Function of the PHA-4/FOXA transcription factor during C. elegans post-embryonic development

Knocking down pha-4 expression by RNAi during post-embryonic development showed that PHA-4 is essential for dauer recovery, gonad and vulva development. daf-16, which encodes a FOXO transcription factor regulated by insulin/IGF-1 signaling, shows overlapping expression patterns and a loss-of-function post-embryonic phenotype similar to that of pha-4 during dauer recovery. pha-4 RNAi and daf-16 mutations have additive effects on dauer recovery, suggesting these two regulators may function in parallel pathways. Gene expression studies using RT-PCR and GFP reporters showed that pha-4 transcription is elevated under starvation, and a conserved forkhead transcription factor binding site in the second intron of pha-4 is important for the neuronal expression. The vulval transcription of lag-2, which encodes a ligand for the LIN-12/Notch lateral signaling pathway, is inhibited by pha-4 RNAi, indicating that LAG-2 functions downstream of PHA-4 in vulva development.Analysis of PHA-4 during post-embryonic development revealed previously unsuspected functions for this important transcriptional regulator in dauer recovery, and may help explain the network of transcriptional control integrating organogenesis with the decision between growth and developmental arrest at the dauer entry and exit stages.At the second larval molt, C. elegans may arrest development at the dauer stage in response to starvation and overcrowding, but can resume development to the adult when an environment favoring growth is encountered [1]. Entry into and exit from the dauer stage are determined by environmental cues, such as temperature, food supply and a constitutively released, dauer-inducing pheromone [2-4]. Genes involved in dauer formation are called daf genes. Dauer-constitutive (Daf-c) mutants form dauer larvae in an environment with abundant food, whereas dauer-defective (Daf-d) mutants fail to enter the dauer stage when they are starved or overcrowded. Most Daf-c mutants are temperature-sensitiv