Figure 7.

HSF-2 antagonizes HSF-1 to influence development. A, The structure of hsf2. 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 hsf2. B, tm4607 promotes dauer development in daf11(−) mutants. Thus, HSF-2 acts downstream of, or in parallel to, DAF-11 to influence dauer formation, and antagonizes HSF1 in this function. hsf2(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 hsf2 enhances dauer development in unc3(−) mutant (p<0.001), but not in unc31(−) 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 hsf2 in this signaling network is uncertain. hsf2 may act upstream of either unc31 or daf11. 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.