daf-12 regulates developmental age and the dauer alternative in Caenorhabditis elegans.

From egg through adult, C. elegans has six life stages including an option for dauer formation and diapause at larval stage L3 in adverse environments. Somatic cells throughout the organism make consistent choices and advance in unison, suggesting a mechanism of coordinate regulation at these stage transitions. Earlier studies showed that daf-12, which encodes a nuclear receptor (W. Yeh, 1991, Doctoral Thesis. University of Missouri-Columbia), regulates dauer formation; epistasis experiments placed daf-12 near the end of the dauer signaling pathway. Here we describe novel daf-12 alleles that reveal a general role in advancing L3 stage programs. In these mutants, somatic cells repeat L2-specific cellular programs of division and migration at the L3 stage; epistasis experiments place daf-12 between lin-14 and lin-28 within the heterochronic pathway. We propose daf-12 and other heterochronic genes provide cellular memories of chronological stage for selecting stage-appropriate developmental programs. Endocrine factors could coordinate these stage transitions and specify developmental alternatives.