PUBLICATION

Transcriptional enhancement of Smn levels in motoneurons is crucial for proper axon morphology in zebrafish

Authors
Spiró, Z., Koh, A., Tay, S., See, K., Winkler, C.
ID
ZDB-PUB-160610-12
Date
2016
Source
Scientific Reports   6: 27470 (Journal)
Registered Authors
Winkler, Christoph
Keywords
Molecular medicine, Neurodegeneration
MeSH Terms
  • In Situ Hybridization/methods
  • Axons*
  • Zebrafish
  • Transcription, Genetic*
  • Motor Neurons/metabolism*
  • Animals, Genetically Modified
  • Animals
  • Survival of Motor Neuron 1 Protein/genetics*
  • Survival of Motor Neuron 1 Protein/metabolism
(all 9)
PubMed
27273160 Full text @ Sci. Rep.
Abstract
An unresolved mystery in the field of spinal muscular atrophy (SMA) is why a reduction of the ubiquitously expressed Smn protein causes defects mostly in motoneurons. We addressed the possibility that this restricted vulnerability stems from elevated Smn expression in motoneurons. To explore this, we established an ex vivo zebrafish culture system of GFP-marked motoneurons to quantitatively measure Smn protein and smn mRNA levels as well as promoter activity in motoneurons versus other cell types. Importantly, we uncovered that Smn levels are elevated in motoneurons by means of transcriptional activation. In addition, we identified the ETS family transcription factor Etv5b to be responsible for increased smn transcription in motoneurons. Moreover, we established that the additional supply of Smn protein in motoneurons is necessary for proper axonogenesis in a cell-autonomous manner. These findings demonstrate the reliance of motoneurons on more Smn, thereby adding a novel piece of evidence for their increased vulnerability under SMA conditions.
Genes / Markers
Figures
Figure Gallery (7 images)
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
EGFPns10Tgstandard conditionsPrim-5IFL
etv5bWTstandard conditionsPrim-5ISH
mCherryns12Tg + MO2-etv5bstandard conditionsPrim-5IHC
mCherryns12Tg + MO2-etv5bstandard conditionsPrim-5IHC
1 - 4 of 4
Show
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO2-etv5bstandard conditionsPrim-5
WT + MO2-etv5bstandard conditionsPrim-5
WT + MO2-etv5bstandard conditionsPrim-5
ns12Tg + MO2-etv5bstandard conditionsPrim-5
ns12Tg + MO2-etv5bstandard conditionsPrim-5
1 - 5 of 5
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ns10TgTransgenic Insertion
    ns11TgTransgenic Insertion
      ns12TgTransgenic Insertion
        vu17TgTransgenic Insertion
          1 - 4 of 4
          Show
          Human Disease / Model
          Human Disease Fish Conditions Evidence
          spinal muscular atrophyTAS
          1 - 1 of 1
          Show
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          etv5bMO2-etv5bMRPHLNO
          smn1MO1-smn1MRPHLNO
          1 - 2 of 2
          Show
          Fish
          Fish
          ns10Tg
          ns11Tg
          ns12Tg + MO2-etv5b
          WT
          WT + MO2-etv5b
          1 - 5 of 5
          Show
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          mCherryEFGmCherry
          1 - 2 of 2
          Show
          Mapping
          No data available
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          Citation
          Spiró, Z., Koh, A., Tay, S., See, K., Winkler, C. (2016) Transcriptional enhancement of Smn levels in motoneurons is crucial for proper axon morphology in zebrafish. Scientific Reports. 6:27470.