Antagonistic Smad transcription factors control the dauer/non-dauer switch in C. elegans.
The C. elegans daf-8 gene encodes an R-Smad that is expressed in a subset of head neurons, the intestine, gonadal distal tip cells and the excretory cell. We found that DAF-8, which inhibits the DAF-3 Co-Smad, is associated with DAF-3 and the DAF-14 Smad in vivo and in vitro. Overexpression of daf-8 conferred a dauer-defective phenotype and suppressed constitutive dauer formation in daf-8 and daf-14 mutants. In contrast to mammalian systems described thus far, active DAF-3 drives a feedback regulatory loop that represses transcription of daf-7 (a TGFbeta ligand) and daf-8 by directly binding to their regulatory regions. Hence, DAF-8 and DAF-3 are mutually antagonistic. The feedback repression may reinforce the developmental switch by allowing DAF-3 to freely activate dauer transcription in target tissues, unless sufficiently inhibited by DAF-8 and DAF-14. In the adult, DAF-8 downregulates lag-2 expression in the distal tip cells, thus promoting germ line meiosis. This function does not involve DAF-3, thereby avoiding the feedback loop that functions in the dauer switch.
Park
Donha
D
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T1Z4, Canada.
Estevez
Annette
A
Riddle
Donald L
DL
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D025461:Feedback, Physiological; D053263:Gene Regulatory Networks; D009154:Mutation; D010641:Phenotype; D051785:Smad Proteins / Q000235:genetics* / Q000502:physiology; D051896:Smad Proteins, Receptor-Regulated / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; C403466:DAF-14 protein, C elegans; C108738:DAF-3 protein, C elegans; C102095:DAF-7 protein, C elegans; C548061:DAF-8 protein, C elegans; D051785:Smad Proteins; D051896:Smad Proteins, Receptor-Regulated; D014157:Transcription Factors; D016212:Transforming Growth Factor beta