Neuropeptides consist of short sequences of amino acids and function through G protein-coupled receptors and second messengers such as calcium and cAMP. Their involvement in processes such as learning, memory, and behaviour (e.g. locomotion and social behaviour) has widely been established1. However, their role in neuronal development, maintenance and regeneration has only started to be explored. Recent work has shown that the neuropeptide pigment dispersing factor (PDF) is involved in neuronal regeneration in C. elegans2. Mutant animals lacking PDF-1 peptides showed a 25% decrease of regrowth, 24 hours after axotomy in the mechanosensory PLM neuron. So far, it remains unknown where, when and how these neuropeptides stimulate regeneration. In C. elegans, neuronal regeneration after a laser-induced axotomy occurs through regrowth of the proximal fragment (attached to the cell soma), which is capable of reconnecting and eventually fusing with the distal fragment (separated from the cell soma). Whenever reconnection and fusion fail to occur, the distal fragment degenerates in stereotypical pattern. In order to elucidate the involvement of the PDF system in these events in C. elegans, we are characterizing the mechanosensory ALM and PLM neurons during development and regeneration in
pdf-1,
pdf-2 and
pdfr-1 mutant backgrounds. While ALM and PLM both develop normally, axonal regeneration and reconnection to the distal fragment is particularly compromised in the PLM neurons of
pdf-1 and
pdfr-1 mutant animals. Simultaneously, the distal fragments degenerate at a slightly faster rate. By expressing receptor fusion proteins under the
pdfr-1 promoter, we were able to confirm their expression in the mechanosensory neurons3,4 and postulate that the observed effects are controlled cell-autonomously. By using C. elegans as a model for neuronal development, maintenance and regeneration, we are now able to genetically dissect the pathways through which specific neuropeptides modulate these crucial biological processes.1 L. Frooninckx et al., Front. Endocrin. 3 (2012). 2 L. Chen et al., Neuron 71, 1043 (2011). 3 A. Barrios et al., Nat. Neurosci. 15, 1675 (2012). 4 T. Janssen et al., JBC 283, 15241 (2008).