Figure 7

HSF - 2 antagonizes HSF - 1 to influence development. A, The structure of hsf 2. Blue boxes and interconnecting lines represent exonic and intronic sequences, respectively. The red line represents the extent of tm4607, which is a deletion removing upstream regulatory sequences and the first exon of hsf 2. B, tm4607 promotes dauer development in daf 11(−) mutants. Thus, HSF-2 acts downstream of, or in parallel to, DAF-11 to influence dauer formation, and antagonizes HSF1 in this function. hsf 2(tm6407) single mutant animals are superficially wild-type; they exhibit neither a dauer formation constitutive phenotype at 25-27°C nor a long-lived phenotype. p<0.0001, Student’s t-test. C, Inactivation of hsf 2 enhances dauer development in unc 3(−) mutant (p<0.001), but not in unc 31(−) mutant background (p=0.46), Student’s t-test. D, Our current model showing how HSF-1 interconnects insulin/IGF-1, cGMP and TGF-β signaling to control development and longevity. Arrows indicate activations, bars represents inhibitory regulations. Downstream of HSF-1, regulatory inputs affecting longevity are indicated by green coloring, and regulatory inputs on development are indicated by black arrows and bars. IGF-1: insulin/IGF-1 signaling, TGF-β: TGF-β signaling, cGMP: cGMP signaling. Grey arrows and the question mark indicate that the epistatic position of hsf 2 in this signaling network is uncertain. hsf 2 may act upstream of either unc 31 or daf 11. Regulatory inputs shown here do not necessarily represent direct interactions. For example, DAF-3 modulates DAF-2 activity (the green dotted bar) through its regulation of the INS-7 (agonist) and INS-18 (antagonist) insulin-like peptides encoding genes [5, 22]. In panels B and C, bars represent S.E.M.