Format

Send to

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

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

Author information

1
Biology Department and Tufts Center for Regenerative and Developmental Biology, Tufts University, Medford, MA 02155-4243, USA.

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.

PMID:
21276941
PMCID:
PMC3278711
DOI:
10.1016/j.chembiol.2010.11.012
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center