Motor neuron regeneration in adult zebrafish.
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.
Reimer
Michell M
MM
Centre for Neuroscience Research, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, United Kingdom.
Sörensen
Inga
I
Kuscha
Veronika
V
Frank
Rebecca E
RE
Liu
Chong
C
Becker
Catherina G
CG
Becker
Thomas
T
D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D008854:Microscopy, Electron; D009046:Motor Neurons / Q000473:pathology; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D000076104:Oligodendrocyte Transcription Factor 2; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C531385:Mnx1 protein, zebrafish; C063843:insulin gene enhancer binding protein Isl-1; C465361:olig2 protein, zebrafish