Recently, we found that multiple thermosensory mutants, including
tax-2 mutants, which lack a subunit of the neuronal cyclic-nucleotide gated channel, lived even shorter than wild type at 25 deg C (the warm temperature) (1). The short lifespan of
tax-2 mutants at 25 deg C was completely suppressed by a null mutation in
daf-12/NHR (nuclear hormone receptor) gene (1). From these and other molecular genetics data, we proposed that thermosensory AFD neurons moderate the effect that increased temperature otherwise have on the lifespan of C. elegans by changing the activity of the transcription factor DAF-12 (1). In addition to the effects on aging, the thermosensory
tax-2 mutations cause a constitutive dauer phenotype at 27 degC (2). Interestingly,
daf-12 mutation suppresses this dauer phenotype (2) as well as the short 25 deg C-lifespan phenotype caused by
tax-2 mutations (1). Thus, we hypothesized that other mutations that suppress the 27 deg C dauer phenotype of
tax-2 mutations may also suppress the lifespan phenotype as well. We first tested whether known dauer suppressor mutations suppressed the 27 deg C dauer phenotype of the
tax-2 mutants. We confirmed that the dauer phenotype of the
tax-2 mutants was significantly suppressed by
daf-12 mutation. However,
daf-3,
daf-5,
scd-1,
scd-2 or
scd-3 mutations, which have been shown to suppress dauer formation of various dauer-constitutive mutants, did not affect the
tax-2 mutants'' dauer phenotype. Since only a few known dauer suppressor mutants suppressed the
tax-2 mutants'' dauer phenotype, these data suggest that a dauer-suppressor mutagenesis screening may produce novel mutants rather than already identified mutants. We then carried out EMS mutagenesis screening for mutants that suppressed constitutive dauer phenotype of
tax-2 mutants at 27 deg C. We found and confirmed 7 tds (
tax-2 dauer suppressor) mutants from the screening. All of them were recessive mutants. We will carry out complementation and mapping analyses. We will also determine whether any of the tds mutants suppress lifespan phenotypes of the
tax-2 mutants. Our goal is to identify new components involved in the longevity response to temperature and to understand how the AFD neurons affect DAF-12 activity to regulate lifespan at high temperature. (1) Lee and Kenyon, 2009, Curr Biol (in press) (2) Ailion and Thomas, 2000, Genetics.