Tapeworms grow at rates rivaling the fastest-growing metazoan tissues. To propagate they shed large parts of their body; to replace these lost tissues they regenerate proglottids (segments) as part of normal homeostasis. Their remarkable growth and regeneration are fueled by adult somatic stem cells that have yet to be characterized molecularly. Using the rat intestinal tapeworm, Hymenolepis diminuta, we find that regenerative potential is regionally limited to the neck, where head-dependent extrinsic signals create a permissive microenvironment for stem cell-driven regeneration. Using transcriptomic analyses and RNA interference, we characterize and functionally validate regulators of tapeworm growth and regeneration. We find no evidence that stem cells are restricted to the regeneration-competent neck. Instead, lethally irradiated tapeworms can be rescued when cells from either regeneration-competent or regeneration-incompetent regions are transplanted into the neck. Together, the head and neck tissues provide extrinsic cues that regulate stem cells, enabling region-specific regeneration in this parasite.
Sequencing data have been deposited in DDB/ENA/Genbank under accession codes GHNR01000000, PRJNA546290, PRJNA546293.
Hymenolepis diminuta transcriptomeBioProject, PRJNA546290.
Region-specific regulation of stem cell-driven regeneration in tapewormsBioProject, PRJNA546293.
Hymenolepis diminuta transcriptome shotgun assemblyNCBI, GHNR01000000.
- Phillip A Newmark
- Phillip A Newmark
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Rodent care was in accordance with protocols approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Wisconsin-Madison (M005573).
- Yukiko M Yamashita, University of Michigan, United States
© 2019, Rozario 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.
Development of tooth shape is regulated by the enamel knot signalling centre, at least in mammals. Fgf signalling regulates differential proliferation between the enamel knot and adjacent dental epithelia during tooth development, leading to formation of the dental cusp. The presence of an enamel knot in non-mammalian vertebrates is debated given differences in signalling. Here, we show the conservation and restriction of fgf3, fgf10, and shh to the sites of future dental cusps in the shark (Scyliorhinus canicula), whilst also highlighting striking differences between the shark and mouse. We reveal shifts in tooth size, shape, and cusp number following small molecule perturbations of canonical Wnt signalling. Resulting tooth phenotypes mirror observed effects in mammals, where canonical Wnt has been implicated as an upstream regulator of enamel knot signalling. In silico modelling of shark dental morphogenesis demonstrates how subtle changes in activatory and inhibitory signals can alter tooth shape, resembling developmental phenotypes and cusp shapes observed following experimental Wnt perturbation. Our results support the functional conservation of an enamel knot-like signalling centre throughout vertebrates and suggest that varied tooth types from sharks to mammals follow a similar developmental bauplan. Lineage-specific differences in signalling are not sufficient in refuting homology of this signalling centre, which is likely older than teeth themselves.
The tooth shape of sharks and mice are regulated by a similar signaling center despite their teeth having very different geometries.