title: Proteoglycan-mediated axon degeneration corrects pretarget topographic sorting errors.
abstract: Proper arrangement of axonal projections into topographic maps is crucial for brain function, especially in sensory systems. An important mechanism for map formation is pretarget axon sorting, in which topographic ordering of axons appears in tracts before axons reach their target, but this process remains poorly understood. Here, we show that selective axon degeneration is used as a correction mechanism to eliminate missorted axons in the optic tract during retinotectal development in zebrafish. Retinal axons are not precisely ordered during initial pathfinding but become corrected later, with missorted axons selectively fragmenting and degenerating. We further show that heparan sulfate is required non-cell-autonomously to correct missorted axons and that restoring its synthesis at late stages in a deficient mutant is sufficient to restore topographic sorting. These findings uncover a function for developmental axon degeneration in ordering axonal projections and identify heparan sulfate as a key regulator of that process.
authors.affiliation: University of Utah, Neurobiology and Anatomy Department, Salt Lake City, UT 84132, USA. fpoulain@genetics.utah.edu
authors.forename: Fabienne E
authors.initials: FE
authors.lastname: Poulain
authors.forename: Chi-Bin
authors.initials: CB
authors.lastname: Chien
mesh_terms: D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D004396:Coloring Agents / Q000378:metabolism; D004625:Embryo, Nonmammalian; D007839:Functional Laterality / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D060172:Morpholinos / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology; D012165:Retinal Ganglion Cells / Q000637:transplantation; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014795:Visual Pathways / Q000196:embryology / Q000502:physiology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000266:Adenylyl Imidodiphosphate; D004396:Coloring Agents; D049452:Green Fluorescent Proteins; D018840:HSP70 Heat-Shock Proteins; D006497:Heparan Sulfate; D060172:Morpholinos; D011509:Proteoglycans; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C416220:dackel protein, zebrafish; C485184:enhanced green fluorescent protein; C081884:heat-shock protein 70.1; C571228:tp53 protein, zebrafish