The mechanisms that order cellular packing geometry are critical for the functioning of many tissues, but are poorly understood. Here we investigate this problem in the developing wing of Drosophila. The surface of the wing is decorated by hexagonally packed hairs that are uniformly oriented towards the distal wing tip. They are constructed by a hexagonal array of wing epithelial cells. We find that wing epithelial cells are irregularly arranged throughout most of development but become hexagonally packed shortly before hair formation. During the process, individual cell junctions grow and shrink, resulting in local neighbor exchanges. These dynamic changes mediate hexagonal packing and require the efficient delivery of E-cadherin to remodeling junctions; a process that depends on both the large GTPase Dynamin and the function of Rab11 recycling endosomes. We suggest that E-cadherin is actively internalized and recycled as wing epithelial cells pack into a regular hexagonal array. Hexagonal packing furthermore depends on the activity of the Planar Cell Polarity proteins. The Planar Cell Polarity group of proteins coordinates complex and polarized cell behavior in many contexts. No common cell biological mechanism has yet been identified to explain their functions in different tissues. A genetic interaction between Dynamin and the Planar Cell Polarity mutants suggests that the planar cell polarity proteins may modulate Dynamin-dependent trafficking of E-cadherin to enable the dynamic remodeling of junctions. We furthermore show that the Planar Cell Polarity protein Flamingo can recruit the exocyst component Sec5. Sec5 vesicles also co-localizes with E-cadherin and Flamingo. Based on these observations we propose that during the hexagonal repacking of the wing epithelium these proteins polarize the trafficking of E-cadherin-containing exocyst vesicles to remodeling junctions. The work presented in this thesis shows that one of the basic cellular functions of planar cell polarity signaling may be the regulation of dynamic cell adhesion. In doing so, the planar cell polarity pathway mediates the acquisition of a regular packing geometry of Drosophila wing epithelial cells. We identify polarized exocyst-dependent membrane traffic as the first basic cellular mechanism that can explain the role of PCP proteins in different developmental systems.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:swb:14-1157034530833-40169 |
| Date | 31 August 2006 |
| Creators | Classen, Anne-Kathrin |
| Contributors | Technische Universität Dresden, Biologie, Dr. Suzanne Eaton, Prof. Dr. Michael Brand, Prof. Dr. Elizabeth Knust, Dr. Suzanne Eaton |
| Publisher | Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis |
| Format | application/pdf |
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