How organisms make stable developmental or physiological decisions, meaning that all cells of the body reach a
consensus even when exposed to ambiguous environmental stimuli, is of fundamental interest in biology. The dauer
stage of Caenorhabditis elegans, an alternative larval stage of diapause triggered by food limitation and crowding,
provides excellent conditions for addressing this question. Strong mutations in the gene coding for the insulin/IGF
receptor DAF-2 result in constitutive dauer arrest, but daf-2 genetic mosaics are not phenotypically mosaic. Instead
all cells reach a consensus and animals either develop into dauers or adults. Thus a mechanism exists to ensure that
all cells reach a consensus in their developmental fate. How diverse cell signaling cascades are integrated to ensure
that all cells reach a consensus is unclear. I propose to identify novel genes important in the consensus of
developmental fates. Animals carrying a weaker daf-2 mutation have an indeterminant developmental fate: about
half of the worms become dauers and half develop into adults. I will look for mutations that prevent the cells in
these animals from reaching a consensus, and cause them to have mixtures of dauer and non-dauer cells. A dauer-
specific GFP-tagged reporter line will be used to screen for RNAi mutants with a defective consensus mechanism,
in which the reporter is expressed in some but not all cells. Expression of the newly identified genes as well as
genes known to affect the dauer vs. non-dauer decision will be analyzed via live-imaging of the animals as they
undergo dauer formation. Additionally, DAF-2 signaling regulates aging of the animal. Therefore I will test
whether the identified mutants also affect the consensus mechanism in life span regulation. Together this will help
to unravel the mechanism that ensures organism-wide consensus of developmental decisions. Furthermore, our
results will help to reveal the function of evolutionarily-conserved endocrine pathways that function not only in
development but also in aging and diseases such as diabetes and cancer.