Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni
George R Wendt,
Julie NR Collins,
Jimin Pei,
Mark S Pearson,
Hayley M Bennett,
Alex Loukas,
Matthew Berriman,
Nick V Grishin,
James J Collins III
Affiliations
George R Wendt
Department of Pharmacology, UT Southwestern Medical Center, Dallas, Texas
Julie NR Collins
Department of Pharmacology, UT Southwestern Medical Center, Dallas, Texas
Jimin Pei
Department of Biophysics, UT Southwestern Medical Center, Dallas, Texas; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, Texas
Center for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia
Hayley M Bennett
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
Alex Loukas
Center for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
Nick V Grishin
Department of Biophysics, UT Southwestern Medical Center, Dallas, Texas; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, Texas
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.
