Caenorhabditis elegans neuronal regeneration is influenced by life stage, ephrin signaling, and synaptic branching

We previously reported functional regeneration of Caenorhabditis elegans motor neurons after femtosecond laser axotomy. We report here that multiple neuronal types can regrow after laser axotomy using a variety of lasers. The precise pattern of regrowth varies with cell type, stage of animal, and position of axotomy. Mechanosensory axons cut in late larval or adult stages displayed extensive regrowth, yet failed to reach their target area because of guidance errors in the anteroposterior axis. By contrast, mechanosensory axons cut in early larval stages regrew at the same rate but with fewer anteroposterior guidance errors, and were more likely to reach their target area. In adult animals lacking the VAB-1 Eph receptor tyrosine kinase, mechanosensory axon regrowth was more accurate than in the wild type, suggesting that guidance errors of regrowing touch neuron axons are the result of Eph signaling. Kinase-dependent and kinase-independent Eph signaling influenced outgrowth and guidance of regrowing touch neurons, respectively. Mechanosensory neurons regrew when severed proximal to their collateral synaptic branch but did not regrow when severed distal to the branch point. However, the distal axon could regrow if the branch is removed surgically at the same time as distal axotomy, or at a later time. The touch neuron synaptic branch point may act as a sorting area to regulate growth. These findings reveal that multiple influences affect regenerative growth in C. elegans neurons.