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PMID:15603738

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Citation

Lee, JS, von der Hardt, S, Rusch, MA, Stringer, SE, Stickney, HL, Talbot, WS, Geisler, R, Nüsslein-Volhard, C, Selleck, SB, Chien, CB and Roehl, H (2004) Axon sorting in the optic tract requires HSPG synthesis by ext2 (dackel) and extl3 (boxer). Neuron 44:947-60

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.

Links

PubMed Online version:10.1016/j.neuron.2004.11.029

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:F1QUC2

involved_in

GO:0030516: regulation of axon extension

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-872

P

Seeded From UniProt

complete

DANRE:F1QUC2

involved_in

GO:0015012: heparan sulfate proteoglycan biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-872

P

Seeded From UniProt

complete

DANRE:F1QUC2

enables

GO:0050509: N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q93063

F

Seeded From UniProt

complete

DANRE:F1QUC2

involved_in

GO:0035138: pectoral fin morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-872

P

Seeded From UniProt

complete

DANRE:Q5U7A7

involved_in

GO:0030516: regulation of axon extension

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-872

P

Seeded From UniProt

complete

DANRE:Q5U7A7

involved_in

GO:0015012: heparan sulfate proteoglycan biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-872

P

Seeded From UniProt

complete

DANRE:Q5U7A7

enables

GO:0050509: N-acetylglucosaminyl-proteoglycan 4-beta-glucuronosyltransferase activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:Q93063

F

Seeded From UniProt

complete

DANRE:Q5U7A7

involved_in

GO:0035138: pectoral fin morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-872

P

Seeded From UniProt

complete

DANRE:Q5U7D2

involved_in

GO:0030516: regulation of axon extension

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-1172

P

Seeded From UniProt

complete

DANRE:Q5U7D2

involved_in

GO:0015012: heparan sulfate proteoglycan biosynthetic process

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-1172

P

Seeded From UniProt

complete

DANRE:Q5U7D2

enables

GO:0001888: glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity

ECO:0000250: sequence similarity evidence used in manual assertion

UniProtKB:O43909

F

Seeded From UniProt

complete

DANRE:Q5U7D2

involved_in

GO:0035138: pectoral fin morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-GENO-980202-1172

P

Seeded From UniProt

complete

See also

References

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