Transcriptional enhancement of Smn levels in motoneurons is crucial for proper axon morphology in zebrafish.
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.
Department of Biological Sciences, National University of Singapore, Singapore.|NUS Centre for BioImaging Sciences (CBIS), Singapore.
Zoltán
Z
Spiró
Department of Biological Sciences, National University of Singapore, Singapore.|NUS Centre for BioImaging Sciences (CBIS), Singapore.
Angela
A
Koh
Department of Biological Sciences, National University of Singapore, Singapore.|NUS Centre for BioImaging Sciences (CBIS), Singapore.
Shermaine
S
Tay
Department of Biological Sciences, National University of Singapore, Singapore.|NUS Centre for BioImaging Sciences (CBIS), Singapore.
Kelvin
K
See
Department of Biological Sciences, National University of Singapore, Singapore.|NUS Centre for BioImaging Sciences (CBIS), Singapore.
Christoph
C
Winkler
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons; D017403:In Situ Hybridization / Q000379:methods; D009046:Motor Neurons / Q000378:metabolism*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish
D055533:Survival of Motor Neuron 1 Protein; C526474:smn1 protein, zebrafish