Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Some developmental events rely on an electrophoretic force to produce morphogenetic gradients. To quantitatively explore the dynamics of this process, we constructed a stochastic model of an early phase of left-right patterning: serotonin movement through the gap junction-coupled blastomeres of the Xenopus embryo. Particle-tracking simulations showed that a left-right gradient is formed rapidly, quickly reaching a final stable level. The voltage difference was critical for producing a morphogen gradient of the right steepness; gap junctional connectivity and morphogen mass determined the timing of the gradient. Endogenous electrophoresis drives approximately 50% of the particles across more than one cell width, and approximately 20% can travel across half the embryo. The stochastic behavior of the resulting gradients exhibited unexpected complexity among blastomeres' morphogen content, and showed how spatiotemporal variability within individual cells resulted in robust and consistent gradients across the embryonic left-right axis. Analysis of the distribution profile of gradient gain values made quantitative predictions about the conditions that result in the observed background level of laterality defects in unperturbed frog embryos. This work provides a general model that can be used to quantitatively analyze the unexpectedly complex dynamics of morphogens in a wide variety of systems.
Adams,
A new tool for tissue engineers: ions as regulators of morphogenesis during development and regeneration.
2008, Pubmed
Adams,
A new tool for tissue engineers: ions as regulators of morphogenesis during development and regeneration.
2008,
Pubmed Adams,
Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates.
2006,
Pubmed
,
Xenbase Anderson,
A gap junctionally transmitted epithelial cell signal regulates endocytic yolk uptake in Oncopeltus fasciatus.
2001,
Pubmed Ashe,
The interpretation of morphogen gradients.
2006,
Pubmed Ashe,
Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo.
2000,
Pubmed 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 Bao,
Pannexin membrane channels are mechanosensitive conduits for ATP.
2004,
Pubmed
,
Xenbase Barkai,
'Big frog, small frog'--maintaining proportions in embryonic development: delivered on 2 July 2008 at the 33rd FEBS Congress in Athens, Greece.
2009,
Pubmed
,
Xenbase Blomstrand,
Extent of intercellular calcium wave propagation is related to gap junction permeability and level of connexin-43 expression in astrocytes in primary cultures from four brain regions.
1999,
Pubmed Brooks,
Calmodulin transmitted through gap junctions stimulates endocytic incorporation of yolk precursors in insect oocytes.
2004,
Pubmed Chen,
The zebrafish Nodal signal Squint functions as a morphogen.
2001,
Pubmed Cooper,
Electrophoretic repatterning of charged cytoplasmic molecules within tissues coupled by gap junctions by externally applied electric fields.
1989,
Pubmed Cooper,
Gap junctions increase the sensitivity of tissue cells to exogenous electric fields.
1984,
Pubmed Coppey,
Modeling the bicoid gradient: diffusion and reversible nuclear trapping of a stable protein.
2007,
Pubmed Dyson,
The interpretation of position in a morphogen gradient as revealed by occupancy of activin receptors.
1998,
Pubmed
,
Xenbase Eichele,
Characterization of concentration gradients of a morphogenetically active retinoid in the chick limb bud.
1987,
Pubmed Eldar,
Self-enhanced ligand degradation underlies robustness of morphogen gradients.
2003,
Pubmed Eldar,
Elucidating mechanisms underlying robustness of morphogen gradients.
2004,
Pubmed Emanuelsson,
Intercellular voltage gradient between oocyte and nurse cell in a polychaete.
1985,
Pubmed England,
Morphogen gradient from a noisy source.
2005,
Pubmed Esser,
Mathematical model of morphogen electrophoresis through gap junctions.
2006,
Pubmed
,
Xenbase Francis,
Connexin diversity and gap junction regulation by pHi.
1999,
Pubmed
,
Xenbase French,
Pattern regulation in epimorphic fields.
1976,
Pubmed Fukumoto,
Serotonin signaling is a very early step in patterning of the left-right axis in chick and frog embryos.
2005,
Pubmed
,
Xenbase Fukumoto,
Serotonin transporter function is an early step in left-right patterning in chick and frog embryos.
2005,
Pubmed
,
Xenbase Goldberg,
Selective permeability of gap junction channels.
2004,
Pubmed González,
Molecular basis of voltage dependence of connexin channels: an integrative appraisal.
2007,
Pubmed Green,
Retinoic acid: the morphogen of the main body axis?
1990,
Pubmed
,
Xenbase Green,
Morphogen gradients, positional information, and Xenopus: interplay of theory and experiment.
2002,
Pubmed
,
Xenbase Gurdon,
Single cells can sense their position in a morphogen gradient.
1999,
Pubmed
,
Xenbase Hanna,
Gap junctions in early amphibian embryos.
1980,
Pubmed Hille,
Ionic channels in excitable membranes. Current problems and biophysical approaches.
1978,
Pubmed Hirst-Jensen,
Characterization of the pH-dependent interaction between the gap junction protein connexin43 carboxyl terminus and cytoplasmic loop domains.
2007,
Pubmed Ingber,
What lies at the interface of regenerative medicine and developmental biology?
2007,
Pubmed Jaffe,
Large electrical currents traverse developing Ceropia follicles.
1979,
Pubmed Jaffe,
Local cation entry and self-electrophoresis as an intracellular localization mechanism.
1974,
Pubmed Kema,
Clinical chemistry of serotonin and metabolites.
2000,
Pubmed Kerszberg,
Specifying positional information in the embryo: looking beyond morphogens.
2007,
Pubmed Lange,
The mechanism of anterior-posterior polarity control in planarians.
1978,
Pubmed Levin,
Is the early left-right axis like a plant, a kidney, or a neuron? The integration of physiological signals in embryonic asymmetry.
2006,
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,
Large-scale biophysics: ion flows and regeneration.
2007,
Pubmed Levin,
Gap junctional communication in morphogenesis.
2007,
Pubmed Levin,
Of minds and embryos: left-right asymmetry and the serotonergic controls of pre-neural morphogenesis.
2006,
Pubmed Levin,
Left-right asymmetry in embryonic development: a comprehensive review.
2005,
Pubmed Levin,
Gap junctions are involved in the early generation of left-right asymmetry.
1998,
Pubmed
,
Xenbase Levin,
Left-right patterning from the inside out: widespread evidence for intracellular control.
2007,
Pubmed Levin,
Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning.
2002,
Pubmed
,
Xenbase Levitt,
General continuum theory for multiion channel. I. Theory.
1991,
Pubmed Lewis,
From signals to patterns: space, time, and mathematics in developmental biology.
2008,
Pubmed
,
Xenbase Maiti,
Measuring serotonin distribution in live cells with three-photon excitation.
1997,
Pubmed Mastro,
Diffusion of a small molecule in the cytoplasm of mammalian cells.
1984,
Pubmed Momose-Sato,
Optical imaging of large-scale correlated wave activity in the developing rat CNS.
2005,
Pubmed Moreno,
Gap junction channel gating modulated through protein phosphorylation.
2007,
Pubmed Morokuma,
KCNQ1 and KCNE1 K+ channel components are involved in early left-right patterning in Xenopus laevis embryos.
2008,
Pubmed
,
Xenbase Nakamura,
Generation of robust left-right asymmetry in the mouse embryo requires a self-enhancement and lateral-inhibition system.
2006,
Pubmed Nicholson,
Gap junctions - from cell to molecule.
2003,
Pubmed Nuccitelli,
On electrical currents in development.
1986,
Pubmed Poo,
Lateral electrophoresis and diffusion of Concanavalin A receptors in the membrane of embryonic muscle cell.
1978,
Pubmed
,
Xenbase Poo,
Electrophoresis of concanavalin A receptors along embryonic muscle cell membrane.
1977,
Pubmed
,
Xenbase Reeves,
Quantitative models of developmental pattern formation.
2006,
Pubmed Retamal,
Opening of connexin 43 hemichannels is increased by lowering intracellular redox potential.
2007,
Pubmed Scadding,
Retinoic acid gradients during limb regeneration.
1994,
Pubmed
,
Xenbase Schiffmann,
An hypothesis: phosphorylation fields as the source of positional information and cell differentiation--(cAMP, ATP) as the universal morphogenetic Turing couple.
1991,
Pubmed Schiffmann,
The second messenger system as the morphogenetic field.
1989,
Pubmed Sharp,
Computer simulations of the diffusion of a substrate to an active site of an enzyme.
1987,
Pubmed Shi,
Three-dimensional gradients of voltage during development of the nervous system as invisible coordinates for the establishment of embryonic pattern.
1995,
Pubmed Söhl,
Expression and functions of neuronal gap junctions.
2005,
Pubmed Spéder,
Strategies to establish left/right asymmetry in vertebrates and invertebrates.
2007,
Pubmed Spray,
Gap junctional conductance is a simple and sensitive function of intracellular pH.
1981,
Pubmed Suadicani,
Gap junction channels coordinate the propagation of intercellular Ca2+ signals generated by P2Y receptor activation.
2004,
Pubmed Teleman,
Shaping morphogen gradients.
2001,
Pubmed Veenstra,
Selective dye and ionic permeability of gap junction channels formed by connexin45.
1994,
Pubmed Veenstra,
Selectivity of connexin-specific gap junctions does not correlate with channel conductance.
1995,
Pubmed Weber,
The permeability of gap junction channels to probes of different size is dependent on connexin composition and permeant-pore affinities.
2004,
Pubmed
,
Xenbase Wolpert,
Positional information and the spatial pattern of cellular differentiation.
1969,
Pubmed Woodruff,
Polarized intercellular bridges in ovarian follicles of the cecropia moth.
1973,
Pubmed Woodruff,
Electrophoresis of proteins in intercellular bridges.
1980,
Pubmed Woodruff,
Electrically mediated protein movement inDrosophila follicles.
1988,
Pubmed WOODRUFF,
Charge Dependent Distribution of Endogenous Proteins within Vitellogenic Ovarian Follicles of Actias luna.
1997,
Pubmed
