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Review
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Organization of Early Frog Embryos by Chemical Waves Emanating From Centrosomes

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Review

Organization of Early Frog Embryos by Chemical Waves Emanating From Centrosomes

Keisuke Ishihara et al. Philos Trans R Soc Lond B Biol Sci.

Abstract

The large cells in early vertebrate development face an extreme physical challenge in organizing their cytoplasm. For example, amphibian embryos have to divide cytoplasm that spans hundreds of micrometres every 30 min according to a precise geometry, a remarkable accomplishment given the extreme difference between molecular and cellular scales in this system. How do the biochemical reactions occurring at the molecular scale lead to this emergent behaviour of the cell as a whole? Based on recent findings, we propose that the centrosome plays a crucial role by initiating two autocatalytic reactions that travel across the large cytoplasm as chemical waves. Waves of mitotic entry and exit propagate out from centrosomes using the Cdk1 oscillator to coordinate the timing of cell division. Waves of microtubule-stimulated microtubule nucleation propagate out to assemble large asters that position spindles for the following mitosis and establish cleavage plane geometry. By initiating these chemical waves, the centrosome rapidly organizes the large cytoplasm during the short embryonic cell cycle, which would be impossible using more conventional mechanisms such as diffusion or nucleation by structural templating. Large embryo cells provide valuable insights to how cells control chemical waves, which may be a general principle for cytoplasmic organization.

Keywords: cell cycle; centrosome; chemical wave; embryo; microtubule aster.

Figures

Figure 1.
Figure 1.
Chemical waves initiated by the centrosome. (a) In our hypothesis, the centrosome (yellow circle) triggers two types of autocatalytic reactions that spread radially outward through the cytoplasm. Cell cycle waves are mediated by mitotic Cdk1 feedback regulation, while aster growth is mediated by microtubule-stimulated microtubule assembly. (bd) Requirements of the cytoplasm to support chemical waves. Curves show spatio-temporal dynamics of biochemical activity according to the equations shown, which are non-unique examples of each situation. (b) Growth, or an autocatalytic reaction, with saturation results in local amplification of activity. (c) Diffusion results in the homogenization of activity. (d) When growth and diffusion are coupled, a propagating front or a chemical wave, may be observed. Equations are shown for the one-dimensional case, but the long time-scale prediction of a propagating wavefront is remarkably robust for higher dimensions, radial geometry and a range of initial conditions. Note that the logistic growth term in (d) represents a broad class of reactions with positive feedback, including the growth phase of excitable/bistable kinetics.
Figure 2.
Figure 2.
Cell cycle waves in large cytoplasm. (a) In fertilized frog embryos, SCWs travel from the animal to the vegetal pole. Regions of high (pink) and low (purple) mitotic Cdk1 activity coexist in the common cytoplasm. Centrosomes (yellow) reside in the animal half of the embryo until the eight-cell stage. Illustration adapted from [29]. (b,c) Reconstitution of cell cycle waves in cycling Xenopus egg extract filled in a Teflon tube. Reproduced with permission from Nature [1]. Copyright © 2013 Macmillan Publishers Ltd. (b) Cell cycle state is monitored by nuclear envelope dynamics with GFP fused to nuclear localization sequence. (c) Spatial dynamics of cell cycle inside tube of length 3 mm. Nuclear envelope breakdown (red points) and reformation (blue points) indicate whether the cytoplasm is in mitosis (pink) or interphase (purple). The sloped lines indicate cell cycle waves and their velocities.
Figure 3.
Figure 3.
Growth of microtubule asters in the large interphase cytoplasm of frog zygotes. (ad) Growth and interaction of asters in the first division in Xenopus laevis. Fertilized eggs were fixed, stained for tubulin and imaged from the animal pole by a confocal microscope as described [2,3]. (a) Sperm aster during the interphase following fertilization. The sperm aster eventually covers the entire cytoplasm. (b) Metaphase of first mitosis (spindle magnified in inset). Aster size is limited at spindle poles. (c) Anaphase–telophase of first mitosis. Aster growth and interaction between asters originating from the same spindle. (d) Later telophase. Note the dense, bushy appearance of microtubules at the aster periphery, low microtubule density in the interaction zone. (eg) Models for aster growth in large cells. (e) Conventional radial elongation model. Microtubules polymerize outward from centrosomes (yellow). Microtubule density at the aster periphery decreases. (f) Nucleation away from the centrosome may occur on pre-existing microtubules or Golgi membranes (blue stacks). (g) Release and outward transport. Minus ends are released from the centrosomal nucleation site and microtubules slide outward (red arrows). (h) Reaction–diffusion model of microtubule aster expansion. v+, v are rates of polymerization and depolymerization. fcat and fres are catastrophe and rescue frequencies of the microtubule plus end.

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