PUBLICATION

Optic nerve regeneration in larval zebrafish exhibits spontaneous capacity for retinotopic but not tectum specific axon targeting

Authors
Harvey, B.M., Baxter, M., Granato, M.
ID
ZDB-PUB-190621-8
Date
2019
Source
PLoS One   14: e0218667 (Journal)
Registered Authors
Granato, Michael
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Axons/physiology*
  • Green Fluorescent Proteins/genetics
  • Green Fluorescent Proteins/metabolism
  • LIM-Homeodomain Proteins/genetics
  • LIM-Homeodomain Proteins/metabolism
  • Larva
  • Nerve Regeneration/physiology*
  • Optic Nerve/physiopathology*
  • Optic Nerve Injuries/rehabilitation
  • Optic Nerve Injuries/veterinary
  • Retinal Ganglion Cells/physiology*
  • Superior Colliculi/physiopathology*
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish/growth & development
  • Zebrafish/physiology*
(all 18)
PubMed
31220164 Full text @ PLoS One
Abstract
In contrast to mammals, retinal ganglion cells (RGC) axons of the optic nerve even in mature zebrafish exhibit a remarkable capacity for spontaneous regeneration. One constraint of using adult zebrafish is the limited ability to visualize the regeneration process in live animals. To dynamically visualize and trace the degree of target specific optic nerve regeneration, we took advantage of the optical transparency still preserved in post developmental larval zebrafish. We developed a rapid and robust assay to physically transect the larval optic nerve and find that by 96 hours post injury RGC axons have robustly regrown onto the optic tectum. We observe functional regeneration by 8 days post injury, and demonstrate that similar to adult zebrafish, optic nerve transection in larval zebrafish does not prominently induce cell death or proliferation of RGC neurons. Furthermore, we find that partial optic nerve transection results in axonal growth predominantly to the original, contralateral tectum, while complete transection results in innervation of both the correct contralateral and 'incorrect' ipsilateral tectum. Axonal tracing reveals that although regenerating axons innervate the 'incorrect' ipsilateral tectum, they successfully target their topographically appropriate synaptic areas. Combined, our results validate post developmental larval zebrafish as a powerful model for optic nerve regeneration, and reveal intricate mechanistic differences between axonal growth, midline guidance and synaptic targeting during zebrafish optic nerve regeneration.
Genes / Markers
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zc7TgTransgenic Insertion
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    Human Disease / Model
    Sequence Targeting Reagents
    Fish
    Antibodies
    Orthology
    Engineered Foreign Genes
    Marker Marker Type Name
    GFPEFGGFP
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    Citation
    Harvey, B.M., Baxter, M., Granato, M. (2019) Optic nerve regeneration in larval zebrafish exhibits spontaneous capacity for retinotopic but not tectum specific axon targeting. PLoS One. 14:e0218667.