During the development of vertebrate forebrain the formation of anterior neural structures requires suppression of Wnt signals originating from the paraxial mesoderm and midbrain territory. However, the exact signaling mechanisms that control forebrain patterning have been unclear. In the February 1 Genes & Development, Oleg V. Lagutin and colleagues at the St. Jude Children's Research Hospital, Memphis, Tennessee, USA, show that Six3 repression of Wnt signaling in the anterior neuroectoderm is essential for vertebrate forebrain development (Genes & Development, 17: 368-379, February 1, 2003).

Lagutin et al. inactivated the murine Six3 locus and observed that the prosencephalon was severely truncated and expression of Wnt1 was rostrally expanded, indicationg that the mutant head was posteriorized. In addition, ectopic expression of Six3 in chick and fish embryos showed that Six3 was a direct negative regulator of Wnt1 expression.

"Taken together, these results not only identified Six3 as a key...

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