Limits...
A spatio-temporal model of Notch signalling in the zebrafish segmentation clock: conditions for synchronised oscillatory dynamics.

Terry AJ, Sturrock M, Dale JK, Maroto M, Chaplain MA - PLoS ONE (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Mathematics, University of Dundee, Dundee, United Kingdom. aterry@maths.dundee.ac.uk

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 explicitly 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.

Show MeSH
Notch signalling model simulation results showing spatial distributions of Her1 protein.The plots show Her1 protein concentration at 100 minute intervals. The concentration is scaled by a reference value (multiplying the concentration by  gives the true concentration). The parameters used to create the middle plot in figure 7 are used here (see Supporting Information). Signalling between the cells begins at 150 minutes and has clearly synchronised their behaviour by 600 minutes.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3046134&req=5

pone-0016980-g009: Notch signalling model simulation results showing spatial distributions of Her1 protein.The plots show Her1 protein concentration at 100 minute intervals. The concentration is scaled by a reference value (multiplying the concentration by gives the true concentration). The parameters used to create the middle plot in figure 7 are used here (see Supporting Information). Signalling between the cells begins at 150 minutes and has clearly synchronised their behaviour by 600 minutes.

Mentions: Simulations for our signalling model, performed on hexagonal cells with circular nuclei, are demonstrated in figures 7, 8, 9, 10, 11, and 12, and also in two Supporting Information files (see “Animation S3” and “Animation S4”). We denote as cells 1 and 2 the cells that are on the left and right respectively in figures 8, 9, 11, and 12.


A spatio-temporal model of Notch signalling in the zebrafish segmentation clock: conditions for synchronised oscillatory dynamics.

Terry AJ, Sturrock M, Dale JK, Maroto M, Chaplain MA - PLoS ONE (2011)

Notch signalling model simulation results showing spatial distributions of Her1 protein.The plots show Her1 protein concentration at 100 minute intervals. The concentration is scaled by a reference value (multiplying the concentration by  gives the true concentration). The parameters used to create the middle plot in figure 7 are used here (see Supporting Information). Signalling between the cells begins at 150 minutes and has clearly synchronised their behaviour by 600 minutes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046134&req=5

pone-0016980-g009: Notch signalling model simulation results showing spatial distributions of Her1 protein.The plots show Her1 protein concentration at 100 minute intervals. The concentration is scaled by a reference value (multiplying the concentration by gives the true concentration). The parameters used to create the middle plot in figure 7 are used here (see Supporting Information). Signalling between the cells begins at 150 minutes and has clearly synchronised their behaviour by 600 minutes.
Mentions: Simulations for our signalling model, performed on hexagonal cells with circular nuclei, are demonstrated in figures 7, 8, 9, 10, 11, and 12, and also in two Supporting Information files (see “Animation S3” and “Animation S4”). We denote as cells 1 and 2 the cells that are on the left and right respectively in figures 8, 9, 11, and 12.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Mathematics, University of Dundee, Dundee, United Kingdom. aterry@maths.dundee.ac.uk

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 explicitly 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.

Show MeSH