THE MOUSE FUSED LOCUS ENCODES AXIN, AN INHIBITOR OF THE WNT SIGNALINGPATHWAY THAT REGULATES EMBRYONIC AXIS FORMATION

Mutations at the mouse Fused locus have pleiotropic developmental effe cts, including the formation of axial duplications in homozygous embry os. The product of the Fused locus, Axin, displays similarities to RGS (Regulators of G-Protein Signaling) and Dishevelled proteins. Mutant Fused alleles that cause axial duplications disrupt the major mRNA, su ggesting that Axin negatively regulates the response to an axis-induci ng signal. Injection of Axin mRNA into Xenopus embryos inhibits dorsal axis formation by interfering with signaling through the Wnt pathway. Furthermore, ventral injection of an Axin mRNA lacking the RGS domain induces an ectopic axis, apparently through a dominant-negative mecha nism. Thus, Axin is a novel inhibitor of Wnt signaling and regulates a n early step in embryonic axis formation in mammals and amphibians.