Linking Frizzled and Wnt signaling in Drosophila development.
Drosophila Frizzled-2 (Dfz2) has been identified as a putative fly Wingless (Wg) receptor. Although Dfz2 shows significant homology with Fz, a protein that operates in the mechanisms that establish planar polarity in Drosophila epithelia, any clear evidence for an involvement by Fz in a Wnt signaling pathway has hitherto been absent. Here we describe the planar polarity phenotypes of loss-of-function and overexpression of Fz in the developing Drosophila eye and find it almost identical to the loss-of-function or overexpression of Dishevelled (Dsh - a protein operating in Wnt second messenger systems). In addition, we show that overexpression of Shaggy (Sgg - another component of the Wnt pathway) in the eye also causes a phenotype similar to Fz and Dsh. To test further the link between planar polarity and Wnt signaling we misexpressed Wg in the developing eye and found it had a potent polarizing effect in the retinal epithelium. Since the overexpression of Fz in the developing eye gave a phenotype consistent with activating the Wnt pathway, we tested overexpression of Fz in the developing embryonic ectoderm and found that it phenocopied overexpression of Wg. To check that Fz was indeed able to activate a Wnt pathway we overexpressed it in Drosophila tissue culture cells and observed the characteristic phosphorylation of Dsh that occurs in response to Wnt signaling. Taken together our results significantly strengthen the case for Fz acting in a Wnt signaling pathway in Drosophila.
Tomlinson
A
A
Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Strapps
W R
WR
Heemskerk
J
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002460:Cell Line; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D005123:Eye / Q000196:embryology / Q000378:metabolism; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D038362:Glycogen Synthase Kinase 3; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D015398:Signal Transduction; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D019476:Insect Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; C000606588:dsh protein, Drosophila; C058784:fz protein, Drosophila; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila; D017346:Protein Serine-Threonine Kinases; C080335:Sgg protein, Drosophila; D038362:Glycogen Synthase Kinase 3