The downregulation of the insulin pathway during the dauer state protects mechanosensory neurons from degeneration triggered by hyperactivated degenerins (
mec-4d and
deg-1). We proposed that this protection was due to metabolic changes such as caloric restriction and enhanced expression of antioxidants (Calixto et al., 2012). We found that at the time of dauer entry 36 to 48 hours after food deprivation, many
mec-4d expressing touch receptor neurons (TRNs) had already degenerated. However, one week after dauer entry the TRNs appear functionally and morphologically intact. This raised the question whether the neuronal protection observed in dauers and mutants of the insulin pathway were due to the regeneration of neurons undergoing degeneration. We found that degenerating TRNs in a
daf-2 mutant background showed growth cones and reinforcement of the neuronal processes. To test whether diapause formation and DAF-2 downregulation promoted neuronal regeneration of somas and axons, we scored the integrity of
mec-4d expressing AVM TRN at dauer entry and thereafter every 24 hours to assess the regrowth of processes. We found that the dauer state not only halts the degeneration process but also causes regeneration of the TRNs expressing MEC-4d. To test whether
daf-2 downregulation induced regeneration of the touch receptor neurons we performed combinatorial
daf-2(RNAi) with genes that are required for regeneration in mechanosensory neurons (Yan et al., 2009).
dlk-1(RNAi) reduced the
daf-2(RNAi) induced protection from degeneration while
dlk-1(RNAi) alone was no different from controls. Furthermore, reduction of
efa-6, known to prevent regeneration (Chen et al., 2011), protects from the
mec-4d induced degeneration and enhances the protection provided by
daf-2(RNAi). These results suggest that repression of genes that inhibit regrowth may override the deleterious effects of persistant prodegenerative stimuli and that dauer formation promotes regeneration of neurons.