A chemical genetics approach reveals H,K-ATPase-mediated membrane voltage is required for planarian head regeneration

Chem Biol. 2011 Jan 28;18(1):77-89. doi: 10.1016/j.chembiol.2010.11.012.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Calcium Signaling / drug effects
  • Cell Polarity / drug effects
  • Enzyme Inhibitors / pharmacology
  • H(+)-K(+)-Exchanging ATPase / genetics*
  • H(+)-K(+)-Exchanging ATPase / metabolism*
  • Head / physiology*
  • Membrane Potentials / drug effects*
  • Planarians / cytology
  • Planarians / drug effects
  • Planarians / enzymology*
  • Planarians / physiology*
  • Proton Pump Inhibitors
  • Regeneration / drug effects
  • Regeneration / physiology*
  • Tail / drug effects
  • Tail / physiology


  • Enzyme Inhibitors
  • Proton Pump Inhibitors
  • H(+)-K(+)-Exchanging ATPase