Dishevelled: at the crossroads of divergent intracellular signaling pathways

During the development of multicellular organisms the formation of complex patterns relies on specific cell-cell signaling events. For tissues to beco me spatially organized and cells to become committed to specialized fates i t is absolutely crucial for proper development that the underlying signalin g systems receive and route information correctly. Recently, a wealth of ge netic and biochemical experimental data has been collected about prevalent evolutionary conserved signaling families, such as the Wnts, Dpp/BMPs, and Hedgehogs, in flies, worms, and vertebrates. Paradoxically, members of a pa rticular signaling family often have receptors with similar biochemical bin ding properties, though they activate different intracellular pathways in v ivo and can be phenotypically distinguished. How are their specific biologi cal responses then generated? With respect to signaling specificity in Wnt pathways, Dishevelled is an intriguing protein; in Drosophila melanogaster it is required in two distinct signaling pathways, that share Frizzled rece ptors of similar structure, but have distinct intracellular signaling route s. Recent results suggest that Dishevelled is a multifunctional protein at the crossroads of divergent Wnt/Fz pathways. Dishevelled appears to be a ke y factor in Wnt signaling to 'read' signals coming from the plasma membrane and route them into the correct intracellular pathways. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.