Fig. 7. Wnt signaling and diencephalic patterning. A widespread Wnt signal induces the expression of Irx3 in the developing forebrain, which specifies a posterior, dT-committed fate. Irx3 expression allows the induction of Gbx2 by signals released from the zli, which might include Wnt3 and Wnt3a. Neural tissue that overlies the prechordal plate is exposed to Wnt antagonists, which results in the expression of Six3. In turn, Six3 allows the induction of Dlx2 in response to zli-derived signals and represses the expression of Irx3, Wnt3 and Gbx2. This model predicts that the zli will form at the interface between the domains of Six3 and Irx3 expression, above the transition between the notochord and the prechordal plate. Wnt3 is expressed throughout the prospective dT, just posterior to the zli (Fig. 1B) (Roelink and Nusse, 1991). The diencephalic phenotype of the Wnt3a-knockout mouse is unknown because it has a lethal gastrulation defect that prevents analysis of the role of Wnt3 in forebrain development (Lee et al., 1997; Liu et al., 1999). Because of their largely overlapping expression patterns and nearly identical protein sequences, it is likely that Wnt3 and Wnt3a have partially redundant functions in brain development, which would explain the relatively mild phenotype observed in Wnt3a^–/– mice. Given the expression patterns of Wnt3 and Wnt3a in the diencephalon, these molecules are good candidates for inductive signals that either confer or maintain posterior identity on prospective dT tissue.