Role of Wnt signaling in asymmetrical neurite pruning in Caenorhabditis elegans

Developmental neurite pruning is a phenomenon widely observed in different organisms including humans. Through this process, neurons selectively remove exuberant neurites by pruning to form a proper neurocircuit. Some neurites are pruned base on the competition of neuronal input, while others undergo stereotyped pruning which is controlled by morphogenic cues. We found that in Caenorhabditis elegans, a cholinergic motor neuron, PDB, undergoes stereotyped neurite pruning. During PDB development, we observed two posterior branches that are stereotypically pruned. Time-lapse imaging showed that these posterior branches are retracted while the anterior branch is extending. We also found a posteriorly expressed Wnt, LIN-44, and its receptor LIN-17/Frizzled (Fz) are responsible for the pruning of the posterior neurites. In lin-44 and lin-17 mutant animals, the posterior neurites often failed to be pruned. Furthermore, we discovered that the activation of LIN-44/Wnt is gradient independent, and membrane-tethered lin-44 is sufficient to induce asymmetrical posterior neurite pruning. LIN-17 and its downstream DSH-1/Dishevelled (Dsh/Dvl) proteins are recruited to the posterior neurites while either wildtype or membrane-tethered lin-44 is expressed. Our results showed a novel contact-dependent role of Wnt in asymmetric neurite pruning.Science, Faculty ofZoology, Department ofGraduat