PUBLICATION
A spatio-temporal model of notch signalling in the zebrafish segmentation clock: conditions for synchronised oscillatory dynamics
- Authors
- Terry, A.J., Sturrock, M., Dale, J.K., Maroto, M., and Chaplain, M.A.
- ID
- ZDB-PUB-110324-2
- Date
- 2011
- Source
- PLoS One 6(2): e16980 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Basic Helix-Loop-Helix Transcription Factors/genetics
- Basic Helix-Loop-Helix Transcription Factors/physiology
- Biological Clocks/genetics
- Biological Clocks/physiology*
- Body Patterning/genetics
- Cleavage Stage, Ovum/metabolism*
- Cleavage Stage, Ovum/physiology
- Computer Simulation
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/physiology
- Models, Biological
- Models, Theoretical*
- Morphogenesis/genetics
- Morphogenesis/physiology
- Receptors, Notch/genetics
- Receptors, Notch/metabolism*
- Receptors, Notch/physiology
- Signal Transduction/genetics
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology
- PubMed
- 21386903 Full text @ PLoS One
Citation
Terry, A.J., Sturrock, M., Dale, J.K., Maroto, M., and Chaplain, M.A. (2011) A spatio-temporal model of notch signalling in the zebrafish segmentation clock: conditions for synchronised oscillatory dynamics. PLoS One. 6(2):e16980.
Abstract
In the vertebrate embryo, tissue blocks called somites are laid down in head-to-tail succession, a process known as somitogenesis. Research into somitogenesis has been both experimental and mathematical. For zebrafish, there is experimental evidence for oscillatory gene expression in cells in the presomitic mesoderm (PSM) as well as evidence that Notch signalling synchronises the oscillations in neighbouring PSM cells. A biological mechanism has previously been proposed to explain these phenomena. Here we have converted this mechanism into a mathematical model of partial differential equations in which the nuclear and cytoplasmic diffusion of protein and mRNA molecules is explictly considered. By performing simulations, we have found ranges of values for the model parameters (such as diffusion and degradation rates) that yield oscillatory dynamics within PSM cells and that enable Notch signalling to synchronise the oscillations in two touching cells. Our model contains a Hill coefficient that measures the co-operativity between two proteins (Her1, Her7) and three genes (her1, her7, deltaC) which they inhibit. This coefficient appears to be bounded below by the requirement for oscillations in individual cells and bounded above by the requirement for synchronisation. Consistent with experimental data and a previous spatially non-explicit mathematical model, we have found that signalling can increase the average level of Her1 protein. Biological pattern formation would be impossible without a certain robustness to variety in cell shape and size; our results possess such robustness. Our spatially-explicit modelling approach, together with new imaging technologies that can measure intracellular protein diffusion rates, is likely to yield significant new insight into somitogenesis and other biological processes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping