The Schistosoma mansoni nuclear receptor FTZ-F1 maintains esophageal gland function via transcriptional regulation of meg-8.3

Schistosomes infect over 200 million of the world's poorest people, but unfortunately treatment relies on a single drug. Nuclear hormone receptors are ligand-activated transcription factors that regulate diverse processes in metazoans, yet few have been functionally characterized in schistosomes. During a systematic analysis of nuclear receptor function, we found that an FTZ-F1-like receptor was essential for parasite survival. Using a combination of transcriptional profiling and chromatin immunoprecipitation (ChIP), we discovered that the micro-exon gene meg-8.3 is a transcriptional target of SmFTZ-F1. We found that both Smftz-f1 and meg-8.3 are required for esophageal gland maintenance as well as integrity of the worm's head. Together, these studies define a new role for micro-exon gene function in the parasite and suggest that factors associated with the esophageal gland could represent viable therapeutic targets. Author summarySchistosomes kill an estimated 250,000 people every year and cause severe morbidity in millions more. Therefore, it is critical we continue to understand fundamental processes in the parasite so new therapies can be developed. Here, we identify a transcriptional regulator protein SmFTZ-F1 that is critical for parasite survival. We find that this protein controls the levels of a schistosome-specific gene (meg-8.3) and that meg-8.3 is critical for the maintenance of the worm's esophageal gland. Loss of \ either meg-8.3 or Smftz-f1 leads to degeneration of the parasites' head tissues. These studies suggest that molecules associated with esophageal gland function could represent therapeutic targets.