title: Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer).
abstract: Retinal ganglion cell (RGC) axons are topographically ordered in the optic tract according to their retinal origin. In zebrafish dackel (dak) and boxer (box) mutants, some dorsal RGC axons missort in the optic tract but innervate the tectum topographically. Molecular cloning reveals that dak and box encode ext2 and extl3, glycosyltransferases implicated in heparan sulfate (HS) biosynthesis. Both genes are required for HS synthesis, as shown by biochemical and immunohistochemical analysis, and are expressed maternally and then ubiquitously, likely playing permissive roles. Missorting in box can be rescued by overexpression of extl3. dak;box double mutants show synthetic pathfinding phenotypes that phenocopy robo2 mutants, suggesting that Robo2 function requires HS in vivo; however, tract sorting does not require Robo function, since it is normal in robo2 null mutants. This genetic evidence that heparan sulfate proteoglycan function is required for optic tract sorting provides clues to begin understanding the underlying molecular mechanisms.
authors.affiliation: Department of Neurobiology and Anatomy, University of Utah, 20 North 1900 East, Salt Lake City, Utah 84103, USA.
authors.forename: Jeong-Soo
authors.initials: JS
authors.lastname: Lee
authors.forename: Sophia
authors.initials: S
authors.lastname: von der Hardt
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Rusch
authors.forename: Sally E
authors.initials: SE
authors.lastname: Stringer
authors.forename: Heather L
authors.initials: HL
authors.lastname: Stickney
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
authors.forename: Robert
authors.initials: R
authors.lastname: Geisler
authors.forename: Christiane
authors.initials: C
authors.lastname: Nüsslein-Volhard
authors.forename: Scott B
authors.initials: SB
authors.lastname: Selleck
authors.forename: Chi-Bin
authors.initials: CB
authors.lastname: Chien
authors.forename: Henry
authors.initials: H
authors.lastname: Roehl
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D014795:Visual Pathways / Q000196:embryology / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*; D000099065:Exostosin 2
chemical_list: C484685:Extl3 protein, mouse; D019812:Heparan Sulfate Proteoglycans; D029961:Zebrafish Proteins; C416220:dackel protein, zebrafish; D017351:N-Acetylglucosaminyltransferases; D000099065:Exostosin 2