During development, networks of regulatory genes control precisely timed sequences of developmental events. In C. elegans, heterochronic genes, which encode several transcription factors and microRNAs (miRNAs) that regulate the expression of these transcription factors, control stage-specific cell-fate decisions. Under adverse conditions, however, second larval stage (L2) worms enter a quiescent state called dauer. Intriguingly, when conditions improve, dauer larvae complete development normally. Here (), Xantha Karp and Victor Ambros investigate how cell-fate progression is reset after dauer. Progression from L2 to L3 requires downregulation of the transcription factor Hunchback-like-1 (HBL-1), and, during continuous development, HBL-1 downregulation relies mainly on three let-7 family miRNAs. However, after dauer, the researchers report, lin-4 miRNA and an altered set of let-7 family miRNAs downregulate HBL-1. This shift in the programming of HBL-1 downregulation, they propose, involves the enhancement of lin-4 and let-7 miRNA activity by miRNA-induced silencing complex (miRISC) modulators. The employment of alternative genetic regulatory pathways can, therefore, ensure the robust progression of cell-fate specification after temporary developmental quiescence.
