title: The heparan sulfate proteoglycans Dally-like and Syndecan have distinct functions in axon guidance and visual-system assembly in Drosophila.
abstract: Heparan sulfate proteoglycans (HSPGs), a class of glycosaminoglycan-modified proteins, control diverse patterning events via their regulation of growth-factor signaling and morphogen distribution. In C. elegans, zebrafish, and the mouse, heparan sulfate (HS) biosynthesis is required for normal axon guidance, and mutations affecting Syndecan (Sdc), a transmembrane HSPG, disrupt axon guidance in Drosophila embryos. Glypicans, a family of glycosylphosphatidylinositol (GPI)-linked HSPGs, are expressed on axons and growth cones in vertebrates, but their role in axon guidance has not been determined. We demonstrate here that the Drosophila glypican Dally-like protein (Dlp) is required for proper axon guidance and visual-system function. Mosaic studies revealed that Dlp is necessary in both the retina and the brain for different aspects of visual-system assembly. Sdc mutants also showed axon guidance and visual-system defects, some that overlap with dlp and others that are unique. dlp+ transgenes were able to rescue some sdc visual-system phenotypes, but sdc+ transgenes were ineffective in rescuing dlp abnormalities. Together, these findings suggest that in some contexts HS chains provide the biologically critical component, whereas in others the structure of the protein core is also essential.
authors.affiliation: Department of Pediatrics, Developmental Biology Center, University of Minnesota, 321 Church St. SE, Minneapolis, Minnesota 55455, USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Rawson
authors.forename: Brian
authors.initials: B
authors.lastname: Dimitroff
authors.forename: Karl G
authors.initials: KG
authors.lastname: Johnson
authors.forename: Jaime M
authors.initials: JM
authors.lastname: Rawson
authors.forename: Xuecai
authors.initials: X
authors.lastname: Ge
authors.forename: David
authors.initials: D
authors.lastname: Van Vactor
authors.forename: Scott B
authors.initials: SB
authors.lastname: Selleck
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004594:Electrophysiology; D018507:Gene Expression Regulation, Developmental; D006497:Heparan Sulfate / Q000378:metabolism; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009024:Morphogenesis; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000648:ultrastructure; D011509:Proteoglycans / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D053667:Syndecans; D014795:Visual Pathways / Q000378:metabolism / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053667:Syndecans; C420997:dlp protein, Drosophila