Abstract
Backgroundpha-4 encodes a forkhead box (FOX) A transcription factor serving as the C. elegans pharynx organ identity factor during embryogenesis. Using Serial Analysis of Gene Expression (SAGE), comparison of gene expression profiles between growing stages animals and long-lived, developmentally diapaused dauer larvae revealed that pha-4 transcription is increased in the dauer stage.ResultsKnocking 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.ConclusionAnalysis 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.
Highlights
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]
The vulval transcription of lag-2, which encodes a ligand for the LIN-12/Notch lateral signaling pathway, is inhibited by pha-4 double stranded RNAi-mediated interference (RNAi), indicating that LAG-2 functions downstream of PHA-4 in vulva development
PHA-4 is required for dauer recovery, gonad and vulva development Serial Analysis of Gene Expression (SAGE) revealed that pha-4 transcription is elevated in dauer larvae [22], suggesting that, in addition to pharyngeal organogenesis, PHA-4 may function in dauer formation or recovery
Summary
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]. Genes involved in dauer formation are called daf genes. Dauer-constitutive (Daf-c) mutants form dauer larvae in an environment with abundant food, whereas dauerdefective (Daf-d) mutants fail to enter the dauer stage when they are starved or overcrowded. Three functionally overlapping pathways, including TGF-β, insulin/IGF-1, and cyclic GMP signaling pathways, are involved in responding to environmental cues [6]. DAF-7, a member of the TGF-β superfamily of protein growth factors, signals through downstream receptor kinases, SMAD transcription factors and the DAF-12 nuclear hormone receptor to inhibit dauer formation and promote reproductive development [7,8,9,10,11,12]. The daf-2 gene encodes an IGF-1 receptor, which functions through downstream kinases to phosphorylate the DAF-16/FOXO transcription factor [13,14,15,16,17], and to influence the biosynthesis of ligands for DAF-12 [18,19,20,21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
