Open Close
Nesler, K.R., Sand, R.I., Symmes, B.A., Pradhan, S.J., Boin, N.G., Laun, A.E., Barbee, S.A. (2013). The miRNA Pathway Controls Rapid Changes in Activity-Dependent Synaptic Structure at the Drosophila melanogaster Neuromuscular Junction.  PLoS ONE 8(7): e68385.
FlyBase ID
Publication Type
Research paper

It is widely accepted that long-term changes in synapse structure and function are mediated by rapid activity-dependent gene transcription and new protein synthesis. A growing amount of evidence suggests that the microRNA (miRNA) pathway plays an important role in coordinating these processes. Despite recent advances in this field, there remains a critical need to identify specific activity-regulated miRNAs as well as their key messenger RNA (mRNA) targets. To address these questions, we used the larval Drosophila melanogaster neuromuscular junction (NMJ) as a model synapse in which to identify novel miRNA-mediated mechanisms that control activity-dependent synaptic growth. First, we developed a screen to identify miRNAs differentially regulated in the larval CNS following spaced synaptic stimulation. Surprisingly, we identified five miRNAs (miRs-1, -8, -289, -314, and -958) that were significantly downregulated by activity. Neuronal misexpression of three miRNAs (miRs-8, -289, and -958) suppressed activity-dependent synaptic growth suggesting that these miRNAs control the translation of biologically relevant target mRNAs. Functional annotation cluster analysis revealed that putative targets of miRs-8 and -289 are significantly enriched in clusters involved in the control of neuronal processes including axon development, pathfinding, and growth. In support of this, miR-8 regulated the expression of a wingless 3'UTR (wg 3' untranslated region) reporter in vitro. Wg is an important presynaptic regulatory protein required for activity-dependent axon terminal growth at the fly NMJ. In conclusion, our results are consistent with a model where key activity-regulated miRNAs are required to coordinate the expression of genes involved in activity-dependent synaptogenesis.

PubMed ID
PubMed Central ID
PMC3699548 (PMC) (EuropePMC)
Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    PLoS ONE
    PLoS ONE
    Publication Year
    Data From Reference