Figure 1.
Fat (Ft)-Dachsous (Ds)-Four-jointed (Fj) system regulates PCP in Drosophila wing.
(A) Schematic of Drosophila wing showing opposing expression gradients of Ds (green) and Fj (grey) while expression of Ft (not shown) remains uniform. Arrow marks the proximal-distal (P/D) axis of the wing. (B) Arrangement of cells (boxes) seen in the contexts of proximo distally increasing gradient of Fj expression (grey) as well its activity; the latter represented by arrows and hammers symbolizing its activating and repressive roles, respectively, while thicknesses of these lines indicate relative strengths of these activities. (C) Different concentrations of the Ft-Ds heterodimer (represented by thickness of red line) at the proximal and distal edges of the cells provide distinct intensity plot. (C′) A line joining the peaks of these two levels of Ft-Ds heterodimer at the proximal and distal edges would be proximally or distally inclined depending on the concentrations of the Ft-Ds heterodimer at these edges. This line would, however, be horizontally placed when concentrations of the Ft-Ds heterodimer are equal at the proximal and distal edges. (C′′) Simplified visual representations of the concentrations of Ft-Ds heterodimer at the proximal and distal edges of the epithelial cells seen in (C′). (D) Orientation of wing hairs in wild type and in dachsous (ds) mutant adult wings.
Figure 2.
Evolution of phosphorylated Ft (Ftp) and phosphorylated Ds (Dsp).
(A–D) Evolution of sub-cellular concentrations of phosphorylated Ft () and that of (E–H) phosphorylated Ds (
) in cells over time. (A) and (E) show the randomized initial concentrations of
and
, respectively.
Table 1.
List of parameters used in the theoretical model.
Figure 3.
Evolution of asymmetric localization of the Ft-Ds heterodimer in cells over time.
(A–H) Evolution of the asymmetric levels of Ft-Ds heterodimer in cells. (A) shows the initial uncoordinated levels of Ft-Ds heterodimer while that shown in (H) represent the final steady state.
Figure 4.
Fj gradient, but not that of Ds, is essential for generating the asymmetric localization of the Ft-Ds heterodimer.
(A) Asymmetric localization of Ft-Ds heterodimer (distally heightened top of trapezoid) is seen when both- Fj and Ds are expressed in gradient. Data shown here is the same as that shown in Figure 3H. (B) Uniform over-expression of Fj results in a loss of asymmetry of Ft-Ds heterodimer (flattened top) in all cells, although Ds expression is maintained in a gradient. (C) Conversely, uniform overexpression of Ds does not affect Ft-Ds heterodimer asymmetry when Fj expression remains in a gradient. (D) When both Fj and Ds are uniformly overexpressed, asymmetry of Ft-Ds heterodimer is lost.
Figure 5.
Phosphorylation of Ft by Fj kinase is necessary for Ft-Ds asymmetry.
(A) Wild type Fj activity displays characteristic distal enrichment of Ft-Ds heterodimers. Data shown here is same as that shown in Figure 3H. Inset displays the ordered projection of Drosophila wing hair in proximal-distal axis. Arrow and hammer indicate the activating and repressing roles of kinase Fj against Ft and Ds, respectively. (B) Asymmetry of Ft-Ds heterodimer is disrupted when phosphorylation of Ft by Fj kinase is lost in Fj(Ft) mutant. This would result in swirling of wing hairs (inset). (C) Loss of kinase activity of Fj against Ds in Fj(Ds) mutant, however, does not influence asymmetric localization of Ft-Ds heterodimer. Orientations of wing hairs now remain intact (inset) like that of wild type wing (A).
Figure 6.
Sub-cellular asymmetry of enriches asymmetry of Ft-Ds heterodimer.
(A) Equal contributions of sub-cellular asymmetries of and
result in asymmetric localization of Ft-Ds heterodimer (µ = 1). Inset shows the enlarged view with inclined tops of the trapezoids. Data shown here is same as that shown in Figure 3H. (B) Higher contribution of sub-cellular asymmetry of
augments the asymmetric localization of Ft-Ds heterodimer (steeper top of the trapezoids) in cells (µ = 10). (C) Higher contribution of
sub-cellular asymmetry, however, results in diminished or even reversed asymmetry of Ft-Ds heterodimer in cells (µ = 0.1). Inset shows the enlarged view with flatter tops of the trapezoids indicating weak asymmetry of Ft-Ds heterodimer.