C. elegans STAT cooperates with DAF-7/TGF-beta signaling to repress dauer formation.
The DAF-7/TGF-beta pathway in C. elegans interprets environmental signals relayed through amphid neurons and actively inhibits dauer formation during reproductive developmental growth . In metazoans, the STAT pathway interprets external stimuli through regulated tyrosine phosphorylation, nuclear translocation, and gene expression , but its importance for developmental commitment, particularly in conjunction with TGF-beta, remains largely unknown. Here, we report that the nematode STAT ortholog STA-1 accumulated in the nuclei of five head neuron pairs, three of which are amphid neurons involved in dauer formation . Moreover, sta-1 mutants showed a synthetic dauer phenotype with selected TGF-beta mutations. sta-1 deficiency was complemented by reconstitution with wild-type protein, but not with a tyrosine mutant. Canonical TGF-beta signaling involves the DAF-7/TGF-beta ligand activating the DAF-1/DAF-4 receptor pair to regulate the DAF-8/DAF-14 Smads . Interestingly, STA-1 functioned in the absence of DAF-7, DAF-4, and DAF-14, but it required DAF-1 and DAF-8. Additionally, STA-1 expression was induced by TGF-beta in a DAF-3-dependent manner, demonstrating a homeostatic negative feedback loop. These results highlight a role for activated STAT proteins in repression of dauer formation. They also raise the possibility of an unexpected function for DAF-1 and DAF-8 that is independent of their normal upstream activator, DAF-7.
Wang
Yaming
Y
Department of Pathology, Department of Microbiology, NYU Cancer Institute, New York University School of Medicine, 550 1st Avenue, New York, New York 10016, USA.
Levy
David E
DE
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004252:DNA Mutational Analysis; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D009475:Neurons, Afferent / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D012097:Repressor Proteins; C508385:STA-1 protein, C elegans; D050791:STAT Transcription Factors; D015534:Trans-Activators; D016212:Transforming Growth Factor beta