Dauer fate in a Caenorhabditis elegans Boolean network model

Cellular fates are determined by genes interacting across large, complex biological networks. A critical question is how to identify causal relationships spanning distinct signaling pathways and underlying organismal phenotypes. Here, we addressed this by constructing a Boolean model of a well-studied developmental network and analyzing information flows through the system. Depending on environmental signals Caenorhabditis elegans develop normally to sexual maturity or enter a reproductively delayed, developmentally quiescent ‘dauer’ state, progressing to maturity when the environment changes. The developmental network that starts with environmental signal and ends in the dauer/no dauer fate involves genes across 4 signaling pathways including cyclic GMP, Insulin/IGF-1, TGF-β and steroid hormone synthesis. We identified three stable motifs leading to normal development, each composed of genes interacting across the Insulin/IGF-1, TGF-Beta and steroid hormone synthesis pathways. Causal logic analysis identified a five gene cyclic subgraph summarizing the information flow from environmental signal to dauer fate. Perturbation analysis showed that a multifactorial insulin profile determined the stable motifs the system entered and interacted with daf-12 as the switchpoint driving the dauer/no dauer fate. Our results demonstrate how complex organismal systems can be distilled into abstract representations that permit full characterization of the causal relationships driving development. ### Competing Interest Statement The authors have declared no competing interest.