Nuclear Receptor FTZ-F1 and Downstream Target Gene Meg-8.3 Control Esophageal Gland Function in S. Mansoni

Schistosomes infect over 200 million of the world's poorest people, yet treatment relies on a single drug. Nuclear hormone receptors are ligand-activated transcription factors that regulate diverse processes in metazoans and are known drug targets in humans. However, few nuclear hormone receptors have been characterized functionally in the parasite. During a systematic analysis of nuclear receptor function, we have identified one receptor, an FTZ-F1-like receptor that is essential for parasite survival. Using a combination of transcriptional profiling and chromatin immunoprecipitation we identify the micro-exon gene, meg-8.3, a direct transcriptional target of FTZ-F1 which is also essential for parasite survival. We find that RNAi of either ftz-f1 or meg-8.3 are required for esophageal gland function and maintenance of tissue in the worm head. Together, our data suggest that FTZ-F1 regulates meg-8.3 transcription, and this regulation is essential to esophageal gland function. These data suggest that drugs that alter the activities of proteins in the parasite's esophageal gland could have therapeutic potential.