PUBLICATION

Axon Sorting in the Optic Tract Requires HSPG Synthesis by ext2 (dackel) and extl3 (boxer)

Authors
Lee, J.S., von der Hardt, S., Rusch, M.A., Stringer, S.E., Stickney, H.L., Talbot, W.S., Geisler, R., Nüsslein-Volhard, C., Selleck, S.B., Chien, C.B., and Roehl, H.
ID
ZDB-PUB-041228-6
Date
2004
Source
Neuron   44(6): 947-960 (Journal)
Registered Authors
Chien, Chi-Bin, Geisler, Robert, Lee, Jeong-Soo, Nüsslein-Volhard, Christiane, Roehl, Henry, Stickney, Heather, Talbot, William S., von der Hardt, Sophia
Keywords
none
MeSH Terms
  • Animals
  • Axons/metabolism*
  • Heparan Sulfate Proteoglycans/biosynthesis*
  • Heparan Sulfate Proteoglycans/genetics
  • Molecular Sequence Data
  • N-Acetylglucosaminyltransferases/biosynthesis
  • N-Acetylglucosaminyltransferases/genetics
  • N-Acetylglucosaminyltransferases/physiology*
  • Retinal Ganglion Cells/metabolism
  • Visual Pathways/embryology
  • Visual Pathways/metabolism*
  • Zebrafish
  • Zebrafish Proteins/physiology*
PubMed
15603738 Full text @ Neuron
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes