Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer)

Jeong Soo Lee, Sophia Von Der Hardt, Melissa A. Rusch, Sally E. Stringer, Heather L. Stickney, William S. Talbot, Robert Geisler, Christiane Nüsslein-Volhard, Scott B. Selleck, Chi Bin Chien, Henry Roehl

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130 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)947-960
Number of pages14
JournalNeuron
Volume44
Issue number6
DOIs
StatePublished - Dec 16 2004

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    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., & Roehl, H. (2004). Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron, 44(6), 947-960. https://doi.org/10.1016/j.neuron.2004.11.029