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Oscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach

Geneviève Dupont, Elke Heytens UGent and Luc Leybaert UGent (2010) INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY. 54(4). p.655-665
abstract
Fertilization in mammals is accompanied by Ca2+ oscillations in the egg cytoplasm, leading to exit from meiosis and entry into the first embryonic cell cycle. The signal transduction pathway linking these Ca2+ changes to cell-cycle related kinases has not yet been fully elucidated, but involves activation of calmodulin-dependent kinase II (CaMKII). Here, we develop a computational model to investigate the mechanism by which cell cycle resumption can be sensitive to the temporal pattern of Ca2+ increases. Using a model for CaMKII activation that reproduces the frequency sensitivity of this kinase, simulations confirm that Ca2+ spikes are accompanied by in phase variations in the level of CaMKII activity and suggest that in most mammalian species, Ca2+ spikes are well suited to maximize CaMKII activation. The full model assumes that CaMKII brings about a decrease in the level of cyclinB-cdk1 by two pathways, only one of which is CSF-dependent. Parameters are selected to account for the experimental observations where mouse eggs were artificially activated by different Ca2+ stimulatory protocols. The model is then used in the context of 'assisted oocyte activation (AOA)' to investigate why the best rates of successful activation are obtained when eggs are submitted to two applications of Ca2+ ionophores.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
in vitro fertilization, CaMKII, calcium ionophore, assisted oocyte activation (AOA), DEPENDENT PROTEIN-KINASE, INTRACYTOPLASMIC SPERM INJECTION, EGG ACTIVATION, EMBRYO DEVELOPMENT, OOCYTE ACTIVATION, CALCIUM OSCILLATIONS, MOUSE OOCYTES, MEIOSIS-II, PLC-ZETA, CALMODULIN
journal title
INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY
Int. J. Dev. Biol.
volume
54
issue
4
pages
655 - 665
Web of Science type
Article
Web of Science id
000277128600012
JCR category
DEVELOPMENTAL BIOLOGY
JCR impact factor
2.856 (2010)
JCR rank
18/38 (2010)
JCR quartile
2 (2010)
ISSN
0214-6282
DOI
10.1387/ijdb.082845gd
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
829039
handle
http://hdl.handle.net/1854/LU-829039
date created
2010-01-15 19:42:16
date last changed
2010-06-25 16:23:19
@article{829039,
  abstract     = {Fertilization in mammals is accompanied by Ca2+ oscillations in the egg cytoplasm, leading to exit from meiosis and entry into the first embryonic cell cycle. The signal transduction pathway linking these Ca2+ changes to cell-cycle related kinases has not yet been fully elucidated, but involves activation of calmodulin-dependent kinase II (CaMKII). Here, we develop a computational model to investigate the mechanism by which cell cycle resumption can be sensitive to the temporal pattern of Ca2+ increases. Using a model for CaMKII activation that reproduces the frequency sensitivity of this kinase, simulations confirm that Ca2+ spikes are accompanied by in phase variations in the level of CaMKII activity and suggest that in most mammalian species, Ca2+ spikes are well suited to maximize CaMKII activation. The full model assumes that CaMKII brings about a decrease in the level of cyclinB-cdk1 by two pathways, only one of which is CSF-dependent. Parameters are selected to account for the experimental observations where mouse eggs were artificially activated by different Ca2+ stimulatory protocols. The model is then used in the context of 'assisted oocyte activation (AOA)' to investigate why the best rates of successful activation are obtained when eggs are submitted to two applications of Ca2+ ionophores.},
  author       = {Dupont, Genevi{\`e}ve and Heytens, Elke and Leybaert, Luc},
  issn         = {0214-6282},
  journal      = {INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY},
  keyword      = {in vitro fertilization,CaMKII,calcium ionophore,assisted oocyte activation (AOA),DEPENDENT PROTEIN-KINASE,INTRACYTOPLASMIC SPERM INJECTION,EGG ACTIVATION,EMBRYO DEVELOPMENT,OOCYTE ACTIVATION,CALCIUM OSCILLATIONS,MOUSE OOCYTES,MEIOSIS-II,PLC-ZETA,CALMODULIN},
  language     = {eng},
  number       = {4},
  pages        = {655--665},
  title        = {Oscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach},
  url          = {http://dx.doi.org/10.1387/ijdb.082845gd},
  volume       = {54},
  year         = {2010},
}

Chicago
Dupont, Geneviève, Elke Heytens, and Luc Leybaert. 2010. “Oscillatory Ca2+ Dynamics and Cell Cycle Resumption at Fertilization in Mammals: a Modelling Approach.” International Journal of Developmental Biology 54 (4): 655–665.
APA
Dupont, Geneviève, Heytens, E., & Leybaert, L. (2010). Oscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach. INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 54(4), 655–665.
Vancouver
1.
Dupont G, Heytens E, Leybaert L. Oscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach. INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY. 2010;54(4):655–65.
MLA
Dupont, Geneviève, Elke Heytens, and Luc Leybaert. “Oscillatory Ca2+ Dynamics and Cell Cycle Resumption at Fertilization in Mammals: a Modelling Approach.” INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY 54.4 (2010): 655–665. Print.