Analysis of the early embryonic cell cycles of Xenopus; regulation of cell cycle length by Xe-wee1 and Mos

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 237-248 ◽  
Author(s):  
M.S. Murakami ◽  
G.F. Vande Woude
Keyword(s):  
Cell Cycle ◽  
Tyrosine Phosphorylation ◽  
Cycle Length ◽  
Calcium Ionophore ◽  
Embryonic Cell ◽  
Dominant Negative ◽  
Cell Cycles ◽  
Dominant Negative Form ◽  
Regulation Of Cell Cycle ◽  
Cell Cycle Length

In Xenopus, cdc2 tyrosine phosphorylation is detected in the first 60–75 minute cell cycle but not in the next eleven cell cycles (cycles 2–12) which are only 30 minutes long. Here we report that the wee1/cdc25 ratio increases before the first mitotic interphase. We show that the Xe-wee1 protein is absent in stage VI oocytes and is expressed from meiosis II until gastrulation. A dominant negative form of Xe-wee1 (KM wee1) reduced the level cdc2 tyrosine phosphorylation and length of the first cycle. However, the ratio of wee1/cdc25 did not decrease after the first cycle and therefore did not explain the lack of cdc2 tyrosine phosphorylation in, nor the rapidity of, cycles 2–12. Furthermore, there was no evidence for a wee1/myt1 inhibitor in cycles 2–12. We examined the role of Mos in the first cycle because it is present during the first 20 minutes of this cycle. We arrested the rapid embryonic cell cycle (cycle 2 or 3) with Mos and restarted the cell cycle with calcium ionophore; the 30 minute cycle was converted into a 60 minute cycle, with cdc2 tyrosine phosphorylation. In addition, the injection of a non-degradable Mos (MBP-Mos) into the first cycle resulted in a dramatic elongation of this cycle (to 140 minutes). MBP-Mos did not delay DNA replication or the translation of cyclins A or B; it did, however, result in the marked accumulation of tyrosine phosphorylated cdc2. Thus, while the wee1/cdc25 ratio changes during development, these changes may not be responsible for the variety of cell cycles observed during early Xenopus embryogenesis. Our experiments indicate that Mos/MAPK can also contribute to cell cycle length.

scholarly journals PAR proteins direct asymmetry of the cell cycle regulators Polo-like kinase and Cdc25

2008 ◽  
Vol 180 (5) ◽  
pp. 877-885 ◽  
Author(s):  
David M. Rivers ◽  
Sergio Moreno ◽  
Mary Abraham ◽  
Julie Ahringer
Keyword(s):  
Cell Cycle ◽  
Cycle Length ◽  
Cell Cycle Regulators ◽  
Par Proteins ◽  
Early Embryos ◽  
Length Regulation ◽  
Cycle Lengths ◽  
Regulation Of Cell Cycle ◽  
Asymmetrically Distributed ◽  
Cell Cycle Length

Cell cycle lengths vary widely among different cells within an animal, yet mechanisms of cell cycle length regulation are poorly understood. In the Caenorhabditis elegans embryo, the first cell division produces two cells with different cell cycle lengths, which are dependent on the conserved partitioning-defective (PAR) polarity proteins. We show that two key cell cycle regulators, the Polo-like kinase PLK-1 and the cyclin-dependent kinase phosphatase CDC-25.1, are asymmetrically distributed in early embryos. PLK-1 shows anterior cytoplasmic enrichment and CDC-25.1 shows PLK-1–dependent enrichment in the anterior nucleus. Both proteins are required for normal mitotic progression. Furthermore, these asymmetries are controlled by PAR proteins and the muscle excess (MEX) proteins MEX-5/MEX-6, and the latter is linked to protein degradation. Our results support a model whereby the PAR and MEX-5/MEX-6 proteins asymmetrically control PLK-1 levels, which asymmetrically regulates CDC-25.1 to promote differences in cell cycle lengths. We suggest that control of Plk1 and Cdc25 may be relevant to regulation of cell cycle length in other developmental contexts.

