS HHS, Id: U01 084239
  • Agency: NCI NIH HHS, Id: U01 CA084239
  • Agency: NCI NIH HHS, Id: U01 CA084239-10

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Blastula
  • Body Patterning
  • Carrier Proteins
  • Molecular Sequence Data
  • Mutation
  • Signal Transduction
  • Wnt Proteins
  • Zebrafish
  • Zebrafish Proteins
  • beta Catenin