XB-ART-12245Mech Dev May 1, 1999; 83 (1-2): 27-37.
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 become spatially organized and cells to become committed to specialized fates it is absolutely crucial for proper development that the underlying signaling systems receive and route information correctly. Recently, a wealth of genetic 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 particular signaling family often have receptors with similar biochemical binding properties, though they activate different intracellular pathways in vivo and can be phenotypically distinguished. How are their specific biological 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 receptors of similar structure, but have distinct intracellular signaling routes. Recent results suggest that Dishevelled is a multifunctional protein at the crossroads of divergent Wnt/Fz pathways. Dishevelled appears to be a key factor in Wnt signaling to read'' signals coming from the plasma membrane and route them into the correct intracellular pathways.
PubMed ID: 10507837
Genes referenced: ctnnb1 dvl1 dvl2 fzd1 gsk3b tcf7 wnt1
Article Images: [+] show captions
|Fig. 1. The roles of dishevelled in Drosophila and Xenopus development. (A) dsh mutant phenotype during embryogenesis reveals defects in the establishment of segment borders (segment polarity class) and is very similar to wg mutants. A wild-type embryo is shown for comparison. The left panel shows the genetic pathway for wg signaling in this process. (B) The planar polarity phenotypes of the dsh1 allele. Left panels show the ommatidial arrangement in a dorsal area of the eye (wild type on top and dsh1 mutant below), with schematic presentation on the side (black arrow: correct alignment, red arrow: misrotated ommatidium, green arrow: wrong or no chiral form; arrows point towards the dorso-ventral midline of symmetry, the equator). Middle panels show the planar polarity wing phenotype; and right panel shows the genetic pathway required for the interpretation of the planar polarity signal. (C) The role of Dsh in Xenopus axis induction. Overexpression assays of Xenopus components of the Wnt signaling pathway causes axis bifurcation; compare WT with the injected Xdsh (OEXdsh) embryos. The Wnt pathway implicated in axis generation in Xenopus is similar to Wg signaling in Drosophila.|