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

Chem Biol 2011 Jan;18(1):77-89

Biology Department and Tufts Center for Regenerative and Developmental Biology, Tufts University, Medford, MA 02155-4243, USA.

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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Source
https://linkinghub.elsevier.com/retrieve/pii/S10745521100044
Publisher Site
http://dx.doi.org/10.1016/j.chembiol.2010.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278711PMC
January 2011

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