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

  • Chen, Di1, 2, 3
  • Riddle, Donald L1, 2
  • 1 University of Missouri, Division of Biological Sciences, Columbia, MO, 65211, USA , Columbia
  • 2 University of British Columbia, Michael Smith Laboratories, Vancouver, BC, V6T 1Z4, Canada , Vancouver
  • 3 Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA, 94945, USA , Novato
Published Article
BMC Developmental Biology
Springer (Biomed Central Ltd.)
Publication Date
Feb 29, 2008
DOI: 10.1186/1471-213X-8-26
Springer Nature


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.

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