Exosomes have been reported to mediate transsynaptic Navitoclax manufacturer protein transfer in Drosophila NMJs ( Korkut et al., 2009), making the possibility that the same mechanism is deployed in the exchange of miRNAs very attractive. Another group of miRNAs involved at the Drosophila larval neuromuscular junction are the miR-310 cluster, miR-310–miR-313, but they appear to be playing an independently presynaptic role not requiring transsynaptic communication.

Loss of the cluster leads to a significant enhancement of neurotransmitter release, which can be rescued with temporally restricted expression of miR-310–miR-313 in larval presynaptic neurons ( Tsurudome et al., 2010). The Kinesin family member Khc-73 is a functional target for the cluster as its expression is increased in cluster mutants and reducing Khc-73 restores normal synaptic function. At later stages of the Drosophila life cycle during periods of tissue remodeling, there is coordinated selleck chemicals llc pre- and postsynaptic expression

of another conserved miRNA, let-7 ( Caygill and Johnston, 2008; Sokol et al., 2008). Loss of the fly let-7 complex (Let-7, miR-100, and miR-125) prevents the normal maturation of these NMJs as these animals metamorphose to adults, largely via regulation of the muscle transcription factor Abrupt. Investigation of miRNA function in many contexts indicates that they often act in concert with transcription factors to augment robustness or mediate feedback in the regulation of effector gene networks (reviewed by Peláez and Carthew, 2012). For example, in the C. elegans neuromuscular system, miR-1 controls both the expression of acetylcholine receptors and the muscle transcription

factor MEF-2 ( Simon et al., 2008). Interestingly, in this model, Phosphoprotein phosphatase MEF-2 is upstream of an unknown transsynaptic retrograde signal that appears to control presynaptic release properties. This miR-1/MEF-2 pathway highlights the intricate ongoing conversation between neurons and their synaptic partners as miR-1 regulates aspects of both pre- and postsynaptic functions at C. elegans neuromuscular junctions. Further exploration of miRNA-transcripton factor interactions in C. elegans has uncovered a role for miRNA in activity-dependent plasticity that is part of normal circuit remodeling during organismal development. In this work, the transcription factor hunchback-like 1 (HBL-1), orthologous to a gene that regulates the timing of neural progenitor fate determination in Drosophila, was found to be specifically expressed in a subset of motor neurons that actively remodel their synaptic connections during larval maturation ( Thompson-Peer et al., 2012). Interestingly, a change in neural activity induced a corresponding change in HBL-1 expression.