PUBLICATION

Proteoglycan-mediated axon degeneration corrects pretarget topographic sorting errors

Authors
Poulain, F.E., and Chien, C.B.
ID
ZDB-PUB-130422-12
Date
2013
Source
Neuron   78(1): 49-56 (Journal)
Registered Authors
Chien, Chi-Bin, Poulain, Fabienne
Keywords
none
MeSH Terms
  • Cell Movement/drug effects
  • Cell Movement/genetics
  • Cell Movement/physiology*
  • In Vitro Techniques
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • Mutation/genetics
  • Retina/cytology
  • Visual Pathways/embryology
  • Visual Pathways/physiology*
  • Embryo, Nonmammalian
  • Proteoglycans/genetics
  • Proteoglycans/metabolism*
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism
  • Zebrafish
  • Retinal Ganglion Cells/transplantation
  • Nerve Degeneration/genetics
  • Nerve Degeneration/pathology
  • Nerve Degeneration/surgery
  • Functional Laterality/physiology
  • Microscopy, Confocal
  • Adenylyl Imidodiphosphate/pharmacology
  • Time Factors
  • Coloring Agents/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • HSP70 Heat-Shock Proteins/genetics
  • HSP70 Heat-Shock Proteins/metabolism
  • Morpholinos/pharmacology
  • Heparitin Sulfate/metabolism
  • Animals
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Expression Regulation, Developmental/genetics
  • Gene Expression Regulation, Developmental/physiology*
  • Animals, Genetically Modified
PubMed
23583107 Full text @ Neuron
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.

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