The daf-7(e1372) mutation rescues dauer formation defects seen in C. elegans unc-33 mutants.

Collapsin response mediator protein-2 (CRMP2) in humans, UNC-33 in C. elegans, is a molecule that mediates axonal outgrowth and stability. UNC-33/CRMP2 has been hypothesized as a potential drug target for treating Alzheimer's and other neurodegenerative diseases, which can often be attributed in part to aging. In aging, CRMP2 becomes hyperphosphorylated, which decreases the protein's functionality, destabilizes the cellular skeleton, and contributes to neurodegeneration. In C. elegans, aging can be slowed by entering dauer diapause; a non-aging developmental stage turned on when the DAF-7/TGFß signaling pathway is silenced in response to environmental stressors. In our laboratory, we discovered that unc-33 mutants are unable to form dauers in response to environmental stressors, but the mechanism behind this is still unknown. Here, we present a study that investigates whether a mutation in the daf-7 gene which leads to a temperature sensitive constitutive dauer phenotype can rescue phenotypes characteristic of unc-33 mutants. To this end, we created unc-33; daf-7 double mutants and quantified proper dauer formation after exposure to unfavorable environmental conditions. In addition, we tested how the introduction of the daf-7 mutation would affect the locomotion of the double mutants on an agar plate and a liquid medium. Furthermore, we examined axonal elongation of the double mutants using a transgene, juIs76, which expresses GFP in GABAergic motor neurons. Our analysis of unc-33; daf-7 double mutants showed that introducing the daf-7 mutation into an unc-33 mutant rescued dauer formation. However, further studies revealed that the unc-33; daf-7 double mutants had defects in axonal outgrowth of their D-type motor neuron which had been previously seen in unc-33 single mutants and impaired locomotion. Based on these results, we concluded that unc-33 mutants might have a problem suppressing DAF-7 signaling under unfavorable environmental conditions, leading to the activation of reproductive programs and the development of adults instead of dauers.

UNC-33L partially rescues life span and locomotion defects in unc-33 mutants but fails to rescue dauer formation defects.

Herein, we tested the ability of UNC-33L to rescue dauer formation, lifespan, and locomotion defects of unc-33(mn407) mutants. Results show that the presence of UNC-33L does not rescue the defective dauer phenotype in unc-33(mn407) mutants. However, UNC-33L significantly rescued premature death and uncoordinated locomotion in young unc-33(mn407) adults. The degree of UNC-33L-mediated rescue was less noticeable as the nematodes aged, denoting that both age and the presence of UNC-33L interact in the production of the phenotypes.