A chemical genetics approach reveals H,K-ATPase-mediated membrane voltage is required for planarian head regeneration |
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Authors: | Beane Wendy S Morokuma Junji Adams Dany S Levin Michael |
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Institution: | Biology Department and Tufts Center for Regenerative and Developmental Biology, Tufts University, Medford, MA 02155-4243, USA. |
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Abstract: | Biophysical signaling is required for both embryonic polarity and regenerative outgrowth. Exploiting endogenous ion transport for regenerative therapies will require direct regulation of membrane voltage. Here, we develop a pharmacological method to target ion transporters, uncovering a role for membrane voltage as a key regulator of anterior polarity in regenerating planaria. Utilizing the highly specific inhibitor, SCH-28080, our data reveal that H(+),K(+)-ATPase-mediated membrane depolarization is essential for anterior gene expression and brain induction. H(+),K(+)-ATPase-independent manipulation of membrane potential with ivermectin confirms that depolarization drives head formation, even at?posterior-facing wounds. Using this chemical genetics approach, we demonstrate that membrane voltage controls head-versus-tail identity during planarian regeneration. Our data suggest well-characterized drugs (already approved for human use) might be exploited to control adult stem cell-driven pattern formation during the regeneration of complex structures. |
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