期刊
NEURON
卷 44, 期 6, 页码 947-960出版社
CELL PRESS
DOI: 10.1016/j.neuron.2004.11.029
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资金
- NCI NIH HHS [5U01-CA91290] Funding Source: Medline
- NCRR NIH HHS [RR12349] Funding Source: Medline
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 ext13, 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 ext13. dak;box double mutants show synthetic pathfinding phenotypes that phenocopy robot mutants, suggesting that Robot function requires HS in vivo; however, tract sorting does not require Robo function, since it is normal in robot 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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