scholarly journals A Branching Process to Characterize the Dynamics of Stem Cell Differentiation

2015 ◽  
Author(s):  
david miguez
Keyword(s):  
Mathematical Model ◽  
Cell Cycle ◽  
Stem Cell ◽  
Cycle Length ◽  
Branching Process ◽  
Stem Cell Differentiation ◽  
Stem Cell Population ◽  
Mathematical Framework ◽  
Average Cell ◽  
Cell Cycle Length

The understanding of the regulatory processes that orchestrate stem cell maintenance is a cornerstone in developmental biology. Here, we present a mathematical model based on a branching process formalism that predicts average rates of proliferative and differentiative divisions in a given stem cell population. In the context of vertebrate spinal neurogenesis, the model predicts complex non-monotonic variations in the rates of pp, pd and dd modes of division as well as in cell cycle length, in agreement with experimental results. Moreover, the model shows that the differentiation probability follows a binomial distribution, allowing us to develop equations to predict the rates of each mode of division. A phenomenological simulation of the developing spinal cord informed with the average cell cycle length and division rates predicted by the mathematical model reproduces the correct dynamics of proliferation and differentiation in terms of average numbers of progenitors and differentiated cells. Overall, the present mathematical framework represents a powerful tool to unveil the changes in the rate and mode of division of a given stem cell pool by simply quantifying numbers of cells at different times.

scholarly journals Long-range memory of growth and cycle progression correlates cell cycles in lineage trees

2018 ◽  
Author(s):  
Erika E Kuchen ◽  
Nils Becker ◽  
Nina Claudino ◽  
Thomas Höfer
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Mammalian Cell ◽  
Latent Variable ◽  
Cycle Length ◽  
Growth Control ◽  
Minimum Size ◽  
Cell Cycles ◽  
Lineage Trees

Mammalian cell proliferation is controlled by mitogens. However, how proliferation is coordinated with cell growth is poorly understood. Here we show that statistical properties of cell lineage trees – the cell-cycle length correlations within and across generations – reveal how cell growth controls proliferation. Analyzing extended lineage trees with latent-variable models, we find that two antagonistic heritable variables account for the observed cycle-length correlations. Using molecular perturbations of mTOR and MYC we identify these variables as cell size and regulatory license to divide, which are coupled through a minimum-size checkpoint. The checkpoint is relevant only for fast cell cycles, explaining why growth control of mammalian cell proliferation has remained elusive. Thus, correlated fluctuations of the cell cycle encode its regulation.

scholarly journals Theoretical Basis for the Measurement of Small Differences in the Length of the Cell Cycle between Two Cell Populations

2009 ◽  
Vol 2 (1) ◽  
pp. 95-100
Author(s):  
Juan Sebastian Yakisich
Keyword(s):  
Experimental Data ◽  
Cell Cycle ◽  
Theoretical Basis ◽  
Cycle Length ◽  
Cell Populations ◽  
Experimental Variability ◽  
Cell Strains ◽  
Novel Strategy ◽  
Cell Cycle Length

The length of the cell cycle (TC) is a tight regulated process and is important for proper development and homeostasis. Although several methods are available for estimating the duration of the cell cycle, it is difficult to determinate small differences of TC between two different cell populations due to biological and/or experimental variability. A novel strategy based in co-cultivation of two cell strains followed by a series of dilution and propagation of the culture will allow the quantification of very small differences in the length of two cell populations at resolution levels not possible at present with current methods. This is achieved by a separation of the endpoint variable measured to compare between two cell populations. The theoretical basis of this approach is discussed in the context of published experimental data and simulation of idealized experiments using virtual strains of different cell cycle length.

scholarly journals Replication fork rate and origin activation during the S phase of Saccharomyces cerevisiae.

