Research ArticleNeuroscience

The lin-4 MicroRNA Targets the LIN-14 Transcription Factor to Inhibit Netrin-Mediated Axon Attraction

Sci. Signal.  12 Jun 2012:
Vol. 5, Issue 228, pp. ra43
DOI: 10.1126/scisignal.2002437

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Terminating Axonal Pathfinding

As axons approach their targets, they need to stop pathfinding and form synapses, a process controlled by signals from the target. Using genetic interactions, overexpression studies, and reporter gene analysis, Zou et al. showed that a microRNA controlled the timing of axonal outgrowth termination. In Caenorhabditis elegans, the microRNA lin-4 was specifically produced in the anterior ventral microtubule (AVM) neurons that respond to the attractive guidance cue UNC-6 (netrin in vertebrates). Reporter analysis indicated that expression of lin-14, which encodes a transcription factor and which has lin-4 binding sites in the 3′ untranslated region of the transcript, was inhibited by lin-4, leading to a reduction in the responsiveness of the axon to UNC-6 and reduced signaling by the UNC-6 receptor UNC-40 (DCC in vertebrates). These results suggest that a microRNA triggers a developmental switch in response to guidance cues that is necessary for the neuron to change from pathfinding to synapse formation.