Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development

  1. Oleg V. Lagutin1,
  2. Changqi C. Zhu1,
  3. Daisuke Kobayashi2,
  4. Jacek Topczewski3,
  5. Kenji Shimamura2,
  6. Luis Puelles4,
  7. Helen R.C. Russell1,
  8. Peter J. McKinnon1,
  9. Lilianna Solnica-Krezel3, and
  10. Guillermo Oliver1,5
  1. 1Department of Genetics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA; 2Department of Neurobiology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan; 3 Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37232, USA; 4Department of Morphological Sciences, Faculty of Medicine, University of Murcia, E-30100 Murcia, Spain

Abstract

In vertebrate embryos, formation of anterior neural structures requires suppression of Wnt signals emanating from the paraxial mesoderm and midbrain territory. In Six3 −/− mice, the prosencephalon was severely truncated, and the expression ofWnt1 was rostrally expanded, a finding that indicates that the mutant head was posteriorized. Ectopic expression of Six3 in chick and fish embryos, together with the use of in vivo and in vitro DNA-binding assays, allowed us to determine that Six3 is a direct negative regulator of Wnt1 expression. These results, together with those of phenotypic rescue of headless/tcf3 zebrafish mutants by mouse Six3, demonstrate that regionalization of the vertebrate forebrain involves repression of Wnt1 expression by Six3 within the anterior neuroectoderm. Furthermore, these results support the hypothesis that a Wnt signal gradient specifies posterior fates in the anterior neural plate.

Keywords

Footnotes

  • 5 Corresponding author.

  • E-MAIL guillermo.oliver{at}stjude.org; FAX (901) 526-2907.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1059403.

    • Received November 15, 2002.
    • Accepted December 9, 2002.
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