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

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Spiró Z,Koh A,Tay S,See K,Winkler C

doi

10.1038/srep27470

subject

Has Abstract

pub_date

2016-06-07 00:00:00

pages

27470

issn

2045-2322

pii

srep27470

journal_volume

6

pub_type

杂志文章

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