title: The endocytic pathway and formation of the Wingless morphogen gradient.
abstract: Controlling the spread of morphogens is crucial for pattern formation during development. In the Drosophila wing disc, Wingless secreted at the dorsal-ventral compartment boundary forms a concentration gradient in receiving tissue, where it activates short- and long-range target genes. The glypican Dally-like promotes Wingless spreading by unknown mechanisms, while Dynamin-dependent endocytosis is thought to restrict Wingless spread. We have utilized short-term expression of dominant negative Rab proteins to examine the polarity of endocytic trafficking of Wingless and its receptors and to determine the relative contributions of endocytosis, degradation and recycling to the establishment of the Wingless gradient. Our results show that Wingless is internalized via two spatially distinct routes: one on the apical, and one on the basal, side of the disc. Both restrict the spread of Wingless, with little contribution from subsequent degradation or recycling. As previously shown for Frizzled receptors, depleting Arrow does not prevent Wingless from entering endosomes. We find that both Frizzled and Arrow are internalized mainly from the apical membrane. Thus, the basal Wingless internalization route must be independent of these proteins. We find that Dally-like is not required for Wingless spread when endocytosis is blocked, and propose that Dally-like promotes the spread of Wingless by directing it to lateral membranes, where its endocytosis is less efficient. Thus, subcellular localization of Wingless along the apical-basal axis of receiving cells may be instrumental in shaping the Wingless gradient.
authors.affiliation: Max-Planck Institute for Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Marois
authors.forename: Ali
authors.initials: A
authors.lastname: Mahmoud
authors.forename: Suzanne
authors.initials: S
authors.lastname: Eaton
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D051157:Frizzled Receptors; D017344:Genes, Insect; D008954:Models, Biological; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014921:Wings, Animal / Q000254:growth & development / Q000378:metabolism; D051155:Wnt1 Protein; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D051157:Frizzled Receptors; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D051155:Wnt1 Protein; C474373:arr protein, Drosophila; C420997:dlp protein, Drosophila; C101703:fz2 protein, Drosophila; D000090802:rab7 GTP-Binding Proteins; C074622:wg protein, Drosophila; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins