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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

Gene expression parameter sensitivity analysis.(a-d) A 10% change in dl-sog threshold, θdl:sog (a,b), or noise parameter, η (c,d), causes a greater difference in the total dl case than the free dl only case. (e-h) In the same way, a 10% change in dl-zen threshold, θdl:zen (e,f), or noise parameter (g,h) causes a greater difference to the total dl case than the free dl case. For each case, sensitivity was analyzed using the best parameter set for η = 0.2, and each line shown is the average of 10 simulations. The data to which the model was optimized are shown as dotted lines. (Note: each run is an average of 10 runs for each parameter set to reduce randomness in the plot due to noise.)
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pcbi.1004159.g006: Gene expression parameter sensitivity analysis.(a-d) A 10% change in dl-sog threshold, θdl:sog (a,b), or noise parameter, η (c,d), causes a greater difference in the total dl case than the free dl only case. (e-h) In the same way, a 10% change in dl-zen threshold, θdl:zen (e,f), or noise parameter (g,h) causes a greater difference to the total dl case than the free dl case. For each case, sensitivity was analyzed using the best parameter set for η = 0.2, and each line shown is the average of 10 simulations. The data to which the model was optimized are shown as dotted lines. (Note: each run is an average of 10 runs for each parameter set to reduce randomness in the plot due to noise.)

Mentions: The model with free dl is insensitive to 10% variations in the three model parameters (θdl:mRNA, τmRNA, η) for each gene tested (Fig. 6). In contrast, the Type III genes in the model using total dl are highly sensitive to the value of θdl:mRNA as well as η. This result emphasizes that our understanding of how the dl gradient specifies genes far away from the ventral midline is contingent on the proper interpretation of dl fluorescence measurements.


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)

Gene expression parameter sensitivity analysis.(a-d) A 10% change in dl-sog threshold, θdl:sog (a,b), or noise parameter, η (c,d), causes a greater difference in the total dl case than the free dl only case. (e-h) In the same way, a 10% change in dl-zen threshold, θdl:zen (e,f), or noise parameter (g,h) causes a greater difference to the total dl case than the free dl case. For each case, sensitivity was analyzed using the best parameter set for η = 0.2, and each line shown is the average of 10 simulations. The data to which the model was optimized are shown as dotted lines. (Note: each run is an average of 10 runs for each parameter set to reduce randomness in the plot due to noise.)
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004159.g006: Gene expression parameter sensitivity analysis.(a-d) A 10% change in dl-sog threshold, θdl:sog (a,b), or noise parameter, η (c,d), causes a greater difference in the total dl case than the free dl only case. (e-h) In the same way, a 10% change in dl-zen threshold, θdl:zen (e,f), or noise parameter (g,h) causes a greater difference to the total dl case than the free dl case. For each case, sensitivity was analyzed using the best parameter set for η = 0.2, and each line shown is the average of 10 simulations. The data to which the model was optimized are shown as dotted lines. (Note: each run is an average of 10 runs for each parameter set to reduce randomness in the plot due to noise.)
Mentions: The model with free dl is insensitive to 10% variations in the three model parameters (θdl:mRNA, τmRNA, η) for each gene tested (Fig. 6). In contrast, the Type III genes in the model using total dl are highly sensitive to the value of θdl:mRNA as well as η. This result emphasizes that our understanding of how the dl gradient specifies genes far away from the ventral midline is contingent on the proper interpretation of dl fluorescence measurements.

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