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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 simulations.(a, b) Using the free (active) dl gradient, we were able to accurately simulate the gene expression patterns measured with FISH [10]. (c, d) Using the total dl gradient, we obtain poor fits to Type III genes (sog, zen), as was expected. In (b, d) the fuchsia curve indicates the active dl gradient at the end of NC14, plotted on a log scale. Horizontal lines indicate median threshold parameter values, and vertical dotted lines indicate where in the DV axis we expect the final expression borders of each gene, according to where the gradient crosses the threshold. Note that the zen threshold is below the NC14 gradient in the total dl case (c, d), and that zen expression is thus a result of noise. (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.g005: Gene expression simulations.(a, b) Using the free (active) dl gradient, we were able to accurately simulate the gene expression patterns measured with FISH [10]. (c, d) Using the total dl gradient, we obtain poor fits to Type III genes (sog, zen), as was expected. In (b, d) the fuchsia curve indicates the active dl gradient at the end of NC14, plotted on a log scale. Horizontal lines indicate median threshold parameter values, and vertical dotted lines indicate where in the DV axis we expect the final expression borders of each gene, according to where the gradient crosses the threshold. Note that the zen threshold is below the NC14 gradient in the total dl case (c, d), and that zen expression is thus a result of noise. (Note: each run is an average of 10 runs for each parameter set to reduce randomness in the plot due to noise.)

Mentions: Using evolutionary optimization, we found parameter sets that show excellent agreement with the fluorescence in situ hybridization (FISH) data for sna, vnd, sog, and zen (Fig. 5a). In particular, our results indicate that the dl nuclear gradient can indeed pattern Type III genes, perhaps due to the fact that the nuclear concentration of free (active) dl drops by another order of magnitude past 40% DV axis (Fig. 5b), in constrast to total dl, which drops by only 20% in the same range (Fig. 5d). As shown in Fig. 5b, the gene expression thresholds cross the NC14 dl gradient at about the same location as the half-max of the corresponding gene’s boundary.


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 simulations.(a, b) Using the free (active) dl gradient, we were able to accurately simulate the gene expression patterns measured with FISH [10]. (c, d) Using the total dl gradient, we obtain poor fits to Type III genes (sog, zen), as was expected. In (b, d) the fuchsia curve indicates the active dl gradient at the end of NC14, plotted on a log scale. Horizontal lines indicate median threshold parameter values, and vertical dotted lines indicate where in the DV axis we expect the final expression borders of each gene, according to where the gradient crosses the threshold. Note that the zen threshold is below the NC14 gradient in the total dl case (c, d), and that zen expression is thus a result of noise. (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

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

pcbi.1004159.g005: Gene expression simulations.(a, b) Using the free (active) dl gradient, we were able to accurately simulate the gene expression patterns measured with FISH [10]. (c, d) Using the total dl gradient, we obtain poor fits to Type III genes (sog, zen), as was expected. In (b, d) the fuchsia curve indicates the active dl gradient at the end of NC14, plotted on a log scale. Horizontal lines indicate median threshold parameter values, and vertical dotted lines indicate where in the DV axis we expect the final expression borders of each gene, according to where the gradient crosses the threshold. Note that the zen threshold is below the NC14 gradient in the total dl case (c, d), and that zen expression is thus a result of noise. (Note: each run is an average of 10 runs for each parameter set to reduce randomness in the plot due to noise.)
Mentions: Using evolutionary optimization, we found parameter sets that show excellent agreement with the fluorescence in situ hybridization (FISH) data for sna, vnd, sog, and zen (Fig. 5a). In particular, our results indicate that the dl nuclear gradient can indeed pattern Type III genes, perhaps due to the fact that the nuclear concentration of free (active) dl drops by another order of magnitude past 40% DV axis (Fig. 5b), in constrast to total dl, which drops by only 20% in the same range (Fig. 5d). As shown in Fig. 5b, the gene expression thresholds cross the NC14 dl gradient at about the same location as the half-max of the corresponding gene’s boundary.

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