Nematodes like C. elegans can survive the harshest of environmental conditions by adopting an alternative developmental program and entering into the dauer state. Dauer stage worms are reproductively immature. Entry into or exit from dauer in C. elegans is a carefully weighted decision taking into account factors such as food availability and population density, which is measured by pheromone levels in the population. Dauer development entails metabolic changes, such as increasing fat storage, and remodeling of tissues leading to the arrest of normal developmental programs, and a significant increase in lifespan. These metabolic and physiological changes are choreographed by changes in gene expression. One gene in particular,
daf-16, a homolog of the human FKHR and AFX genes, appears to play a major transcriptional regulatory role in this process. A second key gene, a receptor tyrosine kinase and insulin/IGF receptor ortholog,
daf-2, negatively regulates
daf-16. Mutations in
daf-2 result in a Dauer consititute phenotype and an extended lifespan. The C. elegans dauer stage larvae are often equated with the IJ infective juvenile stage larvae of parasitic nematodes.