activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis
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journal.pgen.1009466.pdf
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Published version
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Author(s) • • •
Cloutier, Jennifer K
McMann, Conor L
Oderberg, Isaac M
Reddien, Peter W
Date Issued
2021
Journal
PLoS Genetics
Publisher
Public Library of Science (PLoS)
Version
Final published version
Abstract
Planarians are flatworms and can perform whole-body regeneration. This ability involves a mechanism to distinguish between anterior-facing wounds that require head regeneration and posterior-facing wounds that require tail regeneration. How this head-tail regeneration polarity decision is made is studied to identify principles underlying tissue-identity specification in regeneration. We report that inhibition ofactivin-2, which encodes an Activin-like signaling ligand, resulted in the regeneration of ectopic posterior-facing heads following amputation. During tissue turnover in uninjured planarians, positional information is constitutively expressed in muscle to maintain proper patterning. Positional information includes Wnts expressed in the posterior and Wnt antagonists expressed in the anterior. Upon amputation, several wound-induced genes promote re-establishment of positional information. The head-versus-tail regeneration decision involves preferential wound induction of the Wnt antagonistnotumat anterior-facing over posterior-facing wounds. Asymmetric activation ofnotumrepresents the earliest known molecular distinction between head and tail regeneration, yet how it occurs is unknown.activin-2RNAi animals displayed symmetric wound-induced activation ofnotumat anterior- and posterior-facing wounds, providing a molecular explanation for their ectopic posterior-head phenotype.activin-2RNAi animals also displayed anterior-posterior (AP) axis splitting, with two heads appearing in anterior blastemas, and various combinations of heads and tails appearing in posterior blastemas. This was associated with ectopic nucleation of anterior poles, which are head-tip muscle cells that facilitate AP and medial-lateral (ML) pattern at posterior-facing wounds. These findings reveal a role for Activin signaling in determining the outcome of AP-axis-patterning events that are specific to regeneration.
MIT Department
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1371/journal.pgen.1009466