Fig. 9. EMX2 is a direct repressor of Wnt1 in the developing telencephalon. (A) Model for normal regulation of Wnt1 in the embryonic forebrain. Previous work indicates that EMX2 directly binds HBS sequences located in the 3' enhancer region (Danielian and McMahon, 1996; Iler et al., 1995). We speculate that EMX2 represses Wnt1 expression via local effects on activating transcription factors that directly bind Wnt1 cis-acting regulatory sequences or via long-range effects. (B) In the absence of Emx2 function or intact HBS DNA-binding sequences, Wnt1 is ectopically expressed in the developing telencephalon (green arrow), causing abnormalities of marginal zone and subplate development in the superficial cerebral cortex. Our data do not rule out that interactions of other homeodomain factors (e.g. MSX1) with EMX2 at the HBS sequences may also be necessary for repression of Wnt1 expression in the forebrain.

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