The Role of Early Bioelectric Signals in the Regeneration of Planarian Anterior/Posterior Polarity. Author: Durant F1, Bischof J1, Fields C1, Morokuma J1, LaPalme J1, Hoi A1, Levin M2 Affiliation: <sup>1</sup>Allen Discovery Center at Tufts University, Department of Biology, Tufts University, Medford, Massachusetts. <sup>2</sup>Allen Discovery Center at Tufts University, Department of Biology, Tufts University, Medford, Massachusetts. Electronic address: michael.levin@tufts.edu. Conference/Journal: Biophys J. Date published: 2019 Feb 1 Other: Pages: S0006-3495(19)30065-7 , Special Notes: doi: 10.1016/j.bpj.2019.01.029. [Epub ahead of print] , Word Count: 205 Axial patterning during planarian regeneration relies on a transcriptional circuit that confers distinct positional information on the two ends of an amputated fragment. The earliest known elements of this system begin demarcating differences between anterior and posterior wounds by 6 h postamputation. However, it is still unknown what upstream events break the axial symmetry, allowing a mutual repressor system to establish invariant, distinct biochemical states at the anterior and posterior ends. Here, we show that bioelectric signaling at 3 h is crucial for the formation of proper anterior-posterior polarity in planaria. Briefly manipulating the endogenous bioelectric state by depolarizing the injured tissue during the first 3 h of regeneration alters gene expression by 6 h postamputation and leads to a double-headed phenotype upon regeneration despite confirmed washout of ionophores from tissue. These data reveal a primary functional role for resting membrane potential taking place within the first 3 h after injury and kick-starting the downstream pattern of events that elaborate anatomy over the following 10 days. We propose a simple model of molecular-genetic mechanisms to explain how physiological events taking place immediately after injury regulate the spatial distribution of downstream gene expression and anatomy of regenerating planaria. Copyright © 2019 Biophysical Society. Published by Elsevier Inc. All rights reserved. PMID: 30799071 DOI: 10.1016/j.bpj.2019.01.029