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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Video-Audio Media
MeSH terms
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Adenylyl Imidodiphosphate / pharmacology
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Animals
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Animals, Genetically Modified
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Cell Movement / drug effects
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Cell Movement / genetics
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Cell Movement / physiology*
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Coloring Agents / metabolism
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Embryo, Nonmammalian
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Functional Laterality / physiology
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / genetics
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Gene Expression Regulation, Developmental / physiology*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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Heparitin Sulfate / metabolism
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In Vitro Techniques
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Microscopy, Confocal
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Morpholinos / pharmacology
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Mutation / genetics
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Nerve Degeneration / genetics
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Nerve Degeneration / pathology
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Nerve Degeneration / surgery
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Proteoglycans / genetics
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Proteoglycans / metabolism*
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Retina / cytology
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Retinal Ganglion Cells / transplantation
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Time Factors
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
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Visual Pathways / embryology
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Visual Pathways / physiology*
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Zebrafish
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
Substances
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Coloring Agents
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HSP70 Heat-Shock Proteins
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Morpholinos
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Proteoglycans
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Tumor Suppressor Protein p53
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Zebrafish Proteins
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dackel protein, zebrafish
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enhanced green fluorescent protein
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heat-shock protein 70.1
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tp53 protein, zebrafish
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Green Fluorescent Proteins
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Adenylyl Imidodiphosphate
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Heparitin Sulfate