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.

Atypical life cycle does not lead to inbreeding or selfing in parasites despite clonemate accumulation in intermediate hosts.

Many parasites utilize asexual and sexual reproduction and multiple hosts to complete their life cycles. How these taxa avoid inbreeding is an essential question for understanding parasite evolution and ecology. Aquatic trematodes that require multiple host species may benefit from diverse genetic parasite assemblages accumulating within second intermediate hosts prior to sexual reproduction in definitive hosts. However, Cotylurus species are able to utilize the same snail species as first and second intermediate hosts, potentially resulting in the accumulation of genetically identical clones (clonemates) prior to sexual reproduction. In this study, we developed and analysed novel microsatellite loci to determine if clones are accumulating within snail hosts prior to ingestion by bird hosts and the effects this could have on parasite inbreeding. Contrary to previous studies of aquatic trematodes, significantly large numbers of clonemates were present within snails, but full-sibs were not. Genetic structure was present over a relatively small geographical scale despite the use of vagile definitive hosts. Phylogenetic analysis identified the Cotylurus sp. clones as belonging to a single species. Despite the presence of clones within snails, mating between clones/selfing was not common and heterozygosity is maintained within individuals. Potential issues with clones mating may be mitigated by the presence of snails with numerous clones, the consumption of many snails by bird hosts and parasite clone recognition/avoidance. Use of the same host species for multiple life stages may have advantages when parasites are able to avoid inbreeding and the required hosts are common.

DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors.

Fertility across metazoa requires the germline-specific DAZ family of RNA-binding proteins. Here we examine whether DAZL directly regulates progenitor spermatogonia using a conditional genetic mouse model and in vivo biochemical approaches combined with chemical synchronization of spermatogenesis. We find that the absence of Dazl impairs both expansion and differentiation of the spermatogonial progenitor population. In undifferentiated spermatogonia, DAZL binds the 3' UTRs of ~2,500 protein-coding genes. Some targets are known regulators of spermatogonial proliferation and differentiation while others are broadly expressed, dosage-sensitive factors that control transcription and RNA metabolism. DAZL binds 3' UTR sites conserved across vertebrates at a UGUU(U/A) motif. By assessing ribosome occupancy in undifferentiated spermatogonia, we find that DAZL increases translation of its targets. In total, DAZL orchestrates a broad translational program that amplifies protein levels of key spermatogonial and gene regulatory factors to promote the expansion and differentiation of progenitor spermatogonia.