title: The Wingless morphogen gradient is established by the cooperative action of Frizzled and Heparan Sulfate Proteoglycan receptors.
abstract: We have examined the respective contribution of Heparan Sulfate Proteoglycans (HSPGs) and Frizzled (Fz) proteins in the establishment of the Wingless (Wg) morphogen gradient. From the analysis of mutant clones of sulfateless/N-deacetylase-sulphotransferase in the wing imaginal disc, we find that lack of Heparan Sulfate (HS) causes a dramatic reduction of both extracellular and intracellular Wg in receiving cells. Our studies, together with others [Kirkpatrick, C.A., Dimitroff, B.D., Rawson, J.M., Selleck, S.B., 2004. Spatial regulation of Wingless morphogen distribution and signalling by Dally-like protein. Dev. Cell (in press)], reveals that the Glypican molecule Dally-like Protein (Dlp) is associated with both negative and positive roles in Wg short- and long-range signaling, respectively. In addition, analyses of the two Fz proteins indicate that the Fz and DFz2 receptors, in addition to transducing the signal, modulate the slope of the Wg gradient by regulating the amount of extracellular Wg. Taken together, our analysis illustrates how the coordinated activities of HSPGs and Fz/DFz2 shape the Wg morphogen gradient.
authors.affiliation: Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Gyeong-Hun
authors.initials: GH
authors.lastname: Baeg
authors.forename: Erica M
authors.initials: EM
authors.lastname: Selva
authors.forename: Robyn M
authors.initials: RM
authors.lastname: Goodman
authors.forename: Ramanuj
authors.initials: R
authors.lastname: Dasgupta
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
mesh_terms: D000818:Animals; D002999:Clone Cells; D004330:Drosophila / Q000196:embryology / Q000254:growth & development; D029721:Drosophila Proteins / Q000378:metabolism*; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D011509:Proteoglycans / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D014018:Tissue Distribution; D014921:Wings, Animal / Q000196:embryology / Q000254:growth & development; D051155:Wnt1 Protein
chemical_list: D029721:Drosophila Proteins; D051157:Frizzled Receptors; D019812:Heparan Sulfate Proteoglycans; D019476:Insect Proteins; D008565:Membrane Proteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D051155:Wnt1 Protein; C420997:dlp protein, Drosophila; C058784:fz protein, Drosophila; C074622:wg protein, Drosophila