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. 2019 May 24;2(3):e201800255. doi: 10.26508/lsa.201800255

Figure 4. The HIF-1 target NHR-57 inhibits RAS/MAPK signaling under normoxia and hypoxia.

Figure 4.

(A) Knock-down of nhr-57 increases the VI of let-60(n1046gf) in an egl-9(sa307lf) but not in a hif-1(zh111lf) background. ∆VI and ∆%Muv indicate the changes in VI and percentage of animals with VI > 3 after nhr-57 RNAi compared with empty vector–treated control animals. (B) Deletion of the nhr-57(tm4533lf) allele increases the VI of let-60(n1046gf) single and let-60(n1046gf); egl-9(sa307lf) double mutants but has no effect in a let-60(n1046gf); hif-1(zh111lf) background. ∆VI and ∆%Muv indicate the changes in VI and the percentage of animals with VI > 3 compared with nhr-57(+) control siblings. (C) Hypoxic treatment decreases the VI in the hif-1(ia04lf), hif-1(zh111lf), and egl-9(sa307lf) hif-1(ia04lf) but not the nhr-57(tm4533lf) background. ∆VI and ∆%Muv indicate the changes in VI and percentage of animals with VI > 3 raised in hypoxia compared with normoxia. Error bars indicate 95% confidence intervals, and P-values, indicated with ***P < 0.001 and **P < 0.01, were derived by bootstrapping 1,000 samples. The numbers of animals scored are indicated in brackets. (D) NHR-57::GFP expression pattern in the wild-type (left panels) and egl-9(sa307lf) (right panels) background in late-L2/early-L3 larvae at the Pn.p stage (top panels), in mid L3 larvae (Pn.px stage) after induction (middle panels), and at the end of vulval differentiation (bottom panels). Arrowheads and solid lines point at the nuclei of the induced or uninduced VPCs and their descendants, respectively. The scale bar represents 5 μm. (E) Schematic representation of the NHR-57::GFP pattern during vulval development in the wild-type (left) and in an egl-9(sa307lf) background (right).