A SINGLE HOMEODOMAIN BINDING-SITE RESTRICTS SPATIAL EXPRESSION OF WNT-1 IN THE DEVELOPING BRAIN

In this study we investigate the molecular mechanisms that are respons ible for the restricted expression of Wnt-1 during embryogenesis. We r eport that a single homeodomain binding site, HBS1, within the Wnt-1 e nhancer contributes to appropriate spatial expression of Wnt-1 in the developing nervous system. This HBS1 site may be required for repressi ng Wnt-1 expression in the developing forebrain since specific mutatio ns of this site result in an extension of the rostral boundary of Wnt- 1/lacZ staining in transgenic embryos. We further demonstrate that a s ubset of homeodomain proteins expressed in the forebrain (i.e., D1x2, Emx2) interact specifically with HBS1. These findings suggest that the se (or related) homeodomain proteins may regulate expression of Wnt-1 during normal brain development by interacting with the HBS1 site in t he Wnt-1 enhancer.