Dishevelled: in vivo roles of a multifunctional gene family during development.

Dishevelled proteins are highly conserved throughout evolution and participate in canonical and noncanonical Wnt pathways. In particular, Dvls participate in the planar cell polarity (PCP) pathway that is important for a variety of developmental processes. There are three Dvl genes in mammals. These three genes are highly conserved and broadly expressed throughout development and in the adult. Studies of mice with disruption of a single Dvl gene have revealed phenotypes that range from defective social behavior to developmental defects that include abnormal heart, skeletal, and cochlear morphogenesis, suggesting that each of the Dvl genes had unique functions. However, analysis of double or triple Dvl knock-outs revealed novel phenotypes or more severe phenotypes displayed by single knock-outs suggesting overlapping or redundant functions of these Dvl genes. Most if not all of the phenotypes displayed by the Dvl mutants appear to be the result of PCP pathway functions, not of the canonical Wnt pathway. This suggests that the PCP pathway is sensitive to reduction of Dvls, but only one Dvl allele of six may be required for Wnt pathway.