What is bioelectricity?

A fundamental question in biology is how cells communicate to fashion and repair complex biological structures and tissues.  It is well established that cells communicate through biochemical cues.  However, compelling evidence suggests that cells and tissues of all types use ion fluxes to communicate electrically as well.  In addition, it is now clear that this method of communication is essential to proper development, regeneration, cancer suppression, and tissue homeostasis.  The field of developmental bioelectricity focuses on the regulation of cell-, tissue-, and organ-level patterning and function, as the result of endogenous electrically-mediated signaling events.  This field is distinct from a) neural bioelectricity (classically termed electrophysiology), which refers to the rapid and transient spiking in well-recognized excitable cells like neurons and myocytes; b) bioelectromagnetics, which refers to the effects of applied electromagnetic radiation; and c) endogenous electromagnetics, such as biophoton emission and magnetite.  While endogenous ionic phenomena and the effects of applied fields have been known for decades, there has been an explosion of new molecular-level and computational work in the past 5–10 years to establish this new interdisciplinary field, which is ripe for its first focused meeting.

 
Dynamic control of complex anatomical pattern is a multi-scale process that occurs during embryogenesis, regeneration, metamorphosis, remodeling, and cancer suppression. Individual cells and cell networks must coordinate their activity toward specific tissue- and organ-level morphological outcomes. These processes take place through three integrated layers: 1) gene-regulatory networks comprised of transcriptional circuits and diffusible biochemical signals, 2) physical forces – biomechanical processes by which tensions and stresses implement morphological computation, and 3) bioelectric networks – neural-like dynamics in gap junction-coupled tissues expressing ion channels and pumps. Each of these layers processes information and implements emergent complexity at cell, tissue, organ, and whole body axis levels. They are coupled, with bi-directional functional links between each, and unique roles in decision-making and implementation of pattern control. In this way, physics, chemistry, and computer science interplay to enable biological systems to regulate their own structure and function with a high degree of adaptive robustness. Poster created by Ben Oldroyd.

Dynamic control of complex anatomical pattern is a multi-scale process that occurs during embryogenesis, regeneration, metamorphosis, remodeling, and cancer suppression. Individual cells and cell networks must coordinate their activity toward specific tissue- and organ-level morphological outcomes. These processes take place through three integrated layers: 1) gene-regulatory networks comprised of transcriptional circuits and diffusible biochemical signals, 2) physical forces – biomechanical processes by which tensions and stresses implement morphological computation, and 3) bioelectric networks – neural-like dynamics in gap junction-coupled tissues expressing ion channels and pumps. Each of these layers processes information and implements emergent complexity at cell, tissue, organ, and whole body axis levels. They are coupled, with bi-directional functional links between each, and unique roles in decision-making and implementation of pattern control. In this way, physics, chemistry, and computer science interplay to enable biological systems to regulate their own structure and function with a high degree of adaptive robustness. Poster created by Ben Oldroyd.

 

Recent work in several model organisms (including human, mouse, frog, zebrafish, fly, and planaria) has revealed a conserved role for bioelectric signaling in the development of heart, face, eye, brain, and other organs.  For example, human mutations that disrupt ion channels lead to morphological abnormalities (‘channelopathies’) such as cleft palate, small jaw, and digit patterning defects.  Numerous ion channel mutants in mice have been shown to recapitulate these craniofacial and digit patterning phenotypes.  Furthermore, bioelectric states of remote cells control tumorigenesis at the site of oncogene expression.  Screens have identified roles for ion channels in size control of structures such as the zebrafish fin, while focused gain-of-function studies have shown that body parts can be re-specified at the organ level – for example, creating functional eyes in gut endoderm.  As in behaving animal brains, developmental bioelectrics can integrate information across significant distance in the embryo; for example, the control of brain size by bioelectric states of ventral tissue and the control of tumorigenesis at the site of oncogene expression by bioelectric state of remote cells.  Recent molecular work has identified proton and sodium flux as being important for tail regeneration in Xenopus tadpoles and has revealed that regeneration of the entire tail (with spinal cord, muscle, etc.) can be triggered in a range of normally non-regenerative conditions by either molecular-genetic, pharmacological, or optogenetic methods.  In planaria, highly-regenerative flatworms, bioelectricity plays a key role in the control of stem cell behavior, size-control during remodeling, anterior-posterior polarity, and head shape.  Defection of cells from the normally tight coordination of activity towards an anatomical structure results in cancer; it is not surprising that bioelectricity – a key mechanism for coordinating cell growth and patterning – is a target often implicated in cancer and metastasis.  Recent work in amphibian models has shown that depolarization of resting potential can trigger metastatic behavior in normal cells, while hyperpolarization (induced by ion channel misexpression, drugs, or light) can suppress tumorigenesis induced by expression of human oncogenes.

Developmental bioelectricity is an exciting frontier topic that integrates across disciplines (physiology, molecular genetics of ion channels and pumps, biophysics, and computational modeling of bioelectric states) and applications (including embryogenesis, regeneration, cancer).  Recent progress in this field, which impacts our molecular understanding of embryogenesis, includes the development of novel molecular tools (including optogenetics), fundamental advances in basic science (linking bioelectrical gradients to upstream and downstream transcriptional and epigenetic pathways), and great promise in numerous biomedical applications (regenerative medicine, stem cell control, channelopathies, etc.).  Life is ultimately an electrochemical enterprise, and cutting-edge research in this field is progressing along several frontiers.  For example, researchers are probing how bioelectric signals are produced, how voltage changes at the cell membrane are able to regulate cell behavior, and what the genetic and epigenetic downstream targets of bioelectric signals are.  The recent work in bioelectricity on reprogramming tissues into complete organs, repairing birth defects in animal model systems, triggering regeneration, and eliciting multiple anatomical layouts from the same wild-type genome represents an important set of new directions of high relevance to the mission of the Society for Developmental Biology.  SDB members with interests in stem cell biology, regeneration, biophysical mechanisms of tissue organization, organ-level morphogenesis, and epigenetic inheritance of anatomical features will find interesting content in this symposium.