A mutation in the Gsk3–binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon

  1. Carl-Philipp Heisenberg1,5,
  2. Corinne Houart1,6,
  3. Masaya Take-uchi1,6,
  4. Gerd-Jörg Rauch2,
  5. Neville Young3,
  6. Pedro Coutinho4,
  7. Ichiro Masai1,
  8. Luca Caneparo1,
  9. Miguel L. Concha1,
  10. Robert Geisler2,
  11. Trevor C. Dale3,
  12. Stephen W. Wilson1,7, and
  13. Derek L. Stemple4
  1. 1Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK; 2Abteilung Genetik, Max-Planck-Institut für Entwicklungsbiologie, 72076 Tübingen, Germany; 3Developmental Biology, Section of Cell Biology and Experimental Pathology, Toby Robins Breakthrough Breast Cancer Research Center, Institute of Cancer Research, London SW3 6JB, UK; 4Division of Developmental Biology, National Institute of Medical Research, Mill Hill, London NW7 1AA, UK

Abstract

Zebrafish embryos homozygous for the masterblind(mbl) mutation exhibit a striking phenotype in which the eyes and telencephalon are reduced or absent and diencephalic fates expand to the front of the brain. Here we show that mbl −/−embryos carry an amino-acid change at a conserved site in the Wnt pathway scaffolding protein, Axin1. The amino-acid substitution present in the mbl allele abolishes the binding of Axin to Gsk3 and affects Tcf-dependent transcription. Therefore, Gsk3 activity may be decreased in mbl −/− embryos and in support of this possibility, overexpression of either wild-type Axin1 or Gsk3β can restore eye and telencephalic fates to mbl −/−embryos. Our data reveal a crucial role for Axin1-dependent inhibition of the Wnt pathway in the early regional subdivision of the anterior neural plate into telencephalic, diencephalic, and eye-forming territories.

Keywords

Footnotes

  • ↵5 Present address: Max-Planck-Institute for Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany.

  • ↵6 These authors contributed equally to this work.

  • ↵7 Corresponding author.

  • E-MAIL s.Wilson{at}ucl.ac.uk; FAX 207-679-7349.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.194301.

    • Received November 24, 2000.
    • Accepted March 28, 2001.
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  1. doi: 10.1101/gad.194301 Genes & Dev. 15: 1427-1434 Cold Spring Harbor Laboratory Press

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