Limits...
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 without nuclear dl/Cact.(a) Simulations of the model assuming nuclei begin interphase empty and that only free cytoplasmic dl is imported into the nucleus. (b) 3D surface plot of the best-fit parameter set. (c) Snapshots of the end of each nuclear cycle according to this model. (d) Same as in (c), normalized.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4400154&req=5

pcbi.1004159.g002: Model results without nuclear dl/Cact.(a) Simulations of the model assuming nuclei begin interphase empty and that only free cytoplasmic dl is imported into the nucleus. (b) 3D surface plot of the best-fit parameter set. (c) Snapshots of the end of each nuclear cycle according to this model. (d) Same as in (c), normalized.

Mentions: The following description is for the full model that includes dl/Cact complex and Cact in the nuclei. (For a description of the initial model used—depicted in Fig. 2—see S1 Text.) During interphase, the nuclear and cytoplasmic concentrations are governed by the parameters associated with nuclear import/export, intercompartmental exchange, production/degradation of Cact, and binding/unbinding of dl/Cact complex. At the start of mitosis the nuclei break down and the contents of each nucleus are mixed with that of the surrounding cytoplasmic compartments (Fig. 1c, center panel). The equations for the mitosis phase are subsequently solved for the appropriate duration, and the next interphase begins with nuclei and cytoplasmic compartments having the same concentration (Fig. 1c, right panel). This allows for the presence of all three molecular species (dl, Cact and dl/Cact complex) to exist in the nuclei at the start of interphase.


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 without nuclear dl/Cact.(a) Simulations of the model assuming nuclei begin interphase empty and that only free cytoplasmic dl is imported into the nucleus. (b) 3D surface plot of the best-fit parameter set. (c) Snapshots of the end of each nuclear cycle according to this model. (d) Same as in (c), normalized.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi.1004159.g002: Model results without nuclear dl/Cact.(a) Simulations of the model assuming nuclei begin interphase empty and that only free cytoplasmic dl is imported into the nucleus. (b) 3D surface plot of the best-fit parameter set. (c) Snapshots of the end of each nuclear cycle according to this model. (d) Same as in (c), normalized.
Mentions: The following description is for the full model that includes dl/Cact complex and Cact in the nuclei. (For a description of the initial model used—depicted in Fig. 2—see S1 Text.) During interphase, the nuclear and cytoplasmic concentrations are governed by the parameters associated with nuclear import/export, intercompartmental exchange, production/degradation of Cact, and binding/unbinding of dl/Cact complex. At the start of mitosis the nuclei break down and the contents of each nucleus are mixed with that of the surrounding cytoplasmic compartments (Fig. 1c, center panel). The equations for the mitosis phase are subsequently solved for the appropriate duration, and the next interphase begins with nuclei and cytoplasmic compartments having the same concentration (Fig. 1c, right panel). This allows for the presence of all three molecular species (dl, Cact and dl/Cact complex) to exist in the nuclei at the start of interphase.

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