Abstract
The mammalian spinal cord does not regenerate motor neurons that are lost as a result of injury or disease. Here we demonstrate that adult zebrafish, which show functional spinal cord regeneration, are capable of motor neuron regeneration. After a spinal lesion, the ventricular zone shows a widespread increase in proliferation, including slowly proliferating olig2-positive (olig2+) ependymo-radial glial progenitor cells. Lineage tracing in olig2:green fluorescent protein transgenic fish indicates that these cells switch from a gliogenic phenotype to motor neuron production. Numbers of undifferentiated small HB9+ and islet-1+ motor neurons, which are double labeled with the proliferation marker 5-bromo-2-deoxyuridine (BrdU), are transiently strongly increased in the lesioned spinal cord. Large differentiated motor neurons, which are lost after a lesion, reappear at 6-8 weeks after lesion, and we detected ChAT+/BrdU+ motor neurons that were covered by contacts immunopositive for the synaptic marker SV2. These observations suggest that, after a lesion, plasticity of olig2+ progenitor cells may allow them to generate motor neurons, some of which exhibit markers for terminal differentiation and integration into the existing adult spinal circuitry.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Bromodeoxyuridine
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Cell Count
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Cell Differentiation
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Cell Lineage
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Cell Proliferation
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Green Fluorescent Proteins / genetics
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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LIM-Homeodomain Proteins
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Microscopy, Electron
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Motor Neurons* / pathology
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Nerve Regeneration*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neuroglia / metabolism
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Neuroglia / pathology
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Oligodendrocyte Transcription Factor 2
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Phenotype
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Recombinant Fusion Proteins / genetics
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Spinal Cord / metabolism
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Spinal Cord / pathology
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Spinal Cord Injuries / pathology
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Spinal Cord Injuries / physiopathology*
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Stem Cells / metabolism
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Stem Cells / pathology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
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Zebrafish*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Homeodomain Proteins
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LIM-Homeodomain Proteins
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Mnx1 protein, zebrafish
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Nerve Tissue Proteins
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Oligodendrocyte Transcription Factor 2
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Recombinant Fusion Proteins
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Transcription Factors
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Zebrafish Proteins
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insulin gene enhancer binding protein Isl-1
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olig2 protein, zebrafish
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Green Fluorescent Proteins
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Bromodeoxyuridine