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Microtubules provide directional information for core PCP function.

Matis M, Russler-Germain DA, Hu Q, Tomlin CJ, Axelrod JD - Elife (2014)

Bottom Line: Consistent with previous results, we find that the Ft/Ds/Fj-module has an effect on a MT-cytoskeleton.We show Ft/Ds/Fj-dependent initial polarization of the apical MT-cytoskeleton prior to global alignment of the core-module, reveal that the anchoring of apical non-centrosomal MTs at apical junctions is polarized, observe that directional trafficking of vesicles containing Dsh depends on Ft, and demonstrate the feasibility of this model by mathematical simulation.Together, these results support the hypothesis that Ft/Ds/Fj provides a signal to orient core PCP function via MT polarization.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, United States matism@uni-muenster.de.

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Simulation results.Simulations of clones of fz (A), dsh (B) and ft (C)  clones validating that the mathematical model captures the domineering non-autonomy phenotypes as well as the ability of the core system to propagate through ft mutant tissue. The color scale represents the magnitude of the vector sum of Dsh in each cell. The length of the hair and its distance from the center of the cell is also plotted proportionally to the vector sum of Dsh in each cell. (D) A 6 × 30 cell grid used to simulate polarization kinetics. Cells with kinetics plotted in Figure 5 are marked with asterisks. Greyscales represent the combined quantity of Dsh on either side of each shared cell boundary, as would be seen with light microscopy.DOI:http://dx.doi.org/10.7554/eLife.02893.023
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fig5s1: Simulation results.Simulations of clones of fz (A), dsh (B) and ft (C) clones validating that the mathematical model captures the domineering non-autonomy phenotypes as well as the ability of the core system to propagate through ft mutant tissue. The color scale represents the magnitude of the vector sum of Dsh in each cell. The length of the hair and its distance from the center of the cell is also plotted proportionally to the vector sum of Dsh in each cell. (D) A 6 × 30 cell grid used to simulate polarization kinetics. Cells with kinetics plotted in Figure 5 are marked with asterisks. Greyscales represent the combined quantity of Dsh on either side of each shared cell boundary, as would be seen with light microscopy.DOI:http://dx.doi.org/10.7554/eLife.02893.023

Mentions: Our results thus far suggest that gradients of Ds and Fj expression, by producing asymmetric orientation of Ft-Ds heterodimers, provide directional information to bias core protein polarization. Given the apparent variation in asymmetry of Ft-Ds dimers at different times and places in wing development, we wished to assess the potential consequences of this variation on core PCP protein asymmetry. We therefore simulated this mechanism by adapting our previously described mathematical model for PCP signaling (Amonlirdviman et al., 2005; Ma et al., 2008). The modified model establishes a MT network with polarity determined by the relative concentrations of Ft on any side of a cell. User-defined input gradients of Ds and Fj determine Ft concentrations in a manner consistent with the experimentally defined model. Dsh is then transported toward the plus ends of MTs, while still permitting bulk movement of all components by diffusion (see Supplementary file 1). We first validated the model by correctly reproducing the domineering non-autonomy (or lack thereof) surrounding clones of core PCP mutants (Figure 5—figure supplement 1). Furthermore, we confirmed that the model correctly simulates the ability of the core module to propagate polarization across small ft mutant clones (Figure 5—figure supplement 1).


Microtubules provide directional information for core PCP function.

Matis M, Russler-Germain DA, Hu Q, Tomlin CJ, Axelrod JD - Elife (2014)

Simulation results.Simulations of clones of fz (A), dsh (B) and ft (C)  clones validating that the mathematical model captures the domineering non-autonomy phenotypes as well as the ability of the core system to propagate through ft mutant tissue. The color scale represents the magnitude of the vector sum of Dsh in each cell. The length of the hair and its distance from the center of the cell is also plotted proportionally to the vector sum of Dsh in each cell. (D) A 6 × 30 cell grid used to simulate polarization kinetics. Cells with kinetics plotted in Figure 5 are marked with asterisks. Greyscales represent the combined quantity of Dsh on either side of each shared cell boundary, as would be seen with light microscopy.DOI:http://dx.doi.org/10.7554/eLife.02893.023
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4151085&req=5

fig5s1: Simulation results.Simulations of clones of fz (A), dsh (B) and ft (C) clones validating that the mathematical model captures the domineering non-autonomy phenotypes as well as the ability of the core system to propagate through ft mutant tissue. The color scale represents the magnitude of the vector sum of Dsh in each cell. The length of the hair and its distance from the center of the cell is also plotted proportionally to the vector sum of Dsh in each cell. (D) A 6 × 30 cell grid used to simulate polarization kinetics. Cells with kinetics plotted in Figure 5 are marked with asterisks. Greyscales represent the combined quantity of Dsh on either side of each shared cell boundary, as would be seen with light microscopy.DOI:http://dx.doi.org/10.7554/eLife.02893.023
Mentions: Our results thus far suggest that gradients of Ds and Fj expression, by producing asymmetric orientation of Ft-Ds heterodimers, provide directional information to bias core protein polarization. Given the apparent variation in asymmetry of Ft-Ds dimers at different times and places in wing development, we wished to assess the potential consequences of this variation on core PCP protein asymmetry. We therefore simulated this mechanism by adapting our previously described mathematical model for PCP signaling (Amonlirdviman et al., 2005; Ma et al., 2008). The modified model establishes a MT network with polarity determined by the relative concentrations of Ft on any side of a cell. User-defined input gradients of Ds and Fj determine Ft concentrations in a manner consistent with the experimentally defined model. Dsh is then transported toward the plus ends of MTs, while still permitting bulk movement of all components by diffusion (see Supplementary file 1). We first validated the model by correctly reproducing the domineering non-autonomy (or lack thereof) surrounding clones of core PCP mutants (Figure 5—figure supplement 1). Furthermore, we confirmed that the model correctly simulates the ability of the core module to propagate polarization across small ft mutant clones (Figure 5—figure supplement 1).

Bottom Line: Consistent with previous results, we find that the Ft/Ds/Fj-module has an effect on a MT-cytoskeleton.We show Ft/Ds/Fj-dependent initial polarization of the apical MT-cytoskeleton prior to global alignment of the core-module, reveal that the anchoring of apical non-centrosomal MTs at apical junctions is polarized, observe that directional trafficking of vesicles containing Dsh depends on Ft, and demonstrate the feasibility of this model by mathematical simulation.Together, these results support the hypothesis that Ft/Ds/Fj provides a signal to orient core PCP function via MT polarization.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, United States matism@uni-muenster.de.

Show MeSH
Related in: MedlinePlus