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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

Model results with nuclear dl/Cact.(a) Surface plot of the best-fit parameter set (Unuc + Wnuc). (b) Surface plot of nuclear free dl (Unuc, Equation 1). (c) Surface plot of nuclear dl/Cact complex (Wnuc, Equation 3). (d) The best-fit simulation result compared to the nuclear dl-Venus data from [10], normalized to dl-Venus maximum. Width refers to σ value when fit to a Gaussian function; dotted line represents average dl gradient width of 0.15 as in [10]. (e) Comparing snapshots at the end of each nuclear cycle. (f) Comparison of NC14 gradient snapshots.
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pcbi.1004159.g003: Model results with nuclear dl/Cact.(a) Surface plot of the best-fit parameter set (Unuc + Wnuc). (b) Surface plot of nuclear free dl (Unuc, Equation 1). (c) Surface plot of nuclear dl/Cact complex (Wnuc, Equation 3). (d) The best-fit simulation result compared to the nuclear dl-Venus data from [10], normalized to dl-Venus maximum. Width refers to σ value when fit to a Gaussian function; dotted line represents average dl gradient width of 0.15 as in [10]. (e) Comparing snapshots at the end of each nuclear cycle. (f) Comparison of NC14 gradient snapshots.

Mentions: Our modeling results largely agreed with previously published observations. Specifically, we were able to simulate the overall increase in nuclear dl seen along the ventral midline (Fig. 2a), and the overall spatiotemporal shape of the simulated data set was in qualitative agreement with the dl-Venus data set (Fig. 2b; compare with Fig. 3a). However, our model could not simulate the decrease in nuclear dl seen in the dorsal-most nuclei (see Fig. 2a).


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)

Model results with nuclear dl/Cact.(a) Surface plot of the best-fit parameter set (Unuc + Wnuc). (b) Surface plot of nuclear free dl (Unuc, Equation 1). (c) Surface plot of nuclear dl/Cact complex (Wnuc, Equation 3). (d) The best-fit simulation result compared to the nuclear dl-Venus data from [10], normalized to dl-Venus maximum. Width refers to σ value when fit to a Gaussian function; dotted line represents average dl gradient width of 0.15 as in [10]. (e) Comparing snapshots at the end of each nuclear cycle. (f) Comparison of NC14 gradient snapshots.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004159.g003: Model results with nuclear dl/Cact.(a) Surface plot of the best-fit parameter set (Unuc + Wnuc). (b) Surface plot of nuclear free dl (Unuc, Equation 1). (c) Surface plot of nuclear dl/Cact complex (Wnuc, Equation 3). (d) The best-fit simulation result compared to the nuclear dl-Venus data from [10], normalized to dl-Venus maximum. Width refers to σ value when fit to a Gaussian function; dotted line represents average dl gradient width of 0.15 as in [10]. (e) Comparing snapshots at the end of each nuclear cycle. (f) Comparison of NC14 gradient snapshots.
Mentions: Our modeling results largely agreed with previously published observations. Specifically, we were able to simulate the overall increase in nuclear dl seen along the ventral midline (Fig. 2a), and the overall spatiotemporal shape of the simulated data set was in qualitative agreement with the dl-Venus data set (Fig. 2b; compare with Fig. 3a). However, our model could not simulate the decrease in nuclear dl seen in the dorsal-most nuclei (see Fig. 2a).

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