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Vol. 17, No. 3, pp. 368-379, February 1, 2003
1 Department of Genetics, St. Jude Children's Research
Hospital, Memphis, Tennessee 38105-2794, USA; 2 Department 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;
4 Department of Morphological Sciences, Faculty of Medicine,
University of Murcia, E-30100 Murcia, Spain
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.
[Keywords: Six3; forebrain; mouse; homeobox; Wnt; zebrafish]
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