Abstract
Based on metabolic and morphological similarities between infective third-stage larvae of parasitic nematodes and dauer larvae of Caenorhabditis elegans, it is hypothesized that similar genetic mechanisms control the development of these forms. In the parasite Strongyloides stercoralis, FKTF-1 is an ortholog of DAF-16, a forkhead transcription factor that regulates dauer larval development in C. elegans. Using transgenesis, we investigated the role of FKTF-1 in S. stercoralis' infective larval development. In first-stage larvae, GFP-tagged recombinant FKTF-1b localizes to the pharynx and hypodermis, tissues remodeled in infective larvae. Activating and inactivating mutations at predicted AKT phosphorylation sites on FKTF-1b give constitutive cytoplasmic and nuclear localization of the protein, respectively, indicating that its post-translational regulation is similar to other FOXO-class transcription factors. Mutant constructs designed to interfere with endogenous FKTF-1b function altered the intestinal and pharyngeal development of the larvae and resulted in some transgenic larvae failing to arrest in the infective stage. Our findings indicate that FKTF-1b is required for proper morphogenesis of S. stercoralis infective larvae and support the overall hypothesis of similar regulation of dauer development in C. elegans and the formation of infective larvae in parasitic nematodes.
Highlights
Parasitism among nematodes appears to have arisen multiple times throughout evolution [1]
We identified S. stercoralis’ FKTF-1 as an ortholog of DAF-16, a forkhead transcription factor controlling dauer larval development in C. elegans
Transgenes were introduced into S. stercoralis to investigate the possibility that FKTF-1 regulates development of its infective larvae
Summary
Parasitism among nematodes appears to have arisen multiple times throughout evolution [1]. First-stage larval progeny of parasitic S. stercoralis females typically develop into free-living adults unless triggered by genetic, environmental or host-associated conditions to develop directly into infective third-stage larvae (L3i) [10]. A transgene construct designed to express FKTF-1b (isoform b) partially restored DAF-16 function to C. elegans daf-2;daf-16 double mutants [12] rescuing the dauer development phenotype. These data indicate that fktf-1b encodes a working forkhead transcription factor that can function in insulin-like signaling to regulate L3 development in C. elegans. We examined first-stage larval progeny of these female worms for anatomical and intra-cellular localization of GFP-linked proteins and for phenotypes associated with expression of transgenes encoding mutant forms of FKTF-1b.
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