A mutation in the Gsk3–binding domain of zebrafish Masterblind/Axin1 leads to a fate transformation of telencephalon and eyes to diencephalon
- Carl-Philipp Heisenberg1,5,
- Corinne Houart1,6,
- Masaya Take-uchi1,6,
- Gerd-Jörg Rauch2,
- Neville Young3,
- Pedro Coutinho4,
- Ichiro Masai1,
- Luca Caneparo1,
- Miguel L. Concha1,
- Robert Geisler2,
- Trevor C. Dale3,
- Stephen W. Wilson1,7, and
- Derek L. Stemple4
- 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.
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Footnotes
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↵5 Present address: Max-Planck-Institute for Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany.
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↵6 These authors contributed equally to this work.
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↵7 Corresponding author.
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E-MAIL s.Wilson{at}ucl.ac.uk; FAX 207-679-7349.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.194301.
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- Received November 24, 2000.
- Accepted March 28, 2001.
- Cold Spring Harbor Laboratory Press