An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans.
Mutations in daf-2 and age-1 cause a dramatic increase in longevity as well as developmental arrest at the dauer diapause stage in Caenorhabditis elegans. daf-2 and age-1 encode components of an insulin-like signaling pathway. Both daf-2 and age-1 act at a similar point in the genetic epistasis pathway for dauer arrest and longevity and regulate the activity of the daf-16 gene. Mutations in daf-16 cause a dauer-defective phenotype and are epistatic to the diapause arrest and life span extension phenotypes of daf-2 and age-1 mutants. Here we show that mutations in this pathway also affect fertility and embryonic development. Weak daf-2 alleles, and maternally rescued age-1 alleles that cause life span extension but do not arrest at the dauer stage, also reduce fertility and viability. We find that age-1(hx546) has reduced both maternal and zygotic age-1 activity. daf-16 mutations suppress all of the daf-2 and age-1 phenotypes, including dauer arrest, life span extension, reduced fertility, and viability defects. These data show that insulin signaling, mediated by DAF-2 through the AGE-1 phosphatidylinositol-3-OH kinase, regulates reproduction and embryonic development, as well as dauer diapause and life span, and that DAF-16 transduces these signals. The regulation of fertility, life span, and metabolism by an insulin-like signaling pathway is similar to the endocrine regulation of metabolism and fertility by mammalian insulin signaling.
Tissenbaum
H A
HA
Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Ruvkun
G
G
D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D005298:Fertility / Q000235:genetics; D051858:Forkhead Transcription Factors; D017238:Genes, Helminth / Q000235:genetics; D005838:Genotype; D015801:Helminth Proteins / Q000235:genetics*; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics; D012098:Reproduction / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics; D015053:Zygote / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D015801:Helminth Proteins; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D019869:Phosphatidylinositol 3-Kinases; C100662:AGE-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin