Dact family molecules in Wnt signaling in mouse development.

摘要

The Wnt (Wingless-Integration) molecular signaling pathways are known to be integral in the embryonic patterning of multicellular animals, and are misregulated in multiple types of cancer. Wnt signaling includes multiple biochemical signaling pathways downstream of the Wnt family of secreted proteins and their receptors. Many, and possibly all, of these pathways converge on the intracellular protein Dishevelled, whose interactions appear essential in determining the cell-autonomous effects of the Wnt signal. Dact (Dapper, Antagonist of Beta Catenin Targeting) proteins were identified based on their binding to Dishevelled. There are three Dact encoding genes in mammals, and these show unique expression patterns in the development of the mouse. A mouse mutant lacking the Dact1 gene has been constructed. Despite expression of this gene in patterns suggesting roles in somitogenesis and neuronogenesis, Dact1 mutant mice are caudally truncated due to defective mesoderm formation in late gastrulation. Dact1 mutant mice show reduced Wnt/beta-catenin signaling. The Dact1 mutation and the mouse planar cell polarity mutant Loop-tail rescue one another's phenotypes, showing antagonism between Wnt/beta-catenin and planar cell polarity signaling pathways at the level of Dact1.