ZFIN ID: ZDB-PUB-041228-6
Axon Sorting in the Optic Tract Requires HSPG Synthesis by ext2 (dackel) and extl3 (boxer)
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.
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 (all 13) expand
PubMed: 15603738 Full text @ Neuron
FIGURES   (current status)
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.
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