A daf-7-related TGF-β ligand (Hc-tgh-2) shows important regulations on the development of Haemonchus contortus

Abstract

Background: In most multicellular organisms, the transforming growth factor-β (TGF-β) signalling pathway is involved in regulating the growth and stem cell differentiation. Previous studies have demonstrated the importance of three key molecules in this pathway in the parasitic nematode Haemonchus contortus, including one TGF-β type I receptor (Hc-tgfbr1), one TGF-β type II receptor (Hc-tgfbr2), and one co-Smad (Hc-daf-3), which regulated the developmental transition from the free-living to the parasitic stages of this parasite. However, almost nothing is known about the function of the TGF-β ligand (Hc-tgh-2) of H. contortus. Methods: Here, the temporal transcription profiles of Hc-tgh-2 at eight different developmental stages and spatial expression patterns of Hc-TGH-2 in adult female and male worms of H. contortus have been examined by real-time PCR and immunohistochemistry, respectively. In addition, RNA interference (RNAi) by soaking was employed to assess the importance of Hc-tgh-2 in the development from exsheathed third-stage larvae (xL3s) to fourth-stage larvae (L4s) in H. contortus. Results: Hc-tgh-2 was continuously transcribed in all eight developmental stages of H. contortus studied with the highest level in the infective third-stage larvae (iL3) and Hc-TGH-2 was located in the muscle of the body wall, intestine, ovary of adult females and testes of adult males. Silencing Hc-tgh-2 by the specific double-stranded RNA (dsRNA), decreased the transcript level of Hc-tgh-2 and resulted in fewer xL3s developing to L4s in vitro. Conclusions: These results suggested that the TGF-β ligand, Hc-TGH-2, could play important roles in the developmental transition from the free-living (L3s) to the parasitic stage (L4s). Furthermore, it may also take part in the processes such as digestion, absorption, host immune response and reproductive development in H. contortus adults.

A novel BR-SMAD is required for larval development in barber’s pole worm Haemonchus contortus

“…3E). These results suggest a role of HcSMA2 in differentiation of infective xL3 to L4 larvae, which is consistent with the function of the known members of the TGF-β and Insulin signaling [8][9][10][11][12]23]. In C. elegans, CeSMA2 regulates the body size [24], morphogenesis of the male worm's tail tip [25], as well as reproductive aging [21,26].…”

“…In Haemonchus contortus, previous work demonstrating the important roles of DAF7 signaling during larval development of this economically important nematode parasite has focused on TGF-β ligand [8], TGF-β type I receptor [9], TGF-β type II receptor [10]), TGF-β-regulated R-SMAD [11] and Co-SMAD [12]. Little is known about BMP (DBL1) signaling in this parasite, however.…”

Evolution and Diversity of TGF-β Pathways are Linked with Novel Developmental and Behavioral Traits

“…These possibilities may be clarified further by the creation of a full Ppa-daf-7 null mutant consisting of mutations in all seven Ppa-daf-7 paralogues. Importantly, due to the similarities between the dauer stage in free-living nematodes and the infective larvae in parasitic nematode species, the presumed association of TGF-β signaling with dauer formation has formed the basis for substantial parasitic research as a potential target to understand their infectivity ( McSorley et al 2009 ; Ogawa et al 2009 ; Crook et al 2010 ; Ma et al 2019 ; Yang et al 2019 ; He et al 2020 ). Therefore, functional studies in other nematode species will be essential to distinguish between these possibilities, and further inform research on parasitic nematodes.…”

“…This is due to the similarities between the dauer stage in free-living nematodes and the infective larvae of many parasitic nematode species ( Viney et al 2005 ; Gilabert et al 2016 ). As such, several TGF-β family members have been identified in parasitic nematodes, although functional studies are problematic due to the complex life cycles found in these organisms ( McSorley et al 2009 ; Ogawa et al 2009 ; Crook et al 2010 ; Ma et al 2019 ; Yang et al 2019 ; He et al 2020 ). Interestingly, a recent study in P. pacificus demonstrated that the Ppa-daf-7 pathway is necessary for bacterial induced gut–brain communication, which in turn enhanced numerous developmental phenotypes ( Lo et al 2022 ).…”

Importance of TGFβ in Cancer and Nematode Infection and Their Interaction—Opinion

“…The Hc-tgh-2 gene is expressed by all developmental stages, with iL3 expressing the most. Hc-TGH-2 seems to play an important role in the transition from the free-living to parasitic stage, as well as in digestion, absorption, and reproductive development, based on the localisation of the ligand in parasite body [ 61 ].…”