Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni

Schistosomes infect more than 200 million people. These parasitic flatworms rely on a syncytial outer coat called the tegument to survive within the vasculature of their host. Although the tegument is pivotal for their survival, little is known about maintenance of this tissue during the decades schistosomes survive in the bloodstream. Here, we demonstrate that the tegument relies on stem cells (neoblasts) to specify fusogenic progenitors that replace tegumental cells lost to turnover. Molecular characterization of neoblasts and tegumental progenitors led to the discovery of two flatworm-specific zinc finger proteins that are essential for tegumental cell specification. These proteins are homologous to a protein essential for neoblast-driven epidermal maintenance in free-living flatworms. Therefore, we speculate that related parasites (i.e., tapeworms and flukes) employ similar strategies to control tegumental maintenance. Since parasitic flatworms infect every vertebrate species, understanding neoblast-driven tegumental maintenance could identify broad-spectrum therapeutics to fight diseases caused by these parasites.
eLife digest Schistosomiasis is a devastating disease that infects more than 200 million people and kills 200 thousand people every year. The disease is caused by parasitic flatworms known as schistosomes. These worms can live in the bloodstream for decades, even if the host has a healthy immune system. This ability to evade the immune system is thought to be partly due to the worm’s special ‘skin’, a tissue referred to as the tegument that all parasitic flatworms have. The tegument is a massive cell that covers the entire surface of the worm, and is thought to be an adaptation that enabled flatworms to become parasites. Despite the important role that the tegument appears to play in the biology of parasitic flatworms, very little is actually known about how this tissue is made and maintained. The tegument likely experiences a great deal of damage because it serves as the interface between the parasite and the host. Can the parasite repair the tissue as it becomes damaged? If the parasite relies upon this renewal, then preventing schistosomes from repairing their tegument could be a new way to treat schistosomiasis. Wendt et al. developed a new technique to fluorescently label a schistosome’s tegument. This revealed that the parasite does continuously repair and replace its tegument. To better understand this process, Wendt et al. identified genes that were active in the cells responsible for making the tegument. Two of these genes appear to regulate tegument production, and these genes can be found in both parasitic and non-parasitic flatworms. Further studies of these genes could shed light specifically onto how parasitism arose in flatworms. In addition, a better understanding of how the tegument develops and functions could identify new drug targets that could be used against the many diseases caused by parasitic flatworms.