Heterochronic genes control the stage-specific initiation and expression of the dauer larva developmental program in Caenorhabditis elegans.

We report that a stage-specific developmental program, dauer larva formation, is temporally regulated by four heterochronic genes, lin-4, lin-14, lin-28, and lin-29. The effects of mutations in these four genes on dauer larva formation have revealed that they regulate two different processes of dauer larva formation: (1) a decision specifying the larval stage at which dauer larva development initiates, and (2) the specialized differentiation of hypodermal cells during dauer larva morphogenesis. Epistasis analysis has suggested a model in which lin-4 negatively regulates lin-14, and the resulting temporal decrease in lin-14 activity specifies the stage of dauer larva initiation. Our results further suggest that dauer larva morphogenesis by hypodermal cells requires that lin-28 acts to inhibit lin-29 during early larval stages.