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Interplay between mechanical tension and cytoskeletal organization in cell separation at compartment boundaries in Drosophila

Subject Area Developmental Biology
Cell Biology
Term from 2015 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 273663197
 
The formation of straight lineage restrictions (compartment boundaries) between cells of different fates or functions is an important strategy of animal development to pattern tissues. The straightness of compartment boundaries in proliferating and morphogenetically active tissues is challenged by cell intercalations that lead to cell intermingling. Cell junctions along compartment boundaries are characterized by a local increase of mechanical tension as compared to cell junctions in the bulk of the tissue. Computer simulations indicate that this local increase in cell bond tension results in a bias of junctional rearrangements during cell intercalations that maintains the straight alignment of cell junctions along compartment boundaries. However, how mechanical tension is increased at cell junctions along compartment boundaries and whether the local increase in mechanical tension is required to bias junctional rearrangements and thus to maintain the characteristically straight compartment boundary shape remains unknown.The compartment boundary separating anterior and posterior cells of the Drosophila pupal abdominal epidermis is a useful system to analyze the mechanisms underlying compartment boundaries. Cells in this tissue are amenable to live imaging, genetic manipulation, and force measurements. In the current funding period of the SPP1782, we have shown that increased mechanical tension at this compartment boundary can be separated into an initiation phase and a maintenance phase. The initiation phase, when the first junctions between anterior and posterior cells are formed, correlates with elevated levels of F-actin and non-muscle Myosin II and is independent of transcriptional regulation. During the maintenance phase, non-muscle Myosin II is no longer elevated, but increased mechanical tension depends on transcription. This proposal has two aims. First, to analyze the mechanisms by which mechanical tension is increased during the initiation phase. To achieve this aim, we will analyze the subcellular trafficking and recruitment of Myosin II motor proteins using a combination of genetics and live imaging. Second, to analyze the requirement of increased mechanical tension to bias cell rearrangement during cell intercalations and thus to maintain the straight compartment boundary shape. To achieve this aim, we will use an optogenetic method to locally decrease mechanical tension at cell junctions along the compartment boundary.We expect that our results will provide novel insights into the mechanisms by which mechanical tension at cell junctions is regulated and by which this regulation influences cell behavior during tissue development.
DFG Programme Priority Programmes
 
 

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