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The presence of nuclear cactus in the early Drosophila embryo may extend the dynamic range of the dorsal gradient.

O'Connell MD, Reeves GT - PLoS Comput. Biol. (2015)

Bottom Line: We found that two assumptions are required for the model to match experimental data in both Dorsal distribution and gene expression patterns.And second, we assume that fluorescence measurements of Dorsal reflect both free Dorsal and Cactus-bound Dorsal.Our results have a general implication for interpreting fluorescence-based measurements of signaling molecules.

View Article: PubMed Central - PubMed

Affiliation: North Carolina State University Department of Chemical and Biomolecular Engineering, Raleigh, North Carolina, United States of America.

ABSTRACT
In a developing embryo, the spatial distribution of a signaling molecule, or a morphogen gradient, has been hypothesized to carry positional information to pattern tissues. Recent measurements of morphogen distribution have allowed us to subject this hypothesis to rigorous physical testing. In the early Drosophila embryo, measurements of the morphogen Dorsal, which is a transcription factor responsible for initiating the earliest zygotic patterns along the dorsal-ventral axis, have revealed a gradient that is too narrow to pattern the entire axis. In this study, we use a mathematical model of Dorsal dynamics, fit to experimental data, to determine the ability of the Dorsal gradient to regulate gene expression across the entire dorsal-ventral axis. We found that two assumptions are required for the model to match experimental data in both Dorsal distribution and gene expression patterns. First, we assume that Cactus, an inhibitor that binds to Dorsal and prevents it from entering the nuclei, must itself be present in the nuclei. And second, we assume that fluorescence measurements of Dorsal reflect both free Dorsal and Cactus-bound Dorsal. Our model explains the dynamic behavior of the Dorsal gradient at lateral and dorsal positions of the embryo, the ability of Dorsal to regulate gene expression across the entire dorsal-ventral axis, and the robustness of gene expression to stochastic effects. Our results have a general implication for interpreting fluorescence-based measurements of signaling molecules.

No MeSH data available.


Related in: MedlinePlus

Import/export parameter analysis.(a,c,e) Scatter plot of logarithms of nuclear export vs import rates for dl (a), dl/Cact (c) and Cact (e). Each point is a weighted mean of the 100 parameter sets from a single evolutionary optimization run, with error bars representing the weighted standard deviation for those parameter sets. Color indicates weighted median RSS error for each set. (b,d,f) Equilibrium constant distributions: logarithms of quotients of all import/export parameter values (ζi and ξi, respectively).
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pcbi.1004159.g004: Import/export parameter analysis.(a,c,e) Scatter plot of logarithms of nuclear export vs import rates for dl (a), dl/Cact (c) and Cact (e). Each point is a weighted mean of the 100 parameter sets from a single evolutionary optimization run, with error bars representing the weighted standard deviation for those parameter sets. Color indicates weighted median RSS error for each set. (b,d,f) Equilibrium constant distributions: logarithms of quotients of all import/export parameter values (ζi and ξi, respectively).

Mentions: Both the import and the export rates of dl largely cluster in a small region of parameter space (Fig. 4a). Deviations from this cluster are highly correlated between these two parameters, with a sparse, high-RSS-error tail. Thus, the nuclear import equilibrium constant (the ratio of import to export) for dl is largely contained within one order of magnitude and, perhaps unsurprisingly, favors import (Fig. 4b).


The presence of nuclear cactus in the early Drosophila embryo may extend the dynamic range of the dorsal gradient.

O'Connell MD, Reeves GT - PLoS Comput. Biol. (2015)

Import/export parameter analysis.(a,c,e) Scatter plot of logarithms of nuclear export vs import rates for dl (a), dl/Cact (c) and Cact (e). Each point is a weighted mean of the 100 parameter sets from a single evolutionary optimization run, with error bars representing the weighted standard deviation for those parameter sets. Color indicates weighted median RSS error for each set. (b,d,f) Equilibrium constant distributions: logarithms of quotients of all import/export parameter values (ζi and ξi, respectively).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400154&req=5

pcbi.1004159.g004: Import/export parameter analysis.(a,c,e) Scatter plot of logarithms of nuclear export vs import rates for dl (a), dl/Cact (c) and Cact (e). Each point is a weighted mean of the 100 parameter sets from a single evolutionary optimization run, with error bars representing the weighted standard deviation for those parameter sets. Color indicates weighted median RSS error for each set. (b,d,f) Equilibrium constant distributions: logarithms of quotients of all import/export parameter values (ζi and ξi, respectively).
Mentions: Both the import and the export rates of dl largely cluster in a small region of parameter space (Fig. 4a). Deviations from this cluster are highly correlated between these two parameters, with a sparse, high-RSS-error tail. Thus, the nuclear import equilibrium constant (the ratio of import to export) for dl is largely contained within one order of magnitude and, perhaps unsurprisingly, favors import (Fig. 4b).

Bottom Line: We found that two assumptions are required for the model to match experimental data in both Dorsal distribution and gene expression patterns.And second, we assume that fluorescence measurements of Dorsal reflect both free Dorsal and Cactus-bound Dorsal.Our results have a general implication for interpreting fluorescence-based measurements of signaling molecules.

View Article: PubMed Central - PubMed

Affiliation: North Carolina State University Department of Chemical and Biomolecular Engineering, Raleigh, North Carolina, United States of America.

ABSTRACT
In a developing embryo, the spatial distribution of a signaling molecule, or a morphogen gradient, has been hypothesized to carry positional information to pattern tissues. Recent measurements of morphogen distribution have allowed us to subject this hypothesis to rigorous physical testing. In the early Drosophila embryo, measurements of the morphogen Dorsal, which is a transcription factor responsible for initiating the earliest zygotic patterns along the dorsal-ventral axis, have revealed a gradient that is too narrow to pattern the entire axis. In this study, we use a mathematical model of Dorsal dynamics, fit to experimental data, to determine the ability of the Dorsal gradient to regulate gene expression across the entire dorsal-ventral axis. We found that two assumptions are required for the model to match experimental data in both Dorsal distribution and gene expression patterns. First, we assume that Cactus, an inhibitor that binds to Dorsal and prevents it from entering the nuclei, must itself be present in the nuclei. And second, we assume that fluorescence measurements of Dorsal reflect both free Dorsal and Cactus-bound Dorsal. Our model explains the dynamic behavior of the Dorsal gradient at lateral and dorsal positions of the embryo, the ability of Dorsal to regulate gene expression across the entire dorsal-ventral axis, and the robustness of gene expression to stochastic effects. Our results have a general implication for interpreting fluorescence-based measurements of signaling molecules.

No MeSH data available.


Related in: MedlinePlus