Mutation and analysis of Dan, the founding member of the Dan family of transforming growth factor beta antagonists

The Dan family of transforming growth factor beta antagonists is a large, e volutionarily conserved family of proteins. Little is known about either th e specificity of these antagonists or the biological roles of these protein s. We have characterized Dan, the founding member of this family, with rega rd to both its biochemical specificity and its biological roles. Although D AN is not an efficient antagonist of BMP-2/4 class signals, we found that D AN was able to interact with GDF-5 in a frog embryo assay, suggesting that DAN may regulate signaling by the GDF-5/6/7 class of BMPs in vivo. Intrigui ngly, in developing neurons, Dan mRNA was localized to axons, suggesting a potential role for the DAN protein in axonal outgrowth or guidance. Mice la cking Dan activity were generated by gene targeting and displayed subtle, b ackground-dependent defects.