TY - JOUR
T1 - Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer)
AU - Lee, Jeong Soo
AU - Von Der Hardt, Sophia
AU - Rusch, Melissa A.
AU - Stringer, Sally E.
AU - Stickney, Heather L.
AU - Talbot, William S.
AU - Geisler, Robert
AU - Nüsslein-Volhard, Christiane
AU - Selleck, Scott B.
AU - Chien, Chi Bin
AU - Roehl, Henry
N1 - Funding Information:
We thank Silke Geiger-Rudolph for providing fixed box embryos; Louis Ross for technical support; and members of the Chien, Geisler, and Nüsslein-Volhard laboratories for advice and help. Thanks to Michael Granato for suggesting the use of dCAPS primers. We thank Christa Lanz, Günter Raddatz, and Stephan Schuster for shotgun sequencing the BZ2B14 PAC; and Gerg-Jörg Rauch and Axel Küchler for the initial mapping of dak. We also thank Maureen Condic for comments and discussion of the manuscript. This work was supported by a grant from the NSF (to C.-B.C.); by a Wellcome Trust grant (072346/Z/03/Z); by the Max Planck Society (to H.R.); and by NCI 5U01-CA91290 (to S.B.S). This work was also supported by a graduate fellowship from HHMI (to H.L.S.); NIH grant RR12349 (to W.S.T.); and by the DHGP (to R.G.).
PY - 2004/12/16
Y1 - 2004/12/16
N2 - 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.
AB - 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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U2 - 10.1016/j.neuron.2004.11.029
DO - 10.1016/j.neuron.2004.11.029
M3 - Article
C2 - 15603738
AN - SCOPUS:10444270932
SN - 0896-6273
VL - 44
SP - 947
EP - 960
JO - Neuron
JF - Neuron
IS - 6
ER -