1980 ◽  
Vol 85 (1) ◽  
pp. 108-115 ◽  
Author(s):  
C J Rivin ◽  
W L Fangman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cycle Length ◽  
Replication Fork ◽  
Nitrogen Sources ◽  
S Phase ◽  
Phase Duration ◽  
Yeast Saccharomyces Cerevisiae ◽  
Origin Activation ◽  
Cell Cycle Length

When the growth rate of the yeast Saccharomyces cerevisiae is limited with various nitrogen sources, the duration of the S phase is proportional to cell cycle length over a fourfold range of growth rates (C.J. Rivin and W. L. Fangman, 1980, J. Cell Biol. 85:96-107). Molecular parameters of the S phases of these cells were examined by DNA fiber autoradiography. Changes in replication fork rate account completely for the changes in S-phase duration. No changes in origin-to-origin distances were detected. In addition, it was found that while most adjacent replication origins are activated within a few minutes of each other, new activations occur throughout the S phase.

435 REDUCTION OF CELL CYCLE LENGTH AND INCREASE IN S-PHASE BY GROWTH FACTORS IN PIG FETAL FIBROBLASTS

2010 ◽  
Vol 22 (1) ◽  
pp. 374
Author(s):  
S. Waghmare ◽  
B. Mir
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Growth Factors ◽  
Growth Factor ◽  
Cycle Length ◽  
S Phase ◽  
Proliferation Rate ◽  
Fetal Fibroblasts ◽  
Cell Cycle Length ◽  
Number Of Cells

Gene targeting in primary somatic cells is inefficient compared with embryonic stem cells. This is because of a slow rate of cell proliferation, fewer cells in S-phase at a given time point under normal culture conditions, and low rate of homologous recombination. Homologous recombination occurs mainly in late S-phase and increase in gene targeting efficiency has been reported in S-phase synchronized cells in bovine and rhesus macaque fetal fibroblasts. In this study we tested several growth factors: platelet-derived growth factor (PDGF), tumor necrosis factor a (TNFα), epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor β1 (TGFβ1), insulin-like growth factor 1 (ILGF-1) and insulin-like growth factor II (ILGF-II) individually and in various combinations to see the effect on cell proliferation rate. Each experimental set consisted of 3 replicates. TGFβ1-, ILGF1-, ILGFII-, and FGF-treated cells grew very slowly compared with untreated cells. However, a combination of 3 growth factors: PDGF (15 ng mL-1), EGF (50 ng mL-1) and TNFa (100 pg mL-1), herein referred to as the cocktail, accelerated cell proliferation rate and reduced cell cycle length on average from 24.5 ± 0.2 to 20.4 ± 0.5 h with no significant change in number of cells in S-phase. Further, cells grown in the presence of the cocktail showed changes in morphology. The cells became spindle-shaped and occupied less surface area per cell compared with untreated cells. Importantly, cocktail-treated cells maintained a normal karyotype without any chromosomal abnormality. Thymidine has been used successfully to block various cell types in S-phase but it failed to synchronize these cells in S-phase in the concentration range of 2 to 10 mM for 24 to 48 h. However, serum starvation (0.2% fetal bovine serum) for 48 h blocked the cell proliferation rate effectively and synchronized cells in G0 phase (80-82% cells). After releasing from the block, cells were grown in the absence or presence of cocktail and cell cycle analysis was done at different time points by flow cytometry. Each time point was repeated 3 times. We observed the maximum number of cells in S-phase at 22 to 23 h (61.33% ± 7.77 in cocktail-treated cells v. 41.7% ± 3.28 in untreated cells). In summary, the cocktail-treated cells showed changes in cell morphology, higher proliferation rate, reduction in cell cycle length by 16.7%, and maximum percentage of cells in S-phase following serum starvation but maintained normal karyotypes. This high proliferation rate, reduction in cell cycle length, and maximum number of cells in S-phase should be very helpful in increasing the efficiency of gene-targeting in pig fetal fibroblasts.

scholarly journals MicroRNA 22 Regulates Cell Cycle Length in Cerebellar Granular Neuron Precursors

2013 ◽  
Vol 33 (14) ◽  
pp. 2706-2717 ◽  
Author(s):  
J. Berenguer ◽  
A. Herrera ◽  
L. Vuolo ◽  
B. Torroba ◽  
F. Llorens ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cycle Length ◽  
Cell Cycle Length
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