QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 28 February 2007
doi: 10.1242/dev.02812

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: dev.02812v1 134/7/1323    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Adams, D. S. Articles by Levin, M. Search for Related Content PubMed PubMed Citation Articles by Adams, D. S. Articles by Levin, M. Social Bookmarking                         What's this?

H⁺ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration

Center for Regenerative and Developmental Biology, Forsyth Institute, and Developmental Biology Department, Harvard School of Dental Medicine, 140 The Fenway, Boston, MA 02115, USA.

^* Author for correspondence (e-mail: mlevin{at}forsyth.org)

Accepted 17 January 2007

In many systems, ion flows and long-term endogenous voltage gradients regulate patterning events, but molecular details remain mysterious. To establish a mechanistic link between biophysical events and regeneration, we investigated the role of ion transport during Xenopus tail regeneration. We show that activity of the V-ATPase H⁺ pump is required for regeneration but not wound healing or tail development. The V-ATPase is specifically upregulated in existing wound cells by 6 hours post-amputation. Pharmacological or molecular genetic loss of V-ATPase function and the consequent strong depolarization abrogates regeneration without inducing apoptosis. Uncut tails are normally mostly polarized, with discrete populations of depolarized cells throughout. After amputation, the normal regeneration bud is depolarized, but by 24 hours post-amputation becomes rapidly repolarized by the activity of the V-ATPase, and an island of depolarized cells appears just anterior to the regeneration bud. Tail buds in a non-regenerative `refractory' state instead remain highly depolarized relative to uncut or regenerating tails. Depolarization caused by V-ATPase loss-of-function results in a drastic reduction of cell proliferation in the bud, a profound mispatterning of neural components, and a failure to regenerate. Crucially, induction of H⁺ flux is sufficient to rescue axonal patterning and tail outgrowth in otherwise non-regenerative conditions. These data provide the first detailed mechanistic synthesis of bioelectrical, molecular and cell-biological events underlying the regeneration of a complex vertebrate structure that includes spinal cord, and suggest a model of the biophysical and molecular steps underlying tail regeneration. Control of H⁺ flows represents a very important new modality that, together with traditional biochemical approaches, may eventually allow augmentation of regeneration for therapeutic applications.

Key words: Regeneration, Xenopus, Tail, Ion pump, H⁺ flow

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in Development:

Turning up the voltage on regeneration

Development 2007 134: e703. [Full Text]  

This article has been cited by other articles:

				C. D. McCaig, B. Song, and A. M. Rajnicek Electrical dimensions in cell science J. Cell Sci., December 1, 2009; 122(23): 4267 - 4276. [Abstract] [Full Text] [PDF]

				T. Fukazawa, Y. Naora, T. Kunieda, and T. Kubo Suppression of the immune response potentiates tadpole tail regeneration during the refractory period Development, July 15, 2009; 136(14): 2323 - 2327. [Abstract] [Full Text] [PDF]

				J. Morokuma, D. Blackiston, D. S. Adams, G. Seebohm, B. Trimmer, and M. Levin Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells PNAS, October 28, 2008; 105(43): 16608 - 16613. [Abstract] [Full Text] [PDF]

				N. J. Oviedo, C. L. Nicolas, D. S. Adams, and M. Levin Live Imaging of Planarian Membrane Potential Using DiBAC4(3) CSH Protocols, October 1, 2008; 2008(11): pdb.prot5055 - pdb.prot5055. [Abstract] [Full Text]

				A.-S. Tseng and M. Levin Tail Regeneration in Xenopus laevis as a Model for Understanding Tissue Repair Journal of Dental Research, September 1, 2008; 87(9): 806 - 816. [Abstract] [Full Text] [PDF]

				V. P. Yin, J. M. Thomson, R. Thummel, D. R. Hyde, S. M. Hammond, and K. D. Poss Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish Genes & Dev., March 15, 2008; 22(6): 728 - 733. [Abstract] [Full Text] [PDF]

				J. M. W. Slack The Spark of Life: Electricity and Regeneration Sci. Signal., September 25, 2007; 2007(405): pe54 - pe54. [Abstract] [Full Text] [PDF]

				N. J. Oviedo and M. Levin smedinx-11 is a planarian stem cell gap junction gene required for regeneration and homeostasis Development, September 1, 2007; 134(17): 3121 - 3131. [Abstract] [Full Text] [PDF]

				D. E. Ingber and M. Levin What lies at the interface of regenerative medicine and developmental biology? Development, July 15, 2007; 134(14): 2541 - 2547. [Abstract] [Full Text] [PDF]