Actin polymerization plays an important role in cell migration and axon/dendrite outgrowth. Both attractive and repulsive signals regulate actin-mediated protrusions. Here we show that actin plays a key role in the process of dendritic self-avoidance. Dendrites arising from a single neuron rarely overlap due to contact-dependent retraction. We have observed this phenomenon in the highly branched C. elegans nociceptive neuron, PVD, in which tertiary sister dendrites retract upon mutual contact. We have previously shown that PVD self-avoidance is mediated by the short -range diffusible cue, UNC-6/Netrin and its receptors, UNC-40/DCC and UNC-5. Our observations show that actin is enriched in these retracting tertiary dendrites. A genetic survey of candidate UNC-6 downstream components established that the actin polymerizing protein, UNC-34/Ena/VASP is also required for PVD self-avoidance. We used ‘pseudo-TIRF’ microscopy to detect a burst of actin accumulation and UNC-34 localization at the tips of retracting PVD dendrites immediately after contact. These findings suggest the paradoxical idea that UNC-34-mediated growth of nascent actin filaments is required for dendrite retraction. This model may be explained by the observation that the non-muscle myosin, NMY-1, is necessary for PVD dendrite retraction and could mediate this effect by retrograde flow. Genetic studies are consistent with NMY-1 functioning in the same pathway as UNC-34. Together, these data suggest that UNC-6/Netrin signaling triggers local assembly of new actin filaments, which then engage NMY-1 to elicit dendrite retraction. In addition to describing the first cell biological mechanism of dendrite self-avoidance, we also suggest that nascent actin assembly and retrograde flow could be required for axonal growth cone repulsion. .
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