Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni
- University of Texas Southwestern Medical Center, United States
- James Cook University, Australia
- Wellcome Trust Sanger Institute, United Kingdom
Abstract
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.
Data availability
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Characterising_Schistosoma_mansoni_stem_cell_populationsERS1987962, ERS1987961, ERS1987958, ERS1987958, ERS1987957, ERS1987948, ERS1987946, ERS1987945, ERS1987942.
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Transcriptional Profiling of Schistosoma mansoni zfp-1-1(RNAi) parasitesPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE106693).
Article and author information
Author details
Funding
National Institutes of Health (R01AI121037)
- James J Collins
Wellcome (107475/Z/15/Z)
- Matthew Berriman
- James J Collins
National Institutes of Health (R01GM094575)
- Nick V Grishin
Welch Foundation (I1505)
- Nick V Grishin
National Health and Medical Research Council
- Alex Loukas
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: In adherence to the Animal Welfare Act and the Public Health Service Policy on Humane Care and Use of Laboratory Animals, all experiments with and care of vertebrate animals were performed in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the UT Southwestern Medical Center (protocol approval number APN 2014-0072).
Copyright
© 2018, Wendt et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Flatworm-specific transcriptional regulators promote the specification of tegumental progenitors in Schistosoma mansoni
eLife 7:e33221.
https://doi.org/10.7554/eLife.33221
Further reading
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- Developmental Biology
The formation of the mammalian brain requires regionalization and morphogenesis of the cranial neural plate, which transforms from an epithelial sheet into a closed tube that provides the structural foundation for neural patterning and circuit formation. Sonic hedgehog (SHH) signaling is important for cranial neural plate patterning and closure, but the transcriptional changes that give rise to the spatially regulated cell fates and behaviors that build the cranial neural tube have not been systematically analyzed. Here, we used single-cell RNA sequencing to generate an atlas of gene expression at six consecutive stages of cranial neural tube closure in the mouse embryo. Ordering transcriptional profiles relative to the major axes of gene expression predicted spatially regulated expression of 870 genes along the anterior-posterior and mediolateral axes of the cranial neural plate and reproduced known expression patterns with over 85% accuracy. Single-cell RNA sequencing of embryos with activated SHH signaling revealed distinct SHH-regulated transcriptional programs in the developing forebrain, midbrain, and hindbrain, suggesting a complex interplay between anterior-posterior and mediolateral patterning systems. These results define a spatiotemporally resolved map of gene expression during cranial neural tube closure and provide a resource for investigating the transcriptional events that drive early mammalian brain development.
