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Bioelectric signals, particularly transmembrane voltage potentials (Vmem), play an important role in large-scale patterning during embryonic development. Endogenous bioelectric gradients across tissues function as instructive factors during eye, brain, and other morphogenetic processes. An important and still poorly-understood aspect is the control of cell behaviors by the voltage states of distant cell groups. Here, experimental alteration of endogenous Vmem was induced in Xenopus laevis embryos by misexpression of well-characterized ion channel mRNAs, a strategy often used to identify functional roles of Vmem gradients during embryonic development and regeneration. Immunofluorescence analysis (for activated caspase 3 and phosphor-histone H3P) on embryonic sections was used to characterize apoptosis and proliferation. Disrupting local bioelectric signals (within the developing neural tube region) increased caspase 3 and decreased H3P in the brain, resulting in brain mispatterning. Disrupting remote (ventral, non-neural region) bioelectric signals decreased caspase 3 and highly increased H3P within the brain, with normal brain patterning. Disrupting both the local and distant bioelectric signals produced antagonistic effects on caspase 3 and H3P. Thus, two components of bioelectric signals regulate apoptosis-proliferation balance within the developing brain and spinal cord: local (developing neural tube region) and distant (ventral non-neural region). Together, the local and long-range bioelectric signals create a binary control system capable of fine-tuning apoptosis and proliferation with the brain and spinal cord to achieve correct pattern and size control. Our data suggest a roadmap for utilizing bioelectric state as a diagnostic modality and convenient intervention parameter for birth defects and degenerative disease states of the CNS.
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26198142 ???displayArticle.pmcLink???PMC10505512 ???displayArticle.link???Int J Dev Biol ???displayArticle.grants???[+]
Adams,
Endogenous voltage gradients as mediators of cell-cell communication: strategies for investigating bioelectrical signals during pattern formation.
2013, Pubmed
Adams,
Endogenous voltage gradients as mediators of cell-cell communication: strategies for investigating bioelectrical signals during pattern formation.
2013,
Pubmed Adams,
H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration.
2007,
Pubmed
,
Xenbase Altmann,
Neural patterning in the vertebrate embryo.
2001,
Pubmed Anava,
The role of gap junction proteins in the development of neural network functional topology.
2013,
Pubmed Arya,
Cell death in development: Signaling pathways and core mechanisms.
2015,
Pubmed Aw,
The ATP-sensitive K(+)-channel (K(ATP)) controls early left-right patterning in Xenopus and chick embryos.
2010,
Pubmed
,
Xenbase Aw,
H,K-ATPase protein localization and Kir4.1 function reveal concordance of three axes during early determination of left-right asymmetry.
2008,
Pubmed
,
Xenbase Beane,
A chemical genetics approach reveals H,K-ATPase-mediated membrane voltage is required for planarian head regeneration.
2011,
Pubmed Beane,
Bioelectric signaling regulates head and organ size during planarian regeneration.
2013,
Pubmed Bergmann,
Apoptosis, stem cells, and tissue regeneration.
2010,
Pubmed
,
Xenbase Bertoli,
Activation and deactivation properties of rat brain K+ channels of the Shaker-related subfamily.
1994,
Pubmed
,
Xenbase Binggeli,
Membrane potentials and sodium channels: hypotheses for growth regulation and cancer formation based on changes in sodium channels and gap junctions.
1986,
Pubmed Blackiston,
Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway.
2011,
Pubmed
,
Xenbase Blackiston,
High-throughput Xenopus laevis immunohistochemistry using agarose sections.
2010,
Pubmed
,
Xenbase Blackiston,
A novel method for inducing nerve growth via modulation of host resting potential: gap junction-mediated and serotonergic signaling mechanisms.
2015,
Pubmed
,
Xenbase Blackiston,
Bioelectric controls of cell proliferation: ion channels, membrane voltage and the cell cycle.
2009,
Pubmed Borodinsky,
Activity-dependent homeostatic specification of transmitter expression in embryonic neurons.
2004,
Pubmed
,
Xenbase Brackenbury,
Voltage-gated sodium channels and metastatic disease.
2012,
Pubmed Cao,
Endogenous electric currents might guide rostral migration of neuroblasts.
2013,
Pubmed Chan,
Proliferation and apoptosis in the developing human neocortex.
2002,
Pubmed Chera,
Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration.
2009,
Pubmed Chernet,
Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model.
2013,
Pubmed
,
Xenbase Chernet,
Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in Xenopus laevis embryos.
2014,
Pubmed
,
Xenbase Chernet,
Transmembrane voltage potential of somatic cells controls oncogene-mediated tumorigenesis at long-range.
