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

Genes Dev. 2003 Feb 1;17(3):368-79. doi: 10.1101/gad.1059403.


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 of Wnt1 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ectoderm / physiology
  • Eye Proteins
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Prosencephalon / abnormalities
  • Prosencephalon / embryology*
  • Proto-Oncogene Proteins / metabolism*
  • Signal Transduction / physiology*
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish / genetics
  • Zebrafish Proteins*


  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Sine oculis homeobox homolog 3 protein
  • Wnt Proteins
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Zebrafish Proteins
  • wnt8b protein, zebrafish