Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish.
We analyzed the role of chondroitin sulfate (CS) glycosaminoglycans, putative inhibitors of axonal regeneration in mammals, in the regenerating visual pathway of adult zebrafish. In the adult, CS immunoreactivity was not detectable before or after an optic nerve crush in the optic nerve and tract but was constitutively present in developing and adult nonretinorecipient pretectal brain nuclei, where CSs may form a boundary preventing regenerating optic fibers from growing into these inappropriate locations. Enzymatic removal of CSs by chondroitinase ABC after optic nerve crush significantly increased the number of animals showing erroneous growth of optic axons into the nonretinorecipient magnocellular superficial/posterior pretectal nucleus (83% vs 42% in controls). In vitro, a substrate border of CSs, but not heparan sulfates, strongly repelled regenerating retinal axons from adult zebrafish. We conclude that CSs contribute to repellent axon guidance during regeneration of the optic projection in zebrafish.
Becker
Catherina G
CG
Zentrum für Molekulare Neurobiologie Hamburg, Universität Hamburg, D-20246 Hamburg, Germany. tcbecker@zmnh.uni-hamburg.de
Becker
Thomas
T
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000378:metabolism* / Q000494:pharmacology; D004027:Diencephalon / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives*; D009409:Nerve Crush; D009433:Neural Inhibition / Q000502:physiology; D009900:Optic Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism; D014795:Visual Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015027:Zebrafish
D019765:Chondroitin ABC Lyase; D002809:Chondroitin Sulfates; D006497:Heparan Sulfate; D008239:Lysine; D019063:Tenascin; C038142:chondroitin sulfate glycosaminoglycan; C074638:tenascin R; C013411:biocytin