2014,
Pubmed
,
Xenbase Copp,
Genetics and development of neural tube defects.
2010,
Pubmed Cowan,
Caspase-3 and caspase-9 mediate developmental apoptosis in the mouse olfactory system.
2004,
Pubmed de Felipe,
E unum pluribus: multiple proteins from a self-processing polyprotein.
2006,
Pubmed Deisseroth,
Excitation-neurogenesis coupling in adult neural stem/progenitor cells.
2004,
Pubmed Detrait,
Human neural tube defects: developmental biology, epidemiology, and genetics.
2005,
Pubmed Ding,
Involvement of cationic channels in proliferation and migration of human mesenchymal stem cells.
2012,
Pubmed Doğanli,
α3Na+/K+-ATPase deficiency causes brain ventricle dilation and abrupt embryonic motility in zebrafish.
2013,
Pubmed Fuhrmann,
Eye morphogenesis and patterning of the optic vesicle.
2010,
Pubmed Fukumoto,
Serotonin transporter function is an early step in left-right patterning in chick and frog embryos.
2005,
Pubmed
,
Xenbase Goldman,
Motor stereotypies and volumetric brain alterations in children with Autistic Disorder.
2013,
Pubmed Götz,
The cell biology of neurogenesis.
2005,
Pubmed Harada,
Molecular regulation of visual system development: more than meets the eye.
2007,
Pubmed Harvey,
The hippo pathway.
2012,
Pubmed Higashimori,
Role of Kir4.1 channels in growth control of glia.
2007,
Pubmed Jaffe,
Control of development by ionic currents.
1979,
Pubmed Joseph,
Molecular control of brain size: regulators of neural stem cell life, death and beyond.
2010,
Pubmed Konig,
Membrane hyperpolarization triggers myogenin and myocyte enhancer factor-2 expression during human myoblast differentiation.
2004,
Pubmed Kozorovitskiy,
Recurrent network activity drives striatal synaptogenesis.
2012,
Pubmed Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase Lauder,
Roles for serotonin in neuroembryogenesis.
1981,
Pubmed Levin,
Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning.
2002,
Pubmed
,
Xenbase Levin,
Errors of geometry: regeneration in a broader perspective.
2009,
Pubmed Levin,
Reprogramming cells and tissue patterning via bioelectrical pathways: molecular mechanisms and biomedical opportunities.
2013,
Pubmed Levin,
Endogenous bioelectrical networks store non-genetic patterning information during development and regeneration.
2014,
Pubmed Levin,
Molecular bioelectricity: how endogenous voltage potentials control cell behavior and instruct pattern regulation in vivo.
2014,
Pubmed Levin,
Gap junction-mediated transfer of left-right patterning signals in the early chick blastoderm is upstream of Shh asymmetry in the node.
1999,
Pubmed
,
Xenbase Levin,
Regulation of cell behavior and tissue patterning by bioelectrical signals: challenges and opportunities for biomedical engineering.
2012,
Pubmed Lin,
Transgenic analysis of signaling pathways required for Xenopus tadpole spinal cord and muscle regeneration.
2012,
Pubmed
,
Xenbase Lobikin,
Resting potential, oncogene-induced tumorigenesis, and metastasis: the bioelectric basis of cancer in vivo.
2012,
Pubmed
,
Xenbase MARSH,
Electrical control of growth polarity in regenerating Dugesia tigrina.
1947,
Pubmed Marsh-Armstrong,
Germ-line transmission of transgenes in Xenopus laevis.
1999,
Pubmed
,
Xenbase McCaig,
Controlling cell behavior electrically: current views and future potential.
2005,
Pubmed Miura,
Active participation of cell death in development and organismal homeostasis.
2011,
Pubmed Moody,
Fates of the blastomeres of the 32-cell-stage Xenopus embryo.
1987,
Pubmed
,
Xenbase Ng,
Role of voltage-gated potassium channels in the fate determination of embryonic stem cells.
2010,
Pubmed Nilius,
Potassium channels and regulation of proliferation of human melanoma cells.
1992,
Pubmed Nonomura,
Local apoptosis modulates early mammalian brain development through the elimination of morphogen-producing cells.
2013,
Pubmed Northcutt,
The Agnathan ark: the origin of craniate brains.
1996,
Pubmed Northcutt,
Origin of the isthmus? A comparison of the brains of lancelets and vertebrates.
2003,
Pubmed Nuckels,
The vacuolar-ATPase complex regulates retinoblast proliferation and survival, photoreceptor morphogenesis, and pigmentation in the zebrafish eye.
2009,
Pubmed Pai,
Endogenous gradients of resting potential instructively pattern embryonic neural tissue via Notch signaling and regulation of proliferation.
2015,
Pubmed
,
Xenbase Pai,
Transmembrane voltage potential controls embryonic eye patterning in Xenopus laevis.
2012,
Pubmed
,
Xenbase Pai,
Neurally Derived Tissues in Xenopus laevis Embryos Exhibit a Consistent Bioelectrical Left-Right Asymmetry.
2012,
Pubmed
,
Xenbase Palacios-Prado,
Heterotypic gap junction channels as voltage-sensitive valves for intercellular signaling.
2009,
Pubmed Penn,
Brain waves and brain wiring: the role of endogenous and sensory-driven neural activity in development.
1999,
Pubmed Perathoner,
Bioelectric signaling regulates size in zebrafish fins.
2014,
Pubmed
,
Xenbase Pérez-Garijo,
Apoptotic cells can induce non-autonomous apoptosis through the TNF pathway.
2013,
Pubmed Porter,
Emerging roles of caspase-3 in apoptosis.
1999,
Pubmed Pratt,
Modeling human neurodevelopmental disorders in the Xenopus tadpole: from mechanisms to therapeutic targets.
2013,
Pubmed
,
Xenbase Rakic,
Programmed cell death in the developing human telencephalon.
2000,
Pubmed Saka,
Spatial and temporal patterns of cell division during early Xenopus embryogenesis.
2001,
Pubmed
,
Xenbase Sánchez Alvarado,
The freshwater planarian Schmidtea mediterranea: embryogenesis, stem cells and regeneration.
2003,
Pubmed Shitamukai,
Control of asymmetric cell division of mammalian neural progenitors.
2012,
Pubmed Sowers,
Electric Fields in Vertebrate Repair. Natural and Applied Voltages in Vertebrate Regeneration and Healing. Richard B. Borgens, Kenneth R. Robinson, Joseph W. Vanable, Jr., and Michael E. McGinnis, with Colin D. McCaig. Liss, New York, 1989. xxiv, 310 pp., illus. $69.50.
1990,
Pubmed Stanger,
The biology of organ size determination.
2008,
Pubmed Stanger,
Organ size determination and the limits of regulation.
2008,
Pubmed Strutz-Seebohm,
Comparison of potent Kv1.5 potassium channel inhibitors reveals the molecular basis for blocking kinetics and binding mode.
2007,
Pubmed Sundelacruz,
Membrane potential controls adipogenic and osteogenic differentiation of mesenchymal stem cells.
2008,
Pubmed Sundelacruz,
Role of membrane potential in the regulation of cell proliferation and differentiation.
2009,
Pubmed Sundelacruz,
Bioelectric modulation of wound healing in a 3D in vitro model of tissue-engineered bone.
2013,
Pubmed Swapna,
Interplay between electrical activity and bone morphogenetic protein signaling regulates spinal neuron differentiation.
2012,
Pubmed
,
Xenbase Szymczak-Workman,
Design and construction of 2A peptide-linked multicistronic vectors.
2012,
Pubmed Tannahill,
Role of morphogens in brain growth.
2005,
Pubmed Tseng,
Apoptosis is required during early stages of tail regeneration in Xenopus laevis.
2007,
Pubmed
,
Xenbase Tseng,
Cracking the bioelectric code: Probing endogenous ionic controls of pattern formation.
2013,
Pubmed Tseng,
Induction of vertebrate regeneration by a transient sodium current.
2010,
Pubmed
,
Xenbase Tsuda,
Inhibitory effect of M50054, a novel inhibitor of apoptosis, on anti-Fas-antibody-induced hepatitis and chemotherapy-induced alopecia.
2001,
Pubmed Vandenberg,
V-ATPase-dependent ectodermal voltage and pH regionalization are required for craniofacial morphogenesis.
2011,
Pubmed
,
Xenbase van Vliet,
Hyperpolarization induces differentiation in human cardiomyocyte progenitor cells.
2010,
Pubmed Verselis,
A voltage-dependent gap junction in Drosophila melanogaster.
1991,
Pubmed Wallingford,
Planar cell polarity, ciliogenesis and neural tube defects.
2006,
Pubmed Warner,
The role of gap junctions in amphibian development.
1985,
Pubmed
,
Xenbase Yang,
Membrane potential and cancer progression.
2013,
Pubmed Zhang,
Regulation of cell proliferation of human induced pluripotent stem cell-derived mesenchymal stem cells via ether-à-go-go 1 (hEAG1) potassium channel.
2012,
Pubmed Zhao,
The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal.
2011,
Pubmed Zhao,
Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN.
2006,
Pubmed Zuber,
Eye field specification in Xenopus laevis.
2010,
Pubmed
,
Xenbase
