The Fat-Dachsous (Ft-Ds) pathway is a highly conserved system that coordinates planar polarity in epithelial tissues. This thesis examines the interplay between the Ft-Ds pathway and cell mechanics in the Drosophila melanogaster pupal wing as an example of how biochemical and mechanical signals are integrated in development.
By first exploring the cell behaviours in ft, ds, and dachs mutants through live imaging, I show that orientation of cell division, orientation of T1 transitions, and cell shapes are controlled by the Ft-Ds pathway from 16-18 hours after puparium formation (16-18 h APF). I also performed acute manipulation experiments to attempt to abrogate Ft and Ds function by cleaving off their intracellular domains, which altered the cell shapes. However, its effects on cell division orientation were, at best, weak.
I investigate how tissue tension from a process called wing hinge contraction affects cellular behaviours and the Ft-Ds pathway from 20-22 h APF. The results presented in this thesis suggest a tug-of-war takes place between the Ft-Ds pathway and tissue tension in controlling the orientation of cell division in the pupal wing.
Using genetic tools and laser ablation, I alter the forces within the pupal wing in vivo and study its effects on the stability of Ft-EGFP. Ft-EGFP becomes more stable at junctions under tension, suggesting that Ft may be mechanosensitive. Moreover, the loss of Dachs (a known downstream effector of Ft) stabilises Ft-EGFP, hinting that Dachs may have a mechanical feedback role in the Ft-Ds pathway.
Finally, I build a two-dimensional vertex model that incorporates Ft-Ds planar polarity dynamics and cell divisions that I hope other researchers can build on to further understand Drosophila pupal wing morphogenesis.
