Fig 1. Transcriptional changes pertaining to dauer signalling genes, and quantification of dafachronic acids in Haemonchus contortus during developmental transition.

(A) Model of the cyclic guanosine monophosphate (cGMP) (red), DAF-7-related transforming growth factor-β (TGF-β) (orange), DAF-2-related insulin-like growth factor 1 (IGF-1) (green) and steroid hormone signalling (blue) pathways proposed for H. contortus [34]. This model is predicted to play a role in integrating environmental signals to control the biosynthesis of one or more dafachronic acids (DAs), which activate the nuclear hormone receptor DAF-12. The DA-DAF-12 module might serve as a checkpoint for developmental decisions and associate with nutrient metabolism in parasitic nematodes [8,14,17,34]. (B) Transcriptional profiles (Z-score normalised, mapped reads per million) of 61 gene homologues involved in the cGMP (red), TGF-β (orange), IGF-1 (green) and steroid hormone (blue) signalling pathways are displayed for the developmental transition from the dauer-like third larval stage (L3), via exsheathed L3 (xL3), to the parasitic fourth larval stage (L4) of H. contortus in vitro. (C) Using (25S)-Δ4-DA (calculated mass: 413.3061, retention time: 4.0 min) and (25S)-Δ7-DA (calculated mass: 413.3061; retention time: 4.2 min) as references (blue peaks), endogenous Δ7-DA (retention time: 4.2 min; red peak) was detected in H. contortus with mass error estimated at 0.5 part per million (ppm). (D) The relative abundance of endogenous Δ7-DA following larval exsheathment and in the ensuing larval development in vitro is indicated.