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Repressor activity of Headless/Tcf3 is essential for vertebrate head formation

Nature volume 407, pages 913–916 (2000)Cite this article

Abstract

The vertebrate organizer can induce a complete body axis when transplanted to the ventral side of a host embryo1 by virtue of its distinct head and trunk inducing properties. Wingless/Wnt antagonists secreted by the organizer have been identified as head inducers2,3,4. Their ectopic expression can promote head formation, whereas ectopic activation of Wnt signalling during early gastrulation blocks head formation5,6,7. These observations suggest that the ability of head inducers to inhibit Wnt signalling during formation of anterior structures is what distinguishes them from trunk inducers that permit the operation of posteriorizing Wnt signals8. Here we describe the zebrafish headless (hdl) mutant and show that its severe head defects are due to a mutation in T-cell factor-3 (Tcf3), a member of the Tcf/Lef family9,10. Loss of Tcf3 function in the hdl mutant reveals that hdl represses Wnt target genes. We provide genetic evidence that a component of the Wnt signalling pathway is essential in vertebrate head formation and patterning.

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Figure 1: Morphological analysis.
Figure 2: Gene expression analyses.
Figure 3: Mapping of the hdl/tcf3 gene.
Figure 4: Rescue by Tcf3 expression.

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Acknowledgements

We thank R. T. Moon, R. Dorsky, T. Hirano, M. Hibi, A. Kawahara, L. Kodjabachian, D. Turner, M. Halpern and M. Kobayashi for constructs; M. Kacergis and G. Palardy for technical assistance; R. Subramanian and members of the Dawid lab for comments on the manuscript. The mutagenesis screen was performed at CVRC/MGH/Harvard Medical School. This work was supported by the NIH.

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Authors and Affiliations

  1. Laboratory of Molecular Genetics, NICHD,

    Cheol-Hee Kim, Motoyuki Itoh, Di Jiang & Ajay B. Chitnis

  2. Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, 20892, Maryland, USA

    Takaya Oda & Settara C. Chandrasekharappa

  3. Department of Cell Biology, Harvard Medical School, Boston, 02115 , Massachusetts, USA

    Kristin Bruk Artinger

  4. University of Freiburg, Institute for Zoology, Hauptstrasse 1, Freiburg, D-79104, Germany

    Wolfgang Driever

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  1. Cheol-Hee Kim
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Correspondence to Ajay B. Chitnis.

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Kim, CH., Oda, T., Itoh, M. et al. Repressor activity of Headless/Tcf3 is essential for vertebrate head formation. Nature 407, 913–916 (2000). https://doi.org/10.1038/35038097

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