How Does the Xenopus laevis Embryonic Cell Cycle Avoid Spatial Chaos?

Theoretical studies have shown that a deterministic biochemical oscillator can become chaotic when operating over a sufficiently large volume and have suggested that the Xenopus laevis cell cycle oscillator operates close to such a chaotic regime. To experimentally test this hypothesis, we decreased the speed of the post-fertilization calcium wave, which had been predicted to generate chaos. However, cell divisions were found to develop normally, and eggs developed into normal tadpoles. Motivated by these experiments, we carried out modeling studies to understand the prerequisites for the predicted spatial chaos. We showed that this type of spatial chaos requires oscillatory reaction dynamics with short pulse duration and postulated that the mitotic exit in Xenopus laevis is likely slow enough to avoid chaos. In systems with shorter pulses, chaos may be an important hazard, as in cardiac arrhythmias, or a useful feature, as in the pigmentation of certain mollusk shells.

[1]  Alvin Shrier,et al.  Spiral wave generation in heterogeneous excitable media. , 2002, Physical review letters.

[2]  G. Oster,et al.  A Model for Shell Patterns Based on Neural Activity , 2010 .

[3]  Yue-Xian Li,et al.  Stability of front solutions in inhomogeneous media , 2003 .

[4]  M P Nash,et al.  Self-organized pacemakers in a coupled reaction-diffusion-mechanics system. , 2005, Physical review letters.

[5]  H. Piwnica-Worms,et al.  Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. , 1992, Science.

[6]  A. Goldbeter,et al.  Alternating Oscillations and Chaos in a Model of Two Coupled Biochemical Oscillators Driving Successive Phases of the Cell Cycle , 1999, Annals of the New York Academy of Sciences.

[7]  H. Meinhardt,et al.  A model for pattern formation on the shells of molluscs , 1987 .

[8]  J. NAGUMOt,et al.  An Active Pulse Transmission Line Simulating Nerve Axon , 2006 .

[9]  T. Coleman,et al.  Two distinct mechanisms for negative regulation of the Wee1 protein kinase. , 1993, The EMBO journal.

[10]  R. Nuccitelli,et al.  An elevated free cytosolic Ca2+ wave follows fertilization in eggs of the frog, Xenopus laevis , 1985, The Journal of cell biology.

[11]  Lendert Gelens,et al.  Spatial trigger waves: positive feedback gets you a long way , 2014, Molecular biology of the cell.

[12]  J. Tyson,et al.  Numerical analysis of a comprehensive model of M-phase control in Xenopus oocyte extracts and intact embryos. , 1993, Journal of cell science.

[13]  Leon Glass,et al.  How to Tell a Target from a Spiral: The Two Probe Problem , 1999 .

[14]  R. FitzHugh Impulses and Physiological States in Theoretical Models of Nerve Membrane. , 1961, Biophysical journal.

[15]  Julie A. Theriot,et al.  Changes in Oscillatory Dynamics in the Cell Cycle of Early Xenopus laevis Embryos , 2014, PLoS biology.

[16]  T. Coleman,et al.  Myt1: A Membrane-Associated Inhibitory Kinase That Phosphorylates Cdc2 on Both Threonine-14 and Tyrosine-15 , 1995, Science.

[17]  B. Deng The existence of infinitely many traveling front and back waves in the FitzHugh-Nagumo equations , 1991 .

[18]  D. Chialvo,et al.  Non-linear dynamics of cardiac excitation and impulse propagation , 1987, Nature.

[19]  Martyn P. Nash,et al.  Pacemakers in a Reaction-Diffusion Mechanics System , 2007 .

[20]  John J. Tyson,et al.  Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[21]  E. Karsenti,et al.  Phosphorylation and activation of human cdc25‐C by cdc2‐‐cyclin B and its involvement in the self‐amplification of MPF at mitosis. , 1993, The EMBO journal.

[22]  Flavio H. Fenton,et al.  SPATIOTEMPORAL CONTROL OF WAVE INSTABILITIES IN CARDIAC TISSUE , 1999 .

[23]  J. Ferrell,et al.  Ultrasensitivity in the Regulation of Cdc25C by Cdk1. , 2011, Molecular cell.

[24]  J. Bell,et al.  Study of propagation along nonuniform excitable fibers. , 1994, Mathematical biosciences.

[25]  Yue-Xian Li,et al.  Tango waves in a bidomain model of fertilization calcium waves , 2003 .

[26]  Marc W. Kirschner,et al.  How Proteolysis Drives the Cell Cycle , 1996, Science.

[27]  J. Keener,et al.  Singular perturbation theory of traveling waves in excitable media (a review) , 1988 .

[28]  Qiong Yang,et al.  The Cdk1–APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch , 2013, Nature Cell Biology.

[29]  James E. Ferrell,et al.  Systems-Level Dissection of the Cell-Cycle Oscillator: Bypassing Positive Feedback Produces Damped Oscillations , 2005, Cell.

[30]  Alvin Shrier,et al.  The role of heterogeneities and intercellular coupling in wave propagation in cardiac tissue , 2006, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[31]  James E. Ferrell,et al.  Mitotic trigger waves and the spatial coordination of the Xenopus cell cycle , 2013, Nature.

[32]  A. Winfree Electrical instability in cardiac muscle: phase singularities and rotors. , 1989, Journal of theoretical biology.

[33]  Stephen Wolfram,et al.  Cellular automata as models of complexity , 1984, Nature.

[34]  P. Russell,et al.  Human Wee1 kinase inhibits cell division by phosphorylating p34cdc2 exclusively on Tyr15. , 1993, The EMBO journal.

[35]  B. Novák,et al.  The role of APC/C inhibitor Emi2/XErp1 in oscillatory dynamics of early embryonic cell cycles. , 2013, Biophysical chemistry.

[36]  A. Panfilov,et al.  Anomalous drift of spiral waves in heterogeneous excitable media. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[37]  J. Minshull,et al.  Translation of cyclin mRNA is necessary for extracts of activated Xenopus eggs to enter mitosis , 1989, Cell.

[38]  Ned S. Wingreen,et al.  Does the Potential for Chaos Constrain the Embryonic Cell-Cycle Oscillator? , 2011, PLoS Comput. Biol..

[39]  R. Nuccitelli,et al.  Characterization of the sperm-induced calcium wave in Xenopus eggs using confocal microscopy. , 1998, Biophysical journal.

[40]  Hans Meinhardt,et al.  The Algorithmic Beauty of Sea Shells , 1998, The Virtual Laboratory.

[41]  Metta Riebesell,et al.  The Early Development of Xenopus Laevis: An Atlas of the Histology , 1991 .

[42]  Eduardo Sontag,et al.  Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2 , 2003, Nature Cell Biology.

[43]  James E. Ferrell,et al.  Substrate Competition as a Source of Ultrasensitivity in the Inactivation of Wee1 , 2007, Cell.

[44]  J. Gerhart Mechanisms Regulating Pattern Formation in the Amphibian Egg and Early Embryo , 1980 .

[45]  Andrew W. Murray,et al.  Cyclin synthesis drives the early embryonic cell cycle , 1989, Nature.

[46]  T. Coleman,et al.  Cell cycle regulation of a Xenopus Wee1-like kinase. , 1995, Molecular biology of the cell.

[47]  Balth van der Pol Jun Docts. Sc.,et al.  LXXII. The heartbeat considered as a relaxation oscillation, and an electrical model of the heart , 1928 .

[48]  K. H. Norian An Electrical Model of the Heart , 2008 .

[49]  J. Bonnet,et al.  Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis , 2008, Cell cycle.

[50]  G Duckett,et al.  Modeling the dynamics of cardiac action potentials. , 2000, Physical review letters.

[51]  A. Babloyantz Mechanisms of target and spiral wave propagation in single cells. , 1994, Chaos.

[52]  John J. Tyson,et al.  Modeling the Cell Division Cycle: M-phase Trigger, Oscillations, and Size Control , 1993 .

[53]  Rabinovitch,et al.  A Model for the Propagation of Action Potentials in Non-Uniformly Excitable Media. , 1999, Journal of theoretical biology.

[54]  C F Starmer,et al.  Vulnerability in an excitable medium: analytical and numerical studies of initiating unidirectional propagation. , 1993, Biophysical journal.

[55]  J. Pines,et al.  Active cyclin B1–Cdk1 first appears on centrosomes in prophase , 2003, Nature Cell Biology.

[56]  Marc W. Kirschner,et al.  Cyclin activation of p34 cdc2 , 1990, Cell.

[57]  Bard Ermentrout,et al.  Reflected Waves in an Inhomogeneous Excitable Medium , 1996, SIAM J. Appl. Math..

[58]  Hans Meinhardt,et al.  The Algorithmic Beauty of Sea Shells , 2003, The Virtual Laboratory.

[59]  Victoria Booth,et al.  Understanding Propagation Failure as a Slow Capture Near a Limit Point , 1995, SIAM J. Appl. Math..