Mutation and Analysis of Dan , the Founding Member of the Dan Family of Transforming Growth Factor β Antagonists

Abstract

ABSTRACT The Dan family of transforming growth factor β antagonists is a large, evolutionarily conserved family of proteins. Little is known about either the specificity of these antagonists or the biological roles of these proteins. We have characterized Dan , the founding member of this family, with regard to both its biochemical specificity and its biological roles. Although DAN is not an efficient antagonist of BMP-2/4 class signals, we found that DAN 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. Intriguingly, in developing neurons, Dan mRNA was localized to axons, suggesting a potential role for the DAN protein in axonal outgrowth or guidance. Mice lacking Dan activity were generated by gene targeting and displayed subtle, background-dependent defects.