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
-
- Animals
- Animals, Genetically Modified
- Axons*
- In Situ Hybridization/methods
- Motor Neurons/metabolism*
- Survival of Motor Neuron 1 Protein/genetics*
- Survival of Motor Neuron 1 Protein/metabolism
- Transcription, Genetic*
- Zebrafish
- PubMed
- 27273160 Full text @ Sci. Rep.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping