title: A chemical genetics approach reveals H,K-ATPase-mediated membrane voltage is required for planarian head regeneration.
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.
authors.affiliation: Biology Department and Tufts Center for Regenerative and Developmental Biology, Tufts University, Medford, MA 02155-4243, USA.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Beane
authors.forename: Junji
authors.initials: J
authors.lastname: Morokuma
authors.forename: Dany S
authors.initials: DS
authors.lastname: Adams
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism*; D006257:Head / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects*; D010932:Planarians / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D054328:Proton Pump Inhibitors; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013623:Tail / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D017506:H(+)-K(+)-Exchanging ATPase