XB-ART-41700Curr Biol. July 27, 2010; 20 (14): 1263-8.
Wnt/Frizzled signaling requires dPRR, the Drosophila homolog of the prorenin receptor.
Wnt/Wg signaling pathways are of key importance during development and disease. Canonical and noncanonical Wnt/Frizzled (Fz) pathways share a limited number of signaling components that are part of the membrane proximal signaling complex. In Drosophila, Fz and Dishevelled (Dsh) are the only two components known to be involved in both Wnt/beta-catenin and planar cell polarity (PCP) signaling. PCP signaling is required for the planar polarization of epithelial cells, which occurs, for instance, during hair orientation and gastrulation in vertebrates. Both pathways have been studied intensively in the past years. However, it still remains unresolved whether additional components are required at the receptor complex. Here we identify the Drosophila homolog of the mammalian prorenin receptor (dPRR) as a conserved modulator of canonical Wnt/beta-cat and Fz/PCP signaling. We show that dPRR depletion affects Wg target genes in cultured cells and in vivo. PRR is required for epithelial planar polarity in Drosophila and for convergent extension movements in Xenopus gastrulae. Furthermore, dPRR binds to Fz and Fz2 receptors. In summary, our data suggest that dPRR has an evolutionarily conserved role at the receptor level for activation of canonical and noncanonical Wnt/Fz signaling pathways.
PubMed ID: 20579883
Article link: Curr Biol.
Genes referenced: atf2 atp6ap2 cat.2 csnk1a1 dvl2 fzd2 nectin1 not
Morpholinos referenced: atp6ap2 MO1
Article Images: [+] show captions
|Figure 3. PRR Is Required for Planar Cell Polarity (A) Dorsal view of adult thoraces of the indicated genotypes. dsRNA hairpins were expressed under the control of apGal4 at 25ﰉC. RNAi of dPRR causes planar cell polarity-like phenotypes (B) that can be rescued by overexpression of hPRR (D). (E and F) Phalloidin staining of pupal wings of the indicated genotypes aged for w32 hr after pupal formation (APF), distal side to the left. Line indicates the approximate expression domain of ptcGal4. Note the affected ptc expression domain in dPRR RNAi animals. (G) Phalloidin staining of a pupal wing of the genotype ptcGal4/UAS-dPRR RNAi1 at 40 hr APF. (H) Adult wing of the genotype ptcGal4/UAS-dPRR RNAi1 at 25dC, anterior to the left. (I) Loss of PRR function causes gastrulation defects in Xenopus embryos. Top: four-cell stage embryos were microinjected equatorially into two dorsal blastomeres with PRR morpholinos (Mo). Note the stunted axis in embryos injected with PRR Mo (75%, n = 32), but not control Mo (0%, n = 30), embryos. Middle: in situ hybridization for Xnot at gastrula stage (stage 12). Bottom: PRR Mo inhibits elongation of activin-treated animal caps. (J) ATF2-luciferase reporter assay in Xenopus embryos. Four-cell stage embryos were injected equatorially with ATF2-Luc reporter plasmid, the indicated antisense morpholinos, and mRNAs. Luciferase reporter assays were carried out from whole embryos harvested at gastrula stage (stage 12). Data are shown as mean 6 standard deviation.|