title: Drosophila glypicans Dally and Dally-like shape the extracellular Wingless morphogen gradient in the wing disc.
abstract: Drosophila Wingless (Wg) is the founding member of the Wnt family of secreted proteins. During the wing development, Wg acts as a morphogen whose concentration gradient provides positional cues for wing patterning. The molecular mechanism(s) of Wg gradient formation is not fully understood. Here, we systematically analyzed the roles of glypicans Dally and Dally-like protein (Dlp), the Wg receptors Frizzled (Fz) and Fz2, and the Wg co-receptor Arrow (Arr) in Wg gradient formation in the wing disc. We demonstrate that both Dally and Dlp are essential and have different roles in Wg gradient formation. The specificities of Dally and Dlp in Wg gradient formation are at least partially achieved by their distinct expression patterns. To our surprise, although Fz2 was suggested to play an essential role in Wg gradient formation by ectopic expression studies, removal of Fz2 activity does not alter the extracellular Wg gradient. Interestingly, removal of both Fz and Fz2, or Arr causes enhanced extracellular Wg levels, which is mainly resulted from upregulated Dlp levels. We further show that Notum, a negative regulator of Wg signaling, downregulates Wg signaling mainly by modifying Dally. Last, we demonstrate that Wg movement is impeded by cells mutant for both dally and dlp. Together, these new findings suggest that the Wg morphogen gradient in the wing disc is mainly controlled by combined actions of Dally and Dlp. We propose that Wg establishes its concentration gradient by a restricted diffusion mechanism involving Dally and Dlp in the wing disc.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Han
authors.forename: Dong
authors.initials: D
authors.lastname: Yan
authors.forename: Tatyana Y
authors.initials: TY
authors.lastname: Belenkaya
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology; D051157:Frizzled Receptors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D011509:Proteoglycans / 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 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014921:Wings, Animal / Q000196:embryology / Q000378:metabolism*; D051155:Wnt1 Protein
chemical_list: D029721:Drosophila Proteins; D051157:Frizzled Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C456459:Notum protein, Drosophila; 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; C098128:dally protein, Drosophila; C420997:dlp protein, Drosophila; C058784:fz protein, Drosophila